Method for obtaining a liquid biological sample from an extracorporeal circuit for extracorporeal blood purification treatment, and related devices and systems

Abstract

The present invention relates to a method for obtaining a liquid biological sample from an extracorporeal circuit for performing an extracorporeal blood purification treatment on a patient (101), said method comprising a sampling phase, in which: I) a first sampling port (131) of said extracorporeal circuit is in fluid communication with a first collection chamber (151) via a first hydraulic machine (141), said first sampling port (131) being operatively connected to a first blood line (111) input to a hemodia filter (115) of said extracorporeal circuit; II) a second sampling port (132) of said extracorporeal circuit is in fluid communication with a second collection chamber (152) via a second hydraulic machine (142), said second sampling port (132) being operatively connected to a second blood line (112) output from said hemodia filter (115); III) a third sampling port (133) of the extracorporeal circuit is in fluid communication with a third collection chamber (153) via a third hydraulic machine (143), the third sampling port (133) being operatively connected to a drain line (113) of the hemodiafilter (115), the method being characterized in that the first hydraulic machine (141) fills the first collection chamber (151) with a first biological sample (A), the second hydraulic machine (142) fills the second collection chamber (152) with a second biological sample (B), and the third hydraulic machine (143) fills the third collection chamber (153) with a third biological sample (C), and the first hydraulic machine (141), the second hydraulic machine (142) and the third hydraulic machine (143) are activated simultaneously at a flow rate value (P).

Description

[Technical field]

[0001] The present invention relates to a method for obtaining a liquid biological sample from an extracorporeal circuit for performing an extracorporeal blood purification treatment on a patient according to the preamble of claim 1. In particular, described herein is a method for obtaining a liquid biological sample from an extracorporeal circuit for performing an extracorporeal blood purification treatment on a patient, an apparatus for obtaining the liquid biological sample, an apparatus for analyzing the obtained liquid biological sample, and corresponding systems. [Background technology]

[0002] The present invention may be used to monitor one or more parameters of a patient and / or an extracorporeal treatment being performed on the patient, such as blood concentration of solutes, achieved clearance values, and / or sieving coefficient values. The present invention may be used for extracorporeal blood purification treatments, such as haemodialysis (HD), haemofiltration (HF), and haemodiafiltration (HDF). In particular, the present invention may be used for intensive care dialysis treatments, such as Continuous Renal Replacement Therapy (CRRT), Continuous Artero Venous Haemofiltration (CAVH), and Continuous Veno Venous Haemofiltration (CVVH), which are frequently used in intensive care settings to support the kidney function of patients suffering from acute kidney injury. Such CRRT, CAVH, and CVVH treatments apply continuous extracorporeal treatment to the patient's blood tissue using an extracorporeal blood purification machine. Similar to a patient's physiological renal function, such treatment allows the removal of waste solutes and substances through an artificial semipermeable hemodiafiltration membrane in the hemodiafilter of the extracorporeal circuit. Solutes can pass through such membranes by concentration differences (diffusive clearance), by pressure differences (convective clearance), and by direct absorption.

[0003] The amount of clearance required as a result of such a dialysis treatment specifies the concept of clearance dose. Just like the medication dose, which represents the posology, the clearance dose defines the amount of clearance that should be obtained for a given solute in a dialysis treatment. Clearance, i.e. the amount of blood cleared of a substance per unit of time, is a solute-dependent concept that is primarily related to the capacity of the hemodiafiltration membrane to pass a solute, for example due to a concentration or pressure gradient. This phenomenon depends on the ratio between the molecular size of the solute and the pore size of the membrane; generally, the larger the size of the solute, the lower the capacity of the solute to pass through the pores of the hemodiafiltration membrane and therefore the lower the probability of elimination of such solute from the patient's blood.

[0004] In particular, the volume of solutes passing through the hemodiafiltration membrane and then eliminated with the waste fluid generated by the treatment is so dramatically and unexpectedly reduced during treatment that the purification dose, i.e., clearance, actually achieved for the patient is systematically different from the prescribed purification dose. This phenomenon affects solute removal depending on the size of the solute, and is more pronounced for larger solutes that are generally more difficult to pass through the hemodiafiltration membrane. The reason for such reduced transmembrane clearance can be summarized in a concept known as membrane fouling, a stochastic process in which multiple phenomena, including protein membrane adhesion and local coagulation activation, significantly reduce the transmembrane passage of solutes that need to be removed from the patient's blood tissue.

[0005] The resulting involuntary undertreatment can adversely affect the patient's clinical status to such an extent that careful and frequent monitoring of realized clearance (i.e., current effective realized dose) is now strongly recommended by the Acute Dialysis Quality Initiative (ADQI), the most authoritative international scientific organization in the field.

[0006] Techniques currently known in the art for measuring the achieved clearance require at least one manual collection of blood and waste fluid, also called effluent, samples from predefined points of the extracorporeal circuit according to specific procedures; and such biological samples must be sent to a laboratory for quantification of the concentration of the solute under test, i.e. urea, traditionally chosen as the solute representative of uremic retention during acute kidney failure.

[0007] Techniques currently known in the art for measuring achieved clearance suffer from several drawbacks, examples of which are listed below.

[0008] A first drawback results from the fact that such a technique is extremely complex: in fact, a proper biological sampling procedure requires three medical professionals working together to manually take two blood samples and one drainage liquid sample from the extracorporeal circuit, for example with a syringe. In such situations, there is often a high biological risk for the medical professionals and also a high risk of sampling errors that may invalidate the entire evaluation process. Moreover, in intensive care settings, where space is small and personnel are lacking in numbers, it is often not possible to involve three different professionals in the sampling process.

[0009] A second drawback stems from the fact that the concentration values ​​of the solute under test are generally not available in real time, but approximately 4-6 hours after collection. In fact, the acquired biological sample must be sent to an analytical laboratory for quantification of the solute under test according to non-standard operating procedures. Such procedures often lack correct transmission of the request to the analytical laboratory, which may be confused due to the receipt of several different biological samples and the nature of the sample of the effluent liquid, which does not correspond to either blood or urine. As a result, further interaction with the laboratory is often necessary to clarify the nature of the request, thus further extending the response time and increasing the organizational engagement required of the medical personnel. This only allows a retrospective evaluation of the achieved clearance. However, it is known that the dynamic correction of the prescribed purification dose aimed at adjusting the extracorporeal clearance to the actual metabolic demand of the patient requires that the achieved clearance be monitored substantially in real time.

[0010] A further drawback results from the fact that urea is considered as the only solute to be evaluated for measuring the realized clearance, so the results obtained therein can only be consistent with solutes having a molecular weight similar to that of urea, i.e. of the order of a few Daltons. However, it is known that the target of CRRT treatment in the intensive care setting consists mainly of medium to large solutes, such as myoglobin or circulating blood cytokines. As a result, the measurements of the effective realized clearance dose obtained using urea do not represent the extracorporeal clearance of the target solutes of the dialysis treatment.

[0011] Yet another drawback lies in the fact that calculation of the achieved clearance requires the use of complex mathematical models, which are often unknown to the medical personnel performing the sampling and requesting the analysis, implying a higher risk of error in the assessment of the achieved clearance.

[0012] In light of the above observations regarding the complexity of the sampling process, the long time required for sending samples and performing laboratory analysis, and the complexity of the mathematical calculations required, the effective realized clearance dose is not usually quantified during clinical practice at present, despite recommendations, and quantifying extracorporeal clearance only for urea limits the information obtained to solutes having a molecular size similar to that of such solutes. Summary of the Invention

[0013] It is therefore an object of the present invention to solve these and other problems of the prior art, and in particular to provide a method, acquisition device, analysis device and system for acquiring a liquid biological sample from an extracorporeal circuit for subjecting a patient to an extracorporeal blood purification treatment, which allows for automating the sampling process while reducing its complexity and increasing its safety.

[0014] Another object of the present invention is to provide a method, acquisition device, analysis device and system for acquiring a liquid biological sample from an extracorporeal circuit for subjecting a patient to an extracorporeal blood purification treatment, which makes it possible to obtain the results necessary to calculate the extracorporeal clearance in real time, or in any case in less time than in the prior art.

[0015] It is a further object of the present invention to provide a method, acquisition device, analysis device, and system for acquiring a liquid biological sample from an extracorporeal circuit for administering extracorporeal blood purification treatment to a patient, which allows for quantification of extracorporeal clearance for two or more solutes having molecular sizes equal to or greater than that of urea.

[0016] Briefly, the present invention relates to the automated acquisition of liquid biological samples from an extracorporeal circuit for administering extracorporeal blood purification treatment to a patient, with automated real-time determination of extracorporeal clearance values ​​for solutes having small, medium, and large molecular weights.

[0017] Advantageous features of the invention are set forth in the appended claims, which form an integral part of this specification. [Brief description of the drawings]

[0018] The present invention will now be described in detail through some non-limiting exemplary embodiments thereof with particular reference to the accompanying drawings. [Figure 1] 1 is a schematic diagram of a system for obtaining a liquid biological sample from an extracorporeal circuit for performing an extracorporeal blood purification treatment on a patient, according to one embodiment of the present invention. [Diagram 2] FIG. 2 is an exemplary block diagram of an analytical device of the system of FIG. 1. [Diagram 3] 2 is an exemplary flow chart of a method for obtaining a liquid biological sample from an extracorporeal circuit for subjecting a patient to an extracorporeal blood purification treatment, according to an embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0019] 1, there is shown a system 100 for obtaining a fluid biological sample from an extracorporeal circuit for performing an extracorporeal blood purification treatment on a patient 101. The system 100 comprises a hemodialysis machine 110, an apparatus for obtaining a fluid biological sample 140, and an extracorporeal circuit, operatively connected to each other.

[0020] Additionally, the system 100 may include an analysis device 200 for analyzing the biological sample acquired by the acquisition device 140 .

[0021] The hemodialysis machine 110, for example a CRRT (Continuous Renal Replacement Therapy) device, comprises a hemodiafilter 115 consisting of a first compartment and a second compartment separated from each other by an artificial semi-permeable hemodiafiltration membrane. The blood tissue of the patient 101 under treatment flows in the first compartment, while either a saline solution of suitable composition and concentration, called dialysis liquid (or dialysate), or a waste liquid (effluent) flows in the second compartment. In the hemodiafilter 115, the regulation of the blood concentration of solutes occurs by the transmembrane passage of said solutes between the blood tissue and the dialysate, according to the physical principle of a concentration gradient that tends to balance the concentrations between the blood tissue and the dialysate. It is also possible to force the transmembrane passage of the liquid and the solutes dissolved therein through a suitable regulation of the transmembrane pressure gradient in the hemodiafilter 115. The hemodiafiltration membrane may be, for example, of cellulose or synthetic derivatives.

[0022] The hemodialysis machine 110 comprises a first pump (not shown in FIG. 1 ) that provides circulation of blood tissue from the patient 101 to the hemodiafilter 115 via a first blood line 111 input to the hemodiafilter 115; the first pump also provides circulation of blood tissue from the hemodiafilter 115 to the patient 101 via a second blood line 112 output from the hemodiafilter 115. For example, the first blood line 111 and the second blood line 112 may comprise flexible and / or rigid tubing made from silicone, rubber, or PVC, while the first pump may comprise a peristaltic pump.

[0023] Furthermore, the hemodialysis machine 110 comprises a second pump (not shown in FIG. 1 ) that provides circulation of dialysate from a first tank 120 with clean dialysate to the hemodiafilter 115 via an inflow line 114 input to the hemodiafilter 115; the second pump also provides circulation of dialysate from the hemodiafilter 115 to a second tank 121 with discharged dialysate via a drain line 113 output from the hemodiafilter 115. For example, the inflow line 114 and the drain line 113 may comprise flexible and / or rigid tubing made from silicone, rubber, or PVC, while the second pump may comprise a peristaltic pump.

[0024] The extracorporeal circuit comprises a hemodiafilter 115, a first blood line 111 (inflow blood line), a second blood line 112 (outflow blood line), an inflow line 114, a drain line 113, a vascular access, e.g., a needle or catheter, and tubing and accessories for circulation of blood tissue and dialysate within the hemodiafilter 115. In particular, the extracorporeal circuit comprises a first circuit comprising a first compartment of the hemodiafilter 115, the first blood line 111, and the second blood line 112; furthermore, the extracorporeal circuit comprises a second circuit comprising a second compartment of the hemodiafilter 115, the inflow line 114, and the drain line 113.

[0025] The first and second circuits are separated from each other by a semi-permeable hemodiafiltration membrane.

[0026] According to the present invention, the device 140 for obtaining a liquid biological sample may include a first hydraulic machine 141, a second hydraulic machine 142, and a third hydraulic machine 143, each of which may comprise, for example, an electrically operable peristaltic pump; the device 140 further comprises a first collection chamber 151, a second collection chamber 152, and a third collection chamber 153.

[0027] The first collection chamber 151 is adapted to be fluidly connected with the first sampling port 131 of the extracorporeal circuit, for example via a first hydraulic machine 141 which may be operably connected to the first sampling port 131 via a first connecting line 116; the first sampling port 131 is operably connected to a first blood line 111 input to the hemodialysis filter 115.

[0028] The second collection chamber 152 is adapted to be fluidly connected with the second sampling port 132 of the extracorporeal circuit, for example via a second hydraulic machine 142 which may be operably connected to the second sampling port 132 via a second connecting line 117; the second sampling port 132 is operably connected to the second blood line 112 output from the hemodialysis filter 115.

[0029] For example, the third collection chamber 153 is adapted to be fluidly connected to the third sampling port 133 of the extracorporeal circuit via a third hydraulic machine 143 which may be operably connected to the third sampling port 133 via a third connecting line 118; the third sampling port 133 is operably connected to the drain line 113 of the hemodia filter 115.

[0030] The first connecting line 116, the second connecting line 117, and the third connecting line 118 may include flexible and / or rigid tubing made from, for example, silicone, rubber, or PVC.

[0031] For example, the first collection chamber 151, as well as the second collection chamber 152 and the third collection chamber 153, may be made from a plastic or glassy material and may have a volume V in the range of 0.1 ml to 2 ml.

[0032] In particular, the first collection chamber 151, as well as the second collection chamber 152 and the third collection chamber 153, may include at least one opening through which a substance in a liquid state, such as blood tissue or dialysis fluid of the patient 101, can enter and / or exit; the opening may include a lid adapted to hermetically seal the first collection chamber 151. In one embodiment of the invention, a needle and / or a cannula may be hermetically inserted into the lid and may be in fluid communication with the first sampling port 131. For example, the lid may be made of an elastic material suitable for sealing the first collection chamber 151, such as rubber and / or silicone. The same examples of embodiments described above with reference to the first collection chamber 151 also apply mutatis mutandis to the second collection chamber 152 and the third collection chamber 153. In one embodiment of the invention, each of the first collection chamber 151, the second collection chamber 152, and the third collection chamber 153 may be individually removable from the device 140, independent of the other collection chambers 151, 152, 153. Additionally, the first collection chamber 151, the second collection chamber 152, and the third collection chamber 153 may be either disposable or, alternatively, reusable, for example, after a sterilization process.

[0033] Additionally or alternatively, storage unit 150 may include first collection chamber 151, second collection chamber 152, and third collection chamber 153, where storage unit 150 may be removable from device 140 for acquisition of a liquid biological sample. For example, first collection chamber 151, second collection chamber 152, and third collection chamber 153 may be housed on a plastic support of storage unit 150 that is suitably shaped to allow access to a needle and / or cannula contained in the lid of each of first collection chamber 151, second collection chamber 152, and third collection chamber 153.

[0034] Thus, according to the present invention, the first hydraulic machine 141 is adapted to fill the first collecting chamber 151 with a first biological sample A, the second hydraulic machine 142 is adapted to fill the second collecting chamber 152 with a second biological sample B, and the third hydraulic machine 143 is adapted to fill the third collecting chamber 153 with a third biological sample C. In particular, the first biological sample A may comprise a sample of blood tissue coming from the first blood line 111 input to the hemodia filter 115, the second biological sample B may comprise a sample of blood tissue coming from the second blood line 112 output from the hemodia filter 115, and the third biological sample C may comprise a sample of the discharged dialysate coming from the drain line 113 output from the hemodia filter 115.

[0035] Advantageously, according to the invention, the first hydraulic machine 141, the second hydraulic machine 142 and the third hydraulic machine 143 may be activated at the flow rate value P simultaneously.

[0036] For example, the first hydraulic machine 141, the second hydraulic machine 142 and the third hydraulic machine 143 may be electrically controlled by a control unit of the device 140, the control unit for example activating them simultaneously for the sampling time interval T. For example, the first hydraulic machine 141, the second hydraulic machine 142 and the third hydraulic machine 143 may be activated simultaneously upon receiving an electrical command signal generated by a medical professional using a sampling start button included in the device 140. The flow rate value P may for example be in the range of 0.1 ml / min to 2 ml / min for each of the first hydraulic machine 141, the second hydraulic machine 142 and the third hydraulic machine 143 and may be set via the control means of the first hydraulic machine 141, the second hydraulic machine 142 and the third hydraulic machine 143. Consequently, the sampling time interval T can be determined based on the flow rate value P and volume V of each of the first collection chamber 151, the second collection chamber 152, and the third collection chamber 153, for example according to the following relationship: T=V / P, expressed in minutes.

[0037] Advantageously, the device 140 for the acquisition of liquid biological samples according to the invention makes it possible to sample a first biological sample A, a second biological sample B and a third biological sample C with a much higher accuracy than can be obtained with the currently known manual method involving three medical professionals. Furthermore, advantageously, the device 140 for the acquisition of liquid biological samples according to the invention ensures a significant reduction in the biological risk posed by medical personnel carrying out said manual method.

[0038] 2 shows an exemplary block diagram of an analytical device 200 for analyzing a first biological sample A, a second biological sample B, and a third biological sample C according to this embodiment of the present invention. The analytical device 200 may include actuator means 210, sensor means 220, interface means 230, memory means 240, and processing means 250, which may be interconnected using a communication bus 201.

[0039] The actuator means 210 is adapted to perform physical and / or chemical operations on at least one of the first biological sample A, the second biological sample B, and the third biological sample C in the analysis device 200.

[0040] For example, the actuator means 210 may perform at least one of the following physical and / or chemical operations: handling, centrifugation, division, heating and cooling, mixing with one or more chemicals. Furthermore, the actuator means 210 may perform an analytical method on at least one of said first biological sample A, second biological sample B, and third biological sample C in the analytical device 200. In particular, the actuator means 210 may perform one or more of the following analytical methods: immunofluorescence, colorimetric, UV, electrochemical, immunoturbidimetric, and potentiometric. The actuator means 210 may include one or more of the following devices: electromechanical servomechanism, electric servomotor, automated gripping arm, electric pump, UV lamp, IR lamp, LASER light source, cooling device, and heating device.

[0041] The sensor means 220 is adapted to measure one or more physical quantities relating to at least one of said first biological sample A, second biological sample B, third biological sample C and any further samples that may be obtained therefrom. The sensor means 220 may include one or more of the following sensors: inertial measurement unit (IMU), gyroscope, accelerometer, altimeter, thermometer, barometer, piezoelectric sensor, extensometer, load cell, voltmeter, ammeter, spectrometer, pH meter.

[0042] The interface means 230 is adapted to operatively couple an operator for managing and configuring the analysis device 200. The interface means 230 may include, for example, a keyboard, a screen, a touch screen, a mouse device, and the like.

[0043] Furthermore, the interface means 230 may comprise communication means enabling communication between the analysis device 200 and a server (not shown in FIG. 2 ). The communication means may include, for example, an Ethernet interface, a WiFi interface, a USB interface, a mobile network interface (GSM, UMTS, LTE, 5G), etc.

[0044] The memory means 240 is adapted to store information and instructions for the analysis device 200 .

[0045] Such information may include data and / or parameters relating to the actuator means 210, the sensor means 220, and the interface means 230. The instructions stored in the memory means 240 are described in more detail below with reference to the flow chart of Figure 3. The memory means 240 may include, for example, a flash type solid state memory.

[0046] The processing means 250 is adapted to process information and instructions related to the interface means 230, the sensor means 220 and the actuator means 210 stored in the memory means 240 and may include, for example, a multi-core ARM processor, a microcontroller, etc. The communication bus 201 is adapted to interconnect said memory means 240, the interface means 230, the sensor means 220 and the actuator means 210 with the processing means 250.

[0047] According to the present invention, the actuator means 210, the interface means 230, the sensor means 220, the memory means 240 and the processing means 250 are adapted to perform all operations necessary to analyze a first biological sample A, a second biological sample B and a third biological sample C.

[0048] In particular, the actuator means 210 is adapted to receive a first collection chamber 151 with a first biological sample A, a second collection chamber 152 with a second biological sample B, and a third collection chamber 153 with a third biological sample C. For example, said first collection chamber 151, second collection chamber 152, and third collection chamber 153 may be accommodated one by one in an inlet of the analysis device 200, for example comprising an inlet box or an inlet slot. Alternatively, said first collection chamber 151, second collection chamber 152, and third collection chamber 153 may be accommodated collectively and simultaneously in an inlet of the analysis device 200, for example using a storage unit 150 comprising said first collection chamber 151, second collection chamber 152, and third collection chamber 153. In particular, the storage unit 150 can be introduced into the analytical device 200 and then removed from the analytical device 200 upon completion of the analysis of a first biological sample A, a second biological sample B, and a third biological sample C.

[0049] Furthermore, the actuator means 210 is adapted to further divide each of the first biological sample A, the second biological sample B and the third biological sample C into at least a first share A1, B1, C1, a second share A2, B2, C2 and a third share A3, B3, C3. For example, each biological sample A, B, and C may be taken in equal volumes from each of the first collection chamber 151, the second collection chamber 152, and the third collection chamber 153 and poured into at least two or more test tubes, for example made of glass, of the analytical device 200, so that each of the first shares A1, B1, C1, the second shares A2, B2, C2, and the third shares A3, B3, C3 may be analyzed by the sensor means 220 according to one or more of the following methods: immunofluorescence, colorimetric, UV, electrochemical, immunoturbidimetric, and potentiometric. In particular, the first shares A1, B1, C1 may relate to a first solute having a first molecular weight value between 0 and 500 Daltons, while the second shares A2, B2, C2 may relate to a second solute having a second molecular weight value between 501 and 5,000 Daltons, and finally the third shares A3, B3, C3 may relate to a third solute having a third molecular weight value between 5,001 and 100,000 Daltons. The table below shows one example of possible first, second and third solutes that can be analyzed by the analysis device 200 according to the invention. [Table 1] For example, the methods of analysis listed in Table 1 may be performed simultaneously on the first shares A1, B1, C1, the second shares A2, B2, C2, and the third shares A3, B3, C3.

[0050] Furthermore, following the analyses listed above, the sensor means 220 is adapted to determine, for each of the first shares A1, B1, C1, the second shares A2, B2, C2, and the third shares A3, B3, C3, concentration values ​​of the first solutes C_A1, C_B1, C_C1, the second solutes C_A2, C_B2, C_C2, and the third solutes C_A3, C_B3, C_C3, for example expressed in mg / l. For example, such concentration values ​​C_A1, C_B1, C_C1, C_A2, C_B2, C_C2, C_A3, C_B3, and C_C3 can be determined via the sensor means 220 according to one or more of the following methods: immunofluorescence, colorimetry, UV, electrochemical, immunoturbidimetry, and potentiometry.

[0051] The processing means 250 is adapted to determine a first mass balance error Err1, a second mass balance error Err2 and a third mass balance error Err3 based on at least one of the concentration values ​​C_A1, C_B1, C_C1 of the first solute, the concentration values ​​C_A2, C_B2, C_C2 of the second solute and the concentration values ​​C_A3, C_B3, C_C3 of the third solute. In particular, the first mass balance error Err1 is related to the first solute, the second mass balance error Err2 is related to the second solute and the third mass balance error Err3 is related to the third solute. For example, the first mass balance error Err1, the second mass balance error Err2 and the third mass balance error Err3 may be expressed as percentages and determined according to the following relationship:

[0052]

number

[0053]

number

[0054] Further, the processing means 250 is adapted to determine clearance values ​​K1, K2, K3 and / or sieving coefficients H1, H2, H3 for each of said first solute, second solute and third solute when each of said first mass balance error Err1, second mass balance error Err2 and third mass balance error Err3 is comprised between -10% and +10%.

[0055] For example, such clearance values ​​K1, K2, and K3 may be determined according to the following relationships:

number

[0056] For example, such concentration values ​​C_A1, C_B1, C_A2, C_B2, C_A3, and C_B3 may be determined via the sensor means 220 according to one or more of the following methods: immunofluorescence, colorimetric, UV, electrochemical, immunoturbidimetric, and potentiometric.

[0057] In particular, Qb denotes a blood flow value expressed in ml / min, while Quf denotes an ultrafiltration flow value that can be determined as: Quf = Qr_pre + Qr_post + Qnet, where Qr_pre is a pre-dilution substitution flow value expressed in ml / h, Qr_post is a post-dilution substitution flow value expressed in ml / h, and Qnet is a net ultrafiltration flow value expressed in ml / h. Such values ​​of Qr_pre, Qr_post, Qnet and Qb can be obtained from the hemodialysis machine 110 during the hemodialysis process.

[0058] Advantageously, according to the invention, the clearance values ​​K1, K2, K3 can be calculated as: I) instantaneous clearance values ​​of solutes with different molecular weights, i.e. small, medium, large (see Table 1); II) the variation of such clearance values ​​over time; III) currentDose = Qr_pre + Qr_post + Qnet + Qd, where Qd is the dialysate flow rate value, expressed in ml / h, obtainable from the hemodialysis machine 110 during the hemodialysis process, allowing to directly evaluate the variation of such clearance values ​​measured for the solutes (current effective realized dose) compared to the clearance estimated from the drainage flow rate (current dose). It is also possible to evaluate in a simple and instantaneous way how the variations of the prescription of the flow rates Qr_pre, Qr_post, Qnet and Qb of the hemodialysis machine 110 affect the actual clearance of the various target solutes.

[0059] Additionally or alternatively, the processing means 250 is adapted to determine sieving coefficients H1, H2, H3 for each of said first solute, second solute, and third solute, which may be determined according to the following relationships:

number

[0060] Advantageously, according to the invention, the sieving coefficients H1, H2, H3 make it possible to evaluate the fouling effect on the hemodiafiltration membrane, for example by means of image comparison in which such sieving coefficients H1, H2, H3 obtainable from different measurement values ​​taken at different time intervals are superimposed.

[0061] It will be clear to the skilled person that, according to the present invention, for the purpose of determining one or more additional clearance values ​​and / or one or more sieving coefficients, one or more additional solutes may be considered in addition to the first solute, the second solute, and the third solute. Advantageously, this allows a more effective evaluation of the fouling effect on the hemodiafiltration membrane. Such one or more additional solutes may have a molecular weight value in the range of 0 to 100,000 Daltons.

[0062] According to the present invention, the analytical device 200 may be replaced by two or more devices that together perform the operations required to analyze the first biological sample A, the second biological sample B, and the third biological sample C as known in the art and previously described herein with reference to the analytical device 200. For example, the first device may further divide each of the first biological sample A, the second biological sample B, and the third biological sample C into a first share A1, B1, C1, a second share A2, B2, C2, and a third share A3, B3, C3. The second device may then separately analyze the first share A1, B1, C1, the second share A2, B2, C2, and the third share A3, B3, C3 to obtain a first mass balance error Err1, a second mass balance error Err2, and a third mass balance error Err3 according to the relationship 1). Finally, the third device may determine clearance values ​​K1, K2, K3 and / or sieving coefficients H1, H2, H3 for each of the first solute, second solute and third solute, for example according to relationships 3) and 4), respectively, when each of the first mass balance error Err1, second mass balance error Err2 and third mass balance error Err3 is comprised between -10% and +10%.

[0063] A method for obtaining a liquid biological sample from an extracorporeal circuit for subjecting a patient 101 to an extracorporeal blood purification treatment will be described below with reference to FIG.

[0064] In step 300, an initialization phase is performed in which the hemodialysis machine 110 and the device for obtaining a liquid biological sample 140 are operatively connected to the extracorporeal circuit, for example by a medical professional. During this phase, the medical professional may initialize both the hemodialysis machine 110 and the device for obtaining a liquid biological sample 140 for administering a hemodialysis treatment to the patient 101.

[0065] During this phase, a medical professional may initialize the analytical device 200, for example, by subjecting it to a sterilization process.

[0066] In step 310, a sampling phase is performed, in which a first sampling port 131 of the extracorporeal circuit is in fluid communication with a first collection chamber 151 via a first hydraulic machine 141 of the acquisition device 140; in particular, the first sampling port 131 is operatively connected to a first blood line 111 input to a hemodia filter 115 of the extracorporeal circuit. A second sampling port 132 of the extracorporeal circuit is in fluid communication with a second collection chamber 152 via a second hydraulic machine 142 of the acquisition device 140; in particular, the second sampling port 132 is operatively connected to a second blood line 112 output from the hemodia filter 115. A third sampling port 133 of the extracorporeal circuit is fluidly connected to a third collection chamber 153 via a third hydraulic machine 143 of the acquisition device 140; in particular, the third sampling port 133 is operably connected to the drain line 113 of the hemodia filter 115.

[0067] During this phase, the first hydraulic machine 141 fills the first collection chamber 151 with a first biological sample A, while the second hydraulic machine 142 fills the second collection chamber 152 with a second biological sample B and the third hydraulic machine 143 fills the third collection chamber 153 with a third biological sample C. Advantageously, the first hydraulic machine 141, the second hydraulic machine 142 and the third hydraulic machine 143 are activated simultaneously with a flow rate value P, which may for example preferably be in the range of 0.1 ml / min to 2 ml / min and which may be set via the control means of said first hydraulic machine 141, the second hydraulic machine 142 and the third hydraulic machine 143.

[0068] During this phase, for example, the first hydraulic machine 141, the second hydraulic machine 142 and the third hydraulic machine 143 may be electronically controlled, for example by a control unit of the device 140, the control unit comprising a control unit which activates them simultaneously for the sampling time interval T.

[0069] For example, the first hydraulic machine 141, the second hydraulic machine 142, and the third hydraulic machine 143 may be activated simultaneously upon receiving an electrical command signal generated by a medical professional using a sampling start button included in the device 140. As a result, the sampling time interval T may be determined, for example, based on the flow rate value P and the volume V of each of the first collection chamber 151, the second collection chamber 152, and the third collection chamber 153, for example, according to the following relationship: T=V / P, expressed in minutes.

[0070] Advantageously, the device 140 for the acquisition of liquid biological samples according to the invention makes it possible to sample a first biological sample A, a second biological sample B and a third biological sample C with a much higher accuracy than can be obtained with the currently known manual method involving three medical professionals. Furthermore, advantageously, the device 140 for the acquisition of liquid biological samples according to the invention ensures a significant reduction in the biological risk posed by medical personnel carrying out said manual method.

[0071] According to the present invention, the following steps may be further carried out:

[0072] In step 320, a phase of analyzing the first biological sample A, the second biological sample B, and the third biological sample C is performed. For example, the first biological sample A, the second biological sample B, and the third biological sample C may be simultaneously extracted from the acquisition device 140 if contained in the storage unit 150 and then transferred to the analysis device 200. Alternatively, the first biological sample A, the second biological sample B, and the third biological sample C may be transferred individually, one by one, to the analysis device 200. During this phase, each of the first biological sample A, the second biological sample B, and the third biological sample C is further divided into at least a first share A1, B1, C1, a second share A2, B2, C2, and a third share A3, B3, C3, where the first share A1, B1, C1 is related to a first solute having a first molecular weight value of 0-500 Daltons, the second share A2, B2, C2 is related to a second solute having a second molecular weight value of 501-5,000 Daltons, and the third share A3, B3, C3 is related to a third solute having a third molecular weight value of 5,001-100,000 Daltons. For example, each biological sample A, B, and C can be taken in equal volumes from each of the first collection chamber 151, the second collection chamber 152, and the third collection chamber 153, and then poured into two or more test tubes, for example made of glass, of the analysis device 200, so that each of the first shares A1, B1, C1, the second shares A2, B2, C2, and the third shares A3, B3, C3 can be analyzed via the sensor means 220 according to one or more of the following methods: immunofluorescence, colorimetric, UV, electrochemical, immunoturbidimetric, and potentiometric. During this stage, concentration values ​​of the first solute C_A1, C_B1, C_C1, concentration values ​​of the second solute C_A2, C_B2, C_C2 and concentration values ​​of the third solute C_A3, C_B3, C_C3 are determined for each of the first shares A1, B1, C1, second shares A2, B2, C2 and third shares A3, B3, C3, for example using the above mentioned methods of analysis.For example, each of the concentration values ​​C_A1, C_B1, C_C1 of the first solute, C_A2, C_B2, C_C2 of the second solute and C_A3, C_B3, C_C3 of the third solute are determined via the sensor means 220 according to one or more of the following methods: immunofluorescence, colorimetric, UV, electrochemical, immunoturbidimetric, potentiometric.

[0073] In step 330, a first processing phase is performed in which a first mass balance error Err1, a second mass balance error Err2, and a third mass balance error Err3 are determined based on at least one of the concentration values ​​C_A1, C_B1, C_C1 of the first solute, the concentration values ​​C_A2, C_B2, C_C2 of the second solute, and the concentration values ​​C_A3, C_B3, C_C3 of the third solute; the first mass balance error Err1 is related to the first solute, the second mass balance error Err2 is related to the second solute, and the third mass balance error Err3 is related to the third solute. For example, the first mass balance error Err1, the second mass balance error Err2, and the third mass balance error Err3 may be expressed as percentages and determined according to the relationships 1) and 2).

[0074] In step 340, the processing means 250 verify whether each of the first mass balance error Err1, the second mass balance error Err2, and the third mass balance error Err3 is between −10% and +10%. If so, they execute step 350, otherwise they execute step 345.

[0075] In step 345, the interface means 230 issues an error message to alert the operator that the first mass balance error Err1, the second mass balance error Err2, and the third mass balance error Err3 each exceed 5% in absolute value. For example, the error message may be displayed on the screen of the interface means 230. Then, step 360 is executed.

[0076] In step 350, a second processing phase is performed in which clearance values ​​K1, K2, K3 and / or sieving coefficients H1, H2, H3 are determined for each of the first solute, second solute, and third solute, e.g., according to relationships 2) and 3), respectively.

[0077] In step 360, the processing means 250 executes a termination phase, in which all operations necessary to terminate the method according to the invention are performed. For example, during this phase the first mass balance error Err1, the second mass balance error Err2 and the third mass balance error Err3 may be stored in the memory means 240 and / or displayed by the medical personnel on the screen of the interface means 230. Furthermore, the clearance values ​​K1, K2, K3 and / or the sieving coefficients H1, H2, H3 may be stored in the memory means 240 and / or displayed by the medical professional on the screen of the interface means 230. For example, at the end of this phase the analysis device 200 may execute all operations necessary to clean and / or sterilize the actuator means 210 and the sensor means 220.

[0078] One or more phases of the method described above with reference to FIG. 3 may be implemented, for example, using a computer program product comprising portions of software code that may be loaded into the memory of a terminal, such as, for example, a computer, a tablet, a Raspberry PI unit, etc., such terminal being usable to control the acquisition device 140 and / or the analysis device 200.

[0079] Advantageously, according to the invention, the clearance values ​​K1, K2, K3 allow: I) instantaneous clearance values ​​of solutes with different molecular weights, i.e. small, medium and large (see Table 1); II) the variation of such clearance values ​​over time; III) the direct evaluation of the variation of such clearance values ​​measured for solutes (current effective realized dose) compared to the clearance estimated from the effluent flow rate (current dose). Also advantageously, according to the invention, the sieving coefficients H1, H2, H3 allow the evaluation of the fouling effect on the hemodiafiltration membrane, for example by means of image comparison, where such sieving coefficients H1, H2, H3 obtainable from different measurements taken at different time intervals are superimposed.

[0080] The advantages of the present invention are apparent from the above description.

[0081] The present invention provides a method, acquisition device, analysis device, and system for acquiring a liquid biological sample from an extracorporeal circuit for performing an extracorporeal blood purification treatment on a patient, which advantageously allows for automating the process of sampling the biological sample using a first hydraulic machine, a second hydraulic machine, and a third hydraulic machine that can be activated simultaneously at one flow rate value.

[0082] Another advantage of the present invention lies in the fact that it provides a method, an acquisition device, an analysis device and a system for acquiring a liquid biological sample from an extracorporeal circuit for subjecting a patient to an extracorporeal blood purification treatment, which advantageously allows quantifying the extracorporeal clearance for two or more solutes having a molecular size equal to or larger than that of urea. Indeed, advantageously, the clearance values ​​obtained according to the present invention allow a direct assessment of the instantaneous clearance of solutes with different molecular weights (small, medium and large), the variation of said clearance values ​​over time, the variation of said clearance values ​​measured for a solute (current effective realized dose) compared to the clearance estimated from the drainage flow rate (current dose).

[0083] A further advantage of the present invention derives from the fact that the present invention provides a method, acquisition device, analysis device and system for acquiring a liquid biological sample from an extracorporeal circuit for subjecting a patient to an extracorporeal blood purification treatment, which advantageously allows for extracorporeal clearance to be obtained in real time, or in any case in less time than in the prior art, since the biological sample acquired in accordance with the above description of the invention can be easily handled and easily analyzed by an operator.

[0084] Naturally, without prejudice to the principles of the invention, the form and implementation details of the embodiments may be modified significantly from what has been described and illustrated herein purely as non-limiting examples, but without departing from the scope of protection of the invention as set forth in the appended claims. (Other possible items) [Item 1] A method for obtaining a liquid biological sample from an extracorporeal circuit for performing an extracorporeal blood purification treatment on a patient (101), the method comprising a sampling phase, wherein: I) a first sampling port (131) of the extracorporeal circuit is in fluid communication with a first collection chamber (151) via a first hydraulic machine (141), the first sampling port (131) being operatively connected to a first blood line (111) input to a hemodiafiltration filter (115) of the extracorporeal circuit; II) a second sampling port (132) of the extracorporeal circuit is in fluid communication with a second collection chamber (152) via a second hydraulic machine (142), the second sampling port (132) being operatively connected to a second blood line (112) outputting from the hemodiafilter (115); III) a third sampling port (133) of the extracorporeal circuit is in fluid communication with a third collection chamber (153) via a third hydraulic machine (143), the third sampling port (133) being operatively connected to a drain line (113) of the hemodia filter (115); The method is characterized in that the first hydraulic machine (141) fills the first collection chamber (151) with a first biological sample (A), the second hydraulic machine (142) fills the second collection chamber (152) with a second biological sample (B), and the third hydraulic machine (143) fills the third collection chamber (153) with a third biological sample (C), and the first hydraulic machine (141), the second hydraulic machine (142), and the third hydraulic machine (143) are activated simultaneously at a flow rate value (P). [Item 2] - an analysis phase, in which each of said first biological sample (A), second biological sample (B) and third biological sample (C) is further divided into at least a first share (A1, B1, C1), a second share (A2, B2, C2) and a third share (A3, B3, C3), respectively, wherein said first share (A1, B1, C1) is related to a first solute having a first molecular weight value between 0 and 500 Daltons and said second share (A2, B2, C2) is related to a second solute having a second molecular weight value between 501 and 5,000 Daltons; and said third shares (A3, B3, C3) relate to a third solute having a third molecular weight value of 5,001 to 100,000 Daltons, wherein a concentration value (C_A1, C_B1, C_C1) of said first solute, a concentration value (C_A2, C_B2, C_C2) of said second solute, and a concentration value (C_A3, C_B3, C_C3) of said third solute are determined for each of the first shares (A1, B1, C1), second shares (A2, B2, C2), and third shares (A3, B3, C3); - a first processing phase, in which a first mass balance error (Err1), a second mass balance error (Err2) and a third mass balance error (Err3) are determined based on at least one of the concentration values ​​of the first solute (C_A1, C_B1, C_C1), the concentration values ​​of the second solute (C_A2, C_B2, C_C2) and the concentration values ​​of the third solute (C_A3, C_B3, C_C3), wherein the first mass balance error (Err1) is related to the first solute, the second mass balance error (Err2) is related to the second solute and the third mass balance error (Err3) is related to the third solute; a second processing phase, in which clearance values ​​(K1, K2, K3) and / or sieving coefficients (H1, H2, H3), or effluent saturation coefficients are determined for each of the first, second, and third solutes when each of the first mass balance error (Err1), the second mass balance error (Err2), and the third mass balance error (Err3) is comprised between -10% and +10%; The method of claim 1, comprising: [Item 3] 3. The method of claim 2, wherein each of the concentration values ​​of the first solute (C_A1, C_B1, C_C1), the second solute (C_A2, C_B2, C_C2), and the third solute (C_A3, C_B3, C_C3) is determined according to one or more of the following methods: immunofluorescence, colorimetric, UV, electrochemical, immunoturbidimetric, and potentiometric. [Item 4] An apparatus (140) for obtaining a liquid biological sample from an extracorporeal circuit for performing an extracorporeal blood purification treatment on a patient (101), the apparatus (140) comprising a first hydraulic machine (141), a second hydraulic machine (142) and a third hydraulic machine (143); I) a first collection chamber (151) adapted to be in fluid communication with a first sampling port (131) of the extracorporeal circuit via the first hydraulic machine (141), the first sampling port (131) being operatively connected to a first blood line (111) input to a hemodiafiltration filter (115) of the extracorporeal circuit; II) a second collection chamber (152) adapted to be in fluid communication with a second sampling port (132) of the extracorporeal circuit via the second hydraulic machine (142), the second sampling port (132) being operatively connected to a second blood line (112) outputting from the hemodiafilter (115); III) a third collection chamber (153) adapted to be in fluid communication with a third sampling port (133) of the extracorporeal circuit via the third hydraulic machine (143), the third sampling port (133) being operatively connected to a drain line (113) of the hemodia filter (115); Equipped with The device (140) is characterized in that the first hydraulic machine (141) is adapted to fill the first collection chamber (151) with a first biological sample (A), the second hydraulic machine (142) is adapted to fill the second collection chamber (152) with a second biological sample (B), and the third hydraulic machine (143) is adapted to fill the third collection chamber (153) with a third biological sample (C), and the first hydraulic machine (141), the second hydraulic machine (142), and the third hydraulic machine (143) are simultaneously activatable at a flow rate value (P). [Item 5] 5. The acquisition device (140) of item 4, wherein the storage unit (150) comprises the first collection chamber (151), the second collection chamber (152), and the third collection chamber (153), and the storage unit (150) is removable from the device (140) for acquisition of a liquid biological sample. [Item 6] An analytical device (200), - receiving a first collection chamber (151) with a first biological sample (A), a second collection chamber (152) with a second biological sample (B), and a third collection chamber (153) with a third biological sample (C); - further dividing each of said first biological sample (A), second biological sample (B) and third biological sample (C) into at least a first share (A1, B1, C1), a second share (A2, B2, C2) and a third share (A3, B3, C3), respectively, said first share (A1, B1, C1) relating to a first solute having a first molecular weight value between 0 and 500 Daltons, said second share (A2, B2, C2) relating to a second solute having a second molecular weight value between 501 and 5,000 Daltons and said third share (A3, B3, C3) relating to a third solute having a third molecular weight value between 5,001 and 100,000 Daltons; - determining a concentration value of the first solute (C_A1, C_B1, C_C1), a concentration value of the second solute (C_A2, C_B2, C_C2), and a concentration value of the third solute (C_A3, C_B3, C_C3) for each of the first share (A1, B1, C1), second share (A2, B2, C2), and third share (A3, B3, C3); - determining a first mass balance error (Err1), a second mass balance error (Err2), and a third mass balance error (Err3) based on at least one of the concentration values ​​of the first solute (C_A1, C_B1, C_C1), the concentration values ​​of the second solute (C_A2, C_B2, C_C2), and the concentration values ​​of the third solute (C_A3, C_B3, C_C3), wherein the first mass balance error (Err1) is related to the first solute, the second mass balance error (Err2) is related to the second solute, and the third mass balance error (Err3) is related to the third solute; - determining the clearance values ​​(K1, K2, K3) and / or sieving coefficients (H1, H2, H3) or effluent saturation coefficients for each of the first solute, second solute, and third solute when each of the first mass balance error (Err1), second mass balance error (Err2), and third mass balance error (Err3) is comprised between -10% and +10%. The analytical device (200) comprises actuator means (210), sensor means (220), memory means (240), and processing means (250) adapted to: [Item 7] 7. The analytical device (200) of item 6, wherein each of the concentration values ​​of the first solute (C_A1, C_B1, C_C1), the second solute (C_A2, C_B2, C_C2), and the third solute (C_A3, C_B3, C_C3) can be determined according to one or more of the following methods: immunofluorescence, colorimetric, UV, electrochemical, immunoturbidimetric, and potentiometric. [Item 8] 8. The analytical device (200) of claim 6 or 7, wherein the storage unit (150) comprises the first collection chamber (151), the second collection chamber (152), and the third collection chamber (153), and the storage unit (150) is removable from the analytical device (200). [Item 9] A system (100) for obtaining a liquid biological sample from an extracorporeal circuit for performing an extracorporeal blood purification treatment on a patient (101), said system (100) comprising a machine for performing an extracorporeal blood purification treatment on a patient (101), a device (140) for obtaining a liquid biological sample according to one or more of items 4 and 5, and said extracorporeal circuit, operably connected to each other. [Item 10] 10. The system (100) according to item 9, comprising an analytical device (200) according to one or more of items 6 to 8.

Claims

1. 1. A method for obtaining a liquid biological sample from an extracorporeal circuit for performing an extracorporeal blood purification treatment on a patient, the method comprising a sampling phase, wherein: I) a first sampling port of the extracorporeal circuit is in fluid communication with a first collection chamber via a first hydraulic machine, the first sampling port being operably connected to a first blood line input to a hemodialysis filter of the extracorporeal circuit; II) a second sampling port of the extracorporeal circuit is in fluid communication with a second collection chamber via a second hydraulic machine, the second sampling port being operably connected to a second blood line output from the hemodia filter; III) a third sampling port of the extracorporeal circuit is in fluid communication with a third collection chamber via a third hydraulic machine, the third sampling port being operably connected to a drain line of the hemodia filter; a first hydraulic machine filling the first collection chamber with a first biological sample, a second hydraulic machine filling the second collection chamber with a second biological sample, and a third hydraulic machine filling the third collection chamber with a third biological sample, wherein the first hydraulic machine, the second hydraulic machine, and the third hydraulic machine are activated simultaneously at a flow rate value.

2. an analysis phase, in which each of the first biological sample, the second biological sample, and the third biological sample is further divided into at least a first share, a second share, and a third share, respectively, where the first share is related to a first solute having a first molecular weight value between 0 and 500 Daltons, the second share is related to a second solute having a second molecular weight value between 501 and 5,000 Daltons, and the third share is related to a third solute having a third molecular weight value between 5,001 and 100,000 Daltons, and where a concentration value of the first solute, a concentration value of the second solute, and a concentration value of the third solute are determined for each of the first share, the second share, and the third share; a first processing phase, in which a first mass balance error, a second mass balance error, and a third mass balance error are determined based on at least one of the concentration value of the first solute, the concentration value of the second solute, and the concentration value of the third solute, the first mass balance error relating to the first solute, the second mass balance error relating to the second solute, and the third mass balance error relating to the third solute; a second processing phase, in which a clearance value and / or a sieving coefficient, or an effluent saturation coefficient, is determined for each of said first solute, second solute and third solute when each of said first mass balance error, second mass balance error and third mass balance error is comprised between -10% and +10%; The method of claim 1 , comprising:

3. 3. The method of claim 2, wherein each of the concentration values ​​of the first solute, the second solute, and the third solute is determined according to one or more of the following methods: immunofluorescence, colorimetric, UV, electrochemical, immunoturbidimetric, and potentiometric.

4. 1. An apparatus for obtaining a liquid biological sample from an extracorporeal circuit for performing an extracorporeal blood purification treatment on a patient, the apparatus comprising: a first hydraulic machine, a second hydraulic machine, and a third hydraulic machine; I) a first collection chamber adapted to be in fluid communication with a first sampling port of the extracorporeal circuit via the first hydraulic machine, the first sampling port being operably connected to a first blood line input to a hemodialysis filter of the extracorporeal circuit; II) a second collection chamber adapted to be in fluid communication with a second sampling port of the extracorporeal circuit via the second hydraulic machine, the second sampling port being operatively connected to a second blood line output from the hemodia filter; III) a third collection chamber adapted to be in fluid communication with a third sampling port of the extracorporeal circuit via the third hydraulic machine, the third sampling port being operably connected to a drain line of the hemodia filter; Equipped with the first hydraulic machine is adapted to fill the first collection chamber with a first biological sample, the second hydraulic machine is adapted to fill the second collection chamber with a second biological sample, and the third hydraulic machine is adapted to fill the third collection chamber with a third biological sample, and the first hydraulic machine, the second hydraulic machine, and the third hydraulic machine are simultaneously activatable at a flow rate value.

5. The device of claim 4 , wherein a storage unit includes the first collection chamber, the second collection chamber, and the third collection chamber, the storage unit being removable from the device for acquisition of a liquid biological sample.

6. There is an analytical device, - receiving a first collection chamber with a first biological sample, a second collection chamber with a second biological sample, and a third collection chamber with a third biological sample; - further dividing each of said first biological sample, second biological sample, and third biological sample into at least a first share, a second share, and a third share, respectively, said first share relating to a first solute having a first molecular weight value between 0 and 500 Daltons, said second share relating to a second solute having a second molecular weight value between 501 and 5,000 Daltons, and said third share relating to a third solute having a third molecular weight value between 5,001 and 100,000 Daltons; - determining a concentration value of the first solute, a concentration value of the second solute, and a concentration value of the third solute for each of the first share, the second share, and the third share; - determining a first mass balance error, a second mass balance error, and a third mass balance error based on at least one of the concentration value of the first solute, the concentration value of the second solute, and the concentration value of the third solute, wherein the first mass balance error is related to the first solute, the second mass balance error is related to the second solute, and the third mass balance error is related to the third solute; - determining a clearance value and / or a sieving coefficient or a effluent saturation coefficient for each of said first solute, second solute and third solute when each of said first mass balance error, second mass balance error and third mass balance error is comprised between -10% and +10%; 4. An analytical apparatus comprising actuator means, sensor means, memory means and processing means adapted to:

7. 7. The analytical device of claim 6, wherein each of the concentration values ​​of the first solute, the second solute, and the third solute can be determined according to one or more of the following methods: immunofluorescence, colorimetric, UV, electrochemical, immunoturbidimetric, and potentiometric.

8. The analytical device of claim 6 , wherein a storage unit includes the first collection chamber, the second collection chamber, and the third collection chamber, and wherein the storage unit is removable from the analytical device.

9. 6. A system for obtaining a liquid biological sample from an extracorporeal circuit for performing an extracorporeal blood purification treatment on a patient, the system comprising: a machine for performing an extracorporeal blood purification treatment on a patient; a device for obtaining a liquid biological sample according to claim 4 or 5; and the extracorporeal circuit, operably connected to each other.

10. A system according to claim 9, comprising an analytical device according to any one of claims 6 to 8.

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