Pressure measurement in an extracorporeal blood circuit

Abstract

The present invention relates to a method for calibrating a first pressure sensor (PA), which measures a first pressure in a liquid-filled hose (1) in the form of a force signal, is directly attached to the hose and integrated into a first clamping fixture for correcting a drift signal caused by the hose by means of a correction function with a pressure reference signal obtained by a first pressure reference sensor (PHOP). The method comprises the following steps: a) performing a recursive analysis and prediction on at least one correction function to find a correction signal for correcting the drift signal by means of a corresponding pressure reference signal measured by the first pressure reference sensor at a constant internal pressure and a constant internal temperature in the hose; b) performing a first calibration on the force signal measured by the first pressure sensor and corrected by means of the correction signal by using the pressure reference signal measured by the first pressure reference sensor before the hose is effectively used; c) performing a second calibration on the force signal measured by the first pressure sensor and corrected by means of the correction signal by using the pressure reference signal measured by a second pressure reference sensor (PV) during the effective use of the hose. The present invention also relates to a device designed for applying such a method.

Description

Technical Field

[0001] The present disclosure relates to a method and a device for calibrating a pressure measurement value or a force sensor measurement value, which is used to determine the internal tube pressure in an extracorporeal circuit, so as to use a correction signal to correct the measurement value determined by the pressure measurement when using a force sensor directly applied to / adjacent to / abutting on the filling tube. Background Art

[0002] Generally speaking, the internal tube pressure can be measured by means of a pressure measurement pipeline. The (first) tube whose internal pressure is to be measured is connected to a pressure measurement pipeline (second tube), and the pressure measurement pipeline then feeds the pressure to be measured to a (piezoelectric) pressure sensor / pressure transducer. For this purpose, the pressure measurement pipeline is connected to the (first) tube via a T-piece. The pressure sensor is preferably arranged at the upper (free) end of the pressure measurement pipeline by means of a Luer lock connection. Between the liquid column in the pressure measurement pipeline and the pressure transducer, there is an air cushion, and the air cushion will change (expand or contract) when the pressure in the (first) tube changes, which in turn causes a corresponding deflection of the pressure transducer.

[0003] Among other things, this pressure measurement method or measurement system has the following disadvantages: for example, in the case where blood or another air-oxidizable liquid communicating with the extracorporeal circuit flows through the (first) tube, fluid-air contact occurs inside the pressure measurement pipeline, the manufacturing and assembly costs of the tube increase due to the T-piece, and this measurement setup makes it more difficult to clean the pressure measurement pipeline. In addition, there is a risk of direct contact between the pressure sensor / pressure transducer and the liquid.

[0004] In order to avoid blood-air contact (for example, such blood-air contact is particularly disadvantageous in applications such as dialysis), so-called "pressure chambers" are used. For example, here, the pressure is not directly transmitted from the blood to the air cushion, but the blood and air are separated from each other by a flexible membrane. The change in the pressure inside the (first) tube deflects the membrane, and this force is transmitted to the pressure sensor via the air cushion adjacent to the membrane, and the pressure sensor measures the internal tube pressure. This means that also in this known design, the air cushion is set as the pressure transmission medium between the membrane and the pressure sensor, but direct contact between the air cushion and the fluid flowing in the (first) tube is avoided. This measurement setup also has the disadvantage of high manufacturing costs.

[0005] Thus, for example, in EP 1 357 372 A1, a clamping device is provided in which a (first) tube is clamped and the internal pressure of the (first) tube is to be measured. The internal tube pressure is measured non-invasively, i.e., by means of a force measurement via the tube outer wall rather than, for example, via a T-branch for the connection between the tube interior and the measurement sensor system. The tube expansion caused by the change in the internal tube pressure is transmitted via a force transmission device to a force sensor, which outputs a force signal. A proportionality factor is used to convert the change in the force signal proportionally into a pressure change. In the case of a pressure change, only the tube deformation at the gap of a support body extending longitudinally through the clamping device is evaluated to generate the force signal.

[0006] However, the viscoelastic behavior of the tube must be taken into account when measuring the internal tube pressure via a clamping device. This means that when the tube is clamped, a restoring force / recovery force is generated in the form of a drift signal, which is superimposed on the force signal or pressure signal to be measured. In the case of a longer measurement time, the effect of the restoring force is such that even under constant conditions, the internal pressure in the (first) tube appears to decrease. To solve this problem, it has hitherto been assumed that the pressure signal can be corrected by using ambient air as a reference. This means that the viscoelastic behavior is investigated by filling the tube with air before it is effectively used. Then, during effective use, the resulting reset signal is subtracted from the displayed pressure change process (in a tube filled with a liquid such as blood). However, a tube filled with a medium / liquid behaves differently from a tube filled with air. Therefore, a pressure signal using ambient air as a reference does not give an indication of the pressure signal of the filled tube (filled with a fluid).

[0007] To be able to correct such a distorted pressure signal, document DE 197 47 254 C2 provides a method for correcting a pressure signal measured via a clamping device according to the foregoing description. For this purpose, the course of the restoring force is represented in the form of a relaxation function, which is tube-related and pre-known (determined). The parameters of this function are determined based on the measured force signal. With the help of this relaxation function, the force signal can be corrected and the pressure signal can be determined via a linear relationship with the force signal. Summary of the Invention

[0008] Against this background, the object of the present invention is to further improve the correction of the force signal and to correct the drift signal caused by the mechanical properties of the (first) tube using a reference signal before and during the effective use of the (first) tube (the effectively used tube means, for example, a tube connected to a patient or a tube during treatment). In addition, the relative pressure change and the absolute internal tube pressure should preferably be determined with a pressure accuracy of ±10 mmHg.

[0009] This object is solved by the method according to claim 1 and the device according to claim 10. Advantageous embodiments of the invention are the subject matter of the dependent claims.

[0010] Accordingly, the present invention provides a method for calibrating a first force sensor / first pressure sensor, which measures the first pressure, in particular the arterial pressure, in a (first) tube filled with a liquid (the tube being a dialyzer tube in an extracorporeal (blood) circuit) in the form of a force signal. The pressure sensor is directly adjacent to the (first) tube / is directly adjacent to the (first) tube and is integrated into / inserted into a first clamping device so as to correct the drift signal caused by the (first) tube by using a calibration function independent of the tube parameters with a pressure reference signal obtained by a first (separate) pressure reference sensor. According to the present invention, the following steps are performed:

[0011] a) Performing a regression analysis and prediction on a calibration function independent of at least one tube parameter for finding a calibration signal for correcting the drift signal achieved by clamping the tube within the first clamping device by using the corresponding pressure reference signal measured by the first pressure reference sensor at a constant internal tube pressure and at a constant internal tube temperature;

[0012] b) Performing a first calibration on the force signal measured by the first force sensor and corrected by using the calibration signal by using the pressure reference signal measured by the first pressure reference sensor before the effective use of the tube, wherein the tube is connected to a patient during the effective use of the tube; and

[0013] c) Performing a second calibration on the force signal measured by the first force sensor and corrected by using the (previously predicted) calibration function by using the pressure reference signal measured by a second (separate) pressure reference sensor during the effective use of the tube.

[0014] In other words, a method for online calibration of force-pressure signals is provided, which is applied to the filled (first) tube before and during the effective use (first) tube according to the present invention. This means that, first, a first calibration is performed on the (test / simulation) force signal generated by the first force sensor by using the pressure reference signal determined by using a pressure reference sensor and a calibration function independent of the tube parameters before the effective use of the (first) tube. Then, during the effective use of the tube, a second calibration is performed on the (second) force signal that has been corrected by using the calibration function based on the pressure reference signal preferably generated by the second pressure reference sensor.

[0015] Specifically, a mathematical correction function and two-point calibration are applied in such a way that absolute pressure measurement becomes possible. The pressure measurement is carried out via a force sensor integrated in the clamping device. The mathematical correction function is determined at a constant internal tube pressure and a constant internal tube temperature, preferably within a few minutes after the (first) tube is inserted into the clamping device, based on the measured (text) force-pressure signal and a reference pressure, which is determined via a (separate) pressure reference sensor (which has a different combination of settings and / or mounting compared to the force sensor) and provides a drift signal. The pressure reference sensor preferably has a higher measurement accuracy compared to the corresponding pressure / force sensor. Then, a first calibration is performed, during which the internal tube pressure and the internal tube temperature are constant while obtaining the pressure / force signals for determining the correction function. In a subsequent recalibration (second calibration), the (first) tube is subjected to a constant known pressure, and the correction function is determined again based on the pressure data measured during this period. Thus, this reference method includes calibration procedures before and during the effective use of the tube, i.e., the reference method is carried out before and during the (dialysis) treatment of the patient.

[0016] This method allows pressure measurement via a clamping device directly located on the filled (first) tube as part of the tube system. With this type of pressure measurement, there is no longer a need for the Luer lock connectors used in the prior art in the area of the clamping device. This results in a reduction in the manufacturing cost of the tube system and an improvement in usability. The improved usability of the tube system is due to fewer connectors to be connected compared to conventional systems, and thus machines using this tube system can be upgraded faster, the frequency of leaks is lower, and the tube system is designed more clearly. In addition, this tube system has the advantage of reducing or avoiding air contact with the tube fluid. In the case where the fluid flowing through the (first) tube is blood, the risk of blood coagulation is reduced. Therefore, less anticoagulant has to be added to the blood, thereby reducing the treatment cost. In addition, the machine-side pressure connectors (Luer lock connectors) do not wear out, and the risk of contamination caused by pressure measurement is suppressed.

[0017] However, the main advantage of the method according to the invention is that the reference measurement during the effective use of the (first) tube provides significantly more accurate values compared to a separate reference measurement before the effective tube use. The correction function determined in the method according to the invention can be carried out independently of the tube material or tube size and can therefore also be generally used for unknown tube systems.

[0018] The method can be configured in such a way that, in addition to the first pressure, a second pressure measured by a second force sensor / second pressure sensor integrated in the second clamping device, in particular the dialyzer inlet pressure, can also be measured and corrected. Thus, the force signal of the second force sensor is calibrated in the first calibration and the second calibration using the pressure reference signal measured by the second pressure reference sensor. In this way, the internal tube pressure can be measured and corrected at two different points in the extracorporeal circuit without fluid-air contact.

[0019] An advantageous embodiment of the method according to the invention, which can be claimed independently, provides that the (first) tube (for example, the extracorporeal blood tube of a dialysis machine or a blood pump) comprises an arterial part (blood inlet part) and a venous part (blood outlet part). The first and / or second pressure / force sensor and the first pressure reference sensor are preferably arranged at the arterial part. The second pressure reference sensor is arranged on the venous part. The second pressure reference sensor can be a pressure / force sensor for checking the internal tube pressure in the venous part. The second pressure reference sensor (as the only one) is a conventional pressure sensor that is not integrated into the clamping device and does not generate a drift signal. This means that the pressure in the venous part of the (first) tube is preferably measured via the (as the only one) second pressure reference sensor, for example via a T-piece or a flexible membrane (with higher precision), according to the conventional pressure measurement method. This means that the (as the only one) second pressure reference sensor is further preferably connected to the machine to which the (first) tube is connected via a Luer lock connection. Thus, reference is made via the pressure reference sensor, which is more expensive than the sensor integrated in the clamping device but has higher precision. The first pressure reference sensor is arranged in the region of the arterial tube part and preferably has a piezoelectric element for pressure measurement.

[0020] Furthermore, it can be provided that a constant internal tube pressure can be achieved by adjusting the pumping ratio between the first pump and the second pump, where the first pump is in particular a blood pump and the second pump is in particular a dialysate inlet flow pump and / or a dialysate outlet flow pump. It is particularly reliable and simple to generate a constant pressure in the tube by adjusting the pumping ratio between these two pumps. For the method according to the invention, a constant pressure in the filled tube is crucial.

[0021] Furthermore, the method can be configured such that the drift signal is or corresponds to the restoring force of the clamped tube.

[0022] Furthermore, it is conceivable to convert the (corrected) force signal into a pressure signal via a linear recurrence using a corresponding pressure reference signal, or to calibrate the force signal using the pressure reference signal. This linear recurrence enables the pressure signal to be simply calculated from the corresponding force signal.

[0023] Another independently claimable embodiment provides that, in the case of using two force sensors, the first force sensor is arranged, in particular integrated, at the inlet opening / blood inlet of the first pump, and the second force sensor is arranged, in particular integrated, at the outlet opening / blood outlet of the first pump. Since in this case, the tube material, the temperature in the tube, and the time when the tube is inserted into the corresponding clamping device are the same at the positions of the force sensors, the expected drift behavior at the positions of the two force sensors should also be the same.

[0024] Furthermore, a device is provided, which has an extracorporeal circuit and at least one pressure / force sensor, in particular an arterial pressure / force sensor and / or a dialysate input pressure / force sensor, and the at least one pressure / force sensor is integrated in a clamping device for measuring the internal tube pressure in a fluid-filled tube having an arterial part and a venous part. In addition, the device includes at least one pressure reference sensor for referencing the pressure / force signal output by the at least one pressure sensor, in particular an arterial and / or venous force or pressure reference sensor. The at least one pressure reference sensor, in particular an arterial and / or venous pressure reference sensor, is not configured as a clamping device or not arranged to be integrated in a clamping device (without the configuration of a clamping device). In addition, the device preferably includes at least a first pump and a second pump. The device is provided and adapted to use a method for calibrating the pressure signal of the at least one pressure sensor using the reference signal of the at least one pressure reference sensor according to at least one aspect of the foregoing aspects of the present invention.

[0025] Finally, a calibration device is provided for calibrating the measurement of at least the first (internal) tube pressure, preferably arterial pressure. This first pressure is measured in the fluid circuit in the form of a force signal by a first force sensor / first pressure sensor / force sensor of the calibration device that is in direct contact with the tube or can be made in direct contact with the tube (on the outside), and the fluid circuit is in particular an extracorporeal (blood) circuit inside a tube filled with fluid / liquid / blood (not part of the device). The pressure / force sensor is integrated in the first clamping device. The first pressure is calibrated to correct the drift signal caused by the (first) tube (tube material) using a correction function independent of the tube parameters and the pressure reference signal acquired / generated by the first pressure reference sensor of the calibration device. The calibration device has the following units or parts:

[0026] a) A first computer part (CPU unit / program step), which is provided and adapted to analyze and predict at least one correction function for finding a correction signal for correcting the drift signal using the corresponding (force / ) pressure reference signal measured / generated by the first pressure reference sensor at a constant internal tube pressure and at a constant internal tube temperature;

[0027] b) A second computer part (CPU unit / program step), said second computer part being provided and adapted to perform a first calibration on the force signal measured by the first pressure / force sensor (PA) and then corrected using a correction signal, by means of the pressure reference signal measured / generated by the first pressure reference sensor, before the tube is operatively used; and

[0028] c) A third computer part (CPU unit / program step), said third computer part being provided and adapted to perform a second calibration on the force signal measured by the first pressure / force sensor and then corrected using a correction signal, by means of the (force / )pressure reference signal measured / generated by the second pressure reference sensor, during the effective (operative) use of the tube.

[0029] Two embodiments of the method according to the invention are described in detail below with reference to the accompanying drawings. Description of the Drawings

[0030] Figure 1 A diagram showing, by way of example, the course of the pressure in the clamping device over time;

[0031] Figure 2A A clamping device for clamping a tube;

[0032] Figure 2B A diagram showing the course of the drift signal relative to the reference signal;

[0033] Figure 3A The front part of a dialysis machine in a state before the effective use of the tube;

[0034] Figure 3B An alternative arrangement of two sensors;

[0035] Figure 4 A diagram showing the drift behavior of the tube in a closed clamping device;

[0036] Figure 5 A diagram showing the course of the drift signal and the correction function representing the drift behavior of the tube at a constant internal tube pressure;

[0037] Figure 6 A diagram showing graphically the determination of the pressure signal from the drift signal / force signal;

[0038] Figure 7 The front part of a dialysis machine during the effective use of the tube, with a patient connected to the machine;

[0039] Figure 8 A diagram showing an example of the course of the pressure change over time at the first pressure sensor during the execution of the method;

[0040] Figure 9 A diagram showing the pressure change process of a conventional pressure sensor, a first pressure reference sensor, and a first pump;

[0041] Figure 10A A diagram showing the simultaneous recording of the change process curve of two conventional pressure sensors and a second pressure reference sensor; Figure 10A A diagram showing the pressure change process of two conventional pressure sensors and a second pressure reference sensor recorded simultaneously with the change process curve of;

[0042] Figure 10B A diagram showing the time change process of the (simulated) blood flow rate and the blood pressure of a patient;

[0043] Figure 11A A diagram showing the deviation between the calculated pressure signal and the reference signal due to temperature drift;

[0044] Figure 11B A diagram related to the diagram in; Figure 11A showing the temperature change process of the fluid in the tube at the first pressure sensor and the second pressure sensor;

[0045] Figure 12A A diagram showing the deviation of the pressure signal of the second pressure reference sensor from the corresponding pressure reference signal and showing the linear correction signal;

[0046] Figure 12B A diagram related to the diagram in; Figure 12A showing the change process of the pressure signal and the pressure reference signal corrected by the linear correction signal;

[0047] Figure 13A A diagram showing the deviation of the pressure signal of the second pressure reference sensor from the corresponding pressure reference signal and the polynomial correction signal;

[0048] Figure 13B A diagram related to the diagram in; Figure 13A showing the change process of the pressure signal and the pressure reference signal corrected by the polynomial correction signal. DETAILED DESCRIPTION

[0049] The embodiments of the present disclosure will be described below based on the accompanying drawings. It should be noted that the shown figures are merely exemplary and not restrictive.

[0050] First Embodiment

[0051] General Method

[0052] Figure 1 An example of the pressure change process of a pressure sensor (here a PBE pressure sensor, which will be explained in more detail below) in millimeters of mercury (mmHg), where the time t is in seconds (s).

[0053] In stage 1, a tube is inserted into two clamping devices and the tube is filled with fluid. At least one pressure sensor is integrated into each of the two clamping devices and measures the pressure at the dialysis machine in the form of a force signal. The tube system is filled by changing the flow pump speed of at least one pump. During this stage, a leak test is also performed on the machine and the tube.

[0054] In stage 2, the pressure in the tube is kept constant. After a short stabilization phase, step a) as described above is performed for regression analysis and prediction of at least one correction function to find a correction signal for correcting the drift signal using the corresponding pressure reference signal. In step a), the correction function f is determined as a function of time t, where two constants a0, b are used for the viscoelastic behavior of the tube before treatment. The two constants a0 and b are determined using a mathematical method hereinafter referred to as "fitting". This method is explained below. With the help of this function, the drift signal in the form of a force signal of the corresponding pressure sensor is determined.

[0055] In stage 3, a pressure drop can be detected, which is used to correct the force signal using the correction function determined in step a). In addition, via the linear relationship between the reference signal and the corrected force signal, the corrected force signal of the pressure sensor is converted into a corrected pressure signal using the pressure reference signal of the correspondingly provided pressure reference sensor. The pressure reference sensor is a conventional pressure sensor. Thus, stage 3 shows the sequence of step b), which occurs before the start of treatment. In step b), the corrected force signal is calibrated before treatment using the pressure reference signal of the corresponding pressure reference sensor. Calibration can also be performed using a second constant pressure level.

[0056] A conventional pressure sensor is a pressure sensor that is not integrated into the clamping device and in which no restoring force affects the pressure signal. For a conventional pressure sensor, the internal tube pressure is determined, for example, via a T-piece or a pressure chamber or the like (as described above).

[0057] In stage 4, after a predetermined time after the start of treatment, preferably after 5 minutes, the newly corrected force signal is calibrated again using the pressure reference signal of the corresponding pressure reference sensor. Thus, in stage 4, step c) is performed.

[0058] In stage 5, the treatment process is shown, during which the PBE pressure remains substantially constant. It can be seen that the corrected PBE pressure signal and the reference signal are superimposed, which means that the correction of the pressure signal is sufficient and also works under varying pressures (see the time interval between approximately 2600 - 2700 s).

[0059] A clamping device used as a pressure sensor, the structure of a machine using the method according to the present invention, and steps a) to c) are described in detail below by way of example. In addition, alternative embodiments of the present invention are given below.

[0060] Background

[0061] Figure 2A A (first) tube 1 is shown, the internal pressure of which can be measured by a force sensor 2. For this purpose, the tube 1 is clamped in a clamping device 3. This (clamping device 3) clamps the tube 1, and the expansion or contraction of the tube 1 is transmitted to the force sensor 2 via a force transmission device 4. The change in the force that the force sensor 2 can measure is proportional to the change in the internal pressure in the tube 1.

[0062] Figure 2B A graph showing the pressure change process of the drift signal and the pressure change process of the reference signal over time is shown. The shown pressure signal / drift signal is the change process of the pressure in the tube 1 clamped in the clamping device 3 at time t0. Over the entire time curve shown, the value of the reference pressure is 0 mmHg (ambient pressure). The pressure signal shows an increase in pressure at time t0, and then the pressure change process decreases logarithmically, which can be explained by the restoring force of the tube. This drift signal must be subtracted from the actual measurement signal so that the absolute pressure equals the reference pressure.

[0063] Settings for performing the method according to the present invention

[0064] Figure 3A The front part of a dialysis machine 6 is shown, to which the (first) tube 1 is attached, the internal pressure of which will be measured at various points. The dialysis machine 6 has an extracorporeal circuit. The tube 1 has an arterial part / branch 1a and a venous part 1b. A first substitute port SP1 connects the arterial part 1a of the tube 1 to the machine 6, and a second substitute port SP2 connects the venous part 1b of the tube 1 to the machine 6. In the shown embodiment, the tube 1 is not connected to a patient, i.e., the tube is not in active use and is therefore in a pre-treatment state. Thus, the tube 1 is not filled with blood but with another fluid, which is a substitute (electrolyte fluid / eloat).

[0065] The fluid is first transported via the dialysate input flow pump FPE to the arterial tube section 1a, which is located on the outer front side of the dialysis machine 6. Before the fluid reaches the front of the dialysis machine 6, the first pressure reference sensor PHOP measures or obtains a reading of the internal tube pressure. The pressure reference sensor PHOP is thus also arranged at the substitute port SP and is an additional pressure sensor compared to the conventional dialysis machine 6. After the fluid enters the front of the dialysis machine 6, the fluid first passes through the arterial tube clamp SAKA, which is normally open. Then the fluid passes through the first clamping device (which is also referred to as the PA pressure sensor or the first pressure sensor PA), and thus through the first force sensor. The first clamping device is integrated in the front side of the dialysis machine 6. The PA sensor measures the pressure in the arterial section 1a of the tube 1. The pressure reference sensor PHOP can be used to reference the first pressure sensor PA, since the pressure reference sensor PHOP has a higher measurement accuracy compared to the first pressure sensor PA.

[0066] Then the fluid reaches the first pump, namely the blood pump BP, which continues to transport the fluid. Finally, the fluid passes through the second clamping device (which is also referred to as the PBE pressure sensor or the second pressure sensor PBE), and thus through the second force sensor. The PBE pressure sensor measures the dialysate inlet pressure at a point downstream of the blood pump BP along the direction of flow of the medium in the tube. Behind the PBE pressure sensor, the fluid can pass through the dialyzer 8. However, in the case of the bypass circuit via the bypass 10, the fluid can bypass the dialyzer instead of flowing through it. The venous tube section 1b is located behind the dialyzer / bypass along the direction of fluid flow. At a point downstream of the dialyzer / bypass and upstream of the air trap / deaerator 12 (in which the air trapped in the fluid is removed from the fluid), the fluid in the venous tube section 1b passes through a conventional pressure transducer, which is referred to as the PV measurement point. The conventional pressure transducer can be, for example, a T-piece or a pressure chamber.

[0067] After the PV measurement point, the fluid passes through the deaerator 12, then through the air detector 14, and finally through the normally open venous tube clamp SAKV. The venous tube clamp SAKV and the arterial tube clamp SAKA are only closed in the event of a fault and block the patient access during treatment. For example, such an error can be that the air detector detects an air volume greater than a certain threshold. After the fluid has passed through the venous tube clamp SAKV, the fluid flows out via the pump outlet of the dialysate output flow pump FPA through the substitute port SP2, which is arranged on the outer front side of the dialysis machine 6.

[0068] In addition, Figure 3AIt shows that a dialysis machine 6 is connected to a CPU having a first computer part, a second computer part, and a third computer part. Here, the CPU can control a dialysis fluid input flow pump FPE, a dialysis fluid output flow pump FPA, a pressure reference sensor PHOP, a pressure reference sensor PV, a first pressure sensor PA, a second pressure sensor PBE, a blood pump BP, an arterial tube clamp SAKA, and a venous tube clamp SAKV.

[0069] Figure 3B It shows an alternative arrangement of the blood pump BP and the first pressure sensor PA and the second pressure sensor PBE. In this case, the first (arterial) pressure sensor PA is directly located at the blood inlet of the blood pump BP, and the second (dialyzer inlet) pressure sensor PBE is directly located at the blood outlet of the blood pump BP. In this case, both the pressure sensors PA and PBE are integrated into the blood pump BP, and the tube material, the temperature of the tube, and the insertion time of both the pressure sensors PA and PBE are the same. The expected drift behaviors of the two pressure sensors PA and PBE are also the same. Therefore, the pressure difference P PBE -P A can be determined without drift correction, i.e., without calibration. The pressure difference P PBE -P A should correspond to the difference P PBE_korr -P A_korr of the corrected pressure during the entire treatment period. By comparing the two pressure differences (not corrected by the correction difference), the correctness of the correction function, which will be described later, can be evaluated. If the pressure differences differ from each other by more than a predetermined amount, it is recommended to recalibrate the system.

[0070] Step a)

[0071] Similar to Figure 2B this, Figure 4 it shows the signal change process of the clamped tube after the clamping device is closed. However, as an example, the force signal of the first pressure sensor PA is shown here in the form of a voltage value in volts (V) that varies with time t in seconds (s). At time t0 (t0 = 0 s), the clamping device is closed. From Figure 2B the known signal change process shows the time periods before and during treatment. The decrease in the signal change process can be explained by the viscoelasticity of the tube material, which affects the pressure transmission between the force sensor and the fluid in the tube. The elastic part of the tube generates a restoring force. The viscous part of the tube causes slow irreversible deformation of the tube. This tube deformation causes a decrease in the restoring force and, therefore, also a decrease in the force with which the tube presses on the force sensor. Figure 4The reset force change process shown is also referred to as the drift signal. In order to be able to represent the force signal or pressure signal of the force sensor as a signal that depends only on the internal tube pressure, it is useful to determine the drift signal so that the drift signal can be calculated / eliminated from the measured force signal or pressure signal, that is, the drift signal is subtracted from the measured force signal.

[0072] The viscoelastic behavior of the tube generally follows Equation (1), such that the drift signal can be described as a mathematical correction function and thus follows the following equation:

[0073] f(t) = a0·t -b (1)

[0074] Here, t is time, and a0 and b are unknown constants. The unit of f(t) is V because the force signal is output as a voltage value.

[0075] To further use the equation, it is useful to determine the constants a0 and b by fitting. For this purpose, the pumping ratio of the pump BP to the FPE or FPA must be adjusted to generate a constant internal tube pressure. In addition, a constant internal tube temperature is required. The substitute flowing through the tube is preheated to 36°, such that the internal tube temperature is also constant. In addition, the force signal of the pressure sensor, here the first pressure sensor PA, is determined in the measurement. However, the force signal of another pressure sensor such as the second pressure sensor PBE can also be used. The change process of the force signal of the first pressure sensor PA over time can be seen in Figure 5 .

[0076] In Figure 5 , the force signal is shown as a voltage in units of volts [V] as a function of time t in units of seconds [s]. In the time range from 0 s to approximately 1200 s, during the so-called "start-up" period, there is a state before the tube is effectively used (i.e., before treatment). Before treatment, no patient is connected to the dialysis machine 6, and in this case, the dialysis machine 6 is configured as described and shown in connection with Figure 3A . In the time range starting at approximately 1200 s, the voltage signal during treatment is shown, also referred to as "treatment". During treatment, the patient is connected to the dialysis machine 6, which is then configured as described and shown in connection with Figure 7 .

[0077] To be able to use this force signal to determine the constants a0 and b, the corresponding signal values of the force signal f(t = t1) and f(t = t2) are determined at two specific times t1 and t2 in the range before treatment in the fitting. In the Figure 5 shown example, the time points t1 = 600 s and t2 = 800 s are selected. This results in the following system of equations of formulas (2) and (3), which must be solved to obtain the constants a0 and b:

[0078] If (t = t1) = a0·t1 -b (2)

[0079] IIf (t = t2) = a0·t2 -b (3)

[0080] From Equation I, i.e., formula (2), a0 can be expressed as follows:

[0081] a0 = f(t = t1)·t1 b (4)

[0082] Substituting a0 in the form shown in formula (4) into formula (3) gives b in the form shown in formula (5), where b depends only on the known times t1, t2 and the corresponding signal values of the force signals f(t = t1) and f(t = t2), and can thus be calculated:

[0083] b = ln(f(t = t2)) – ln(f(t = t1)) / (ln(t1) – ln(t2)) (5)

[0084] After determining the value of b, this value can be substituted into formula (4) such that the value of the constant a0 is obtained, and Equation (1) represents the viscoelastic behavior of the tube used. Given the above chosen times t1 and t2 and the voltage value applicable to this experiment, the value of a0 is 1.19 and the value of b is 0.03.

[0085] Step a) is shown here by way of example with a PA pressure sensor and is carried out similarly to a PBE pressure sensor.

[0086] Step b)

[0087] Next, the measured force signal will be corrected and converted into a pressure signal using an appropriate pressure reference signal. For example, when the force signal drops, this is done during the pre-treatment phase and when the internal tube pressure changes, or via a second constant pressure level with a different pressure difference compared to the first level. For example, when the tube is disconnected from the substitute ports SP1, SP2 to prepare for treatment, the internal tube pressure drops. The second pressure level can be set by different pumping ratios of the blood pump and the flow pump. Step b) is carried out by way of example with a first pressure sensor PA.

[0088] First, from the force signal P measured using the first pressure sensor PA S_gem subtract the drift signal f(t) with the values calculated for a0 and b (the value of f(t) obtained from Equation (1)), and the output is a voltage value (in V). Thus, the corrected force signal P S_Korr follows the following equation (formula (6)):

[0089] P S_Korr = P S_gem – f(t) (6)

[0090] Then, the pressure reference value P PHOP is obtained using the first pressure reference sensor PHOP in mmHg and is plotted in the figure as a function of the associated voltage value P in [V] S_Korr varying, shown as an example in Figure 6 .

[0091] In the figure of Figure 6 , the pressure reference value P measured on the y-axis PHOP is plotted as points above the voltage value P calculated on the x-axis S_korr , and the linear progression / variation of these points is shown. Consistent with this, the straight line A is mathematically determined, which preferably extends through these points and thus represents the relationship between the voltage value P S_korr and the pressure correction value P calculated therefrom A_Korr . This relationship can be mathematically expressed in the form of formula (7) as follows:

[0092] P A_Korr = m·P S_korr + t (7)

[0093] Here, m is the slope of the line, also called the scaling value, and t is the pressure reference value at the intersection of the line with the y-axis and is also called the offset value. In the example shown, the scaling value is 5278 mmHg / V and the offset value is 23 mmHg.

[0094] This means that before the treatment and step b) are completed, the corrected and thus correct pressure signal P of the first clamping device, i.e., the first pressure sensor PA, is known A_korr .

[0095] The way step b) is performed on the PBE pressure sensor is similar to the procedure for the PA pressure sensor shown here, but here the PV pressure reference sensor is used instead of the PHOP pressure reference sensor as a reference.

[0096] For example, since the internal tube pressure value and / or the internal tube temperature can change from the pre-treatment state to the state during treatment, it is recommended to repeatedly perform the correction of the measured force signal of the first pressure sensor and / or the second pressure sensor during treatment.

[0097] Step c)

[0098] During treatment, Figure 2A the settings shown change as Figure 7 shown. In Figure 7In it, the arterial tube portion 1a and the venous tube portion 1b can be seen connected to the patient. In this case, the patient's heart substitutes for the dialysate inflow and outflow pumps. The (arm) artery connected to the arterial tube portion 1a and the (arm) vein of the patient connected to the venous tube portion 1b are connected to each other via an artificial connector 16, particularly via a patient shunt. Therefore, the same blood pressure and the same blood flow value exist in the patient's vein and artery (which can also be generally referred to as blood vessels). By providing a bypass on the dialyzer, the same blood pressure and the same blood flow value also exist in the arterial tube portion 1a and the venous tube portion 1b, and thus in the entire system composed of the tube and the patient's vein. For experiments, it is imaginable to simulate an experimental patient loop with a water pump, a heating water bath, and a backpressure valve.

[0099] Step c) follows the same / identical principle of calibration and reference as step b). Again, the measured force signal of the pressure sensor is corrected by the correction signal found in step a), and the corrected pressure signal can be calculated based on the relationship between the corrected pressure signal and the corrected force signal known from step b) (see formula (6), where the scaling value and the offset value are determined in step b)).

[0100] Step c) can be performed for the first PA pressure sensor and the second PBE pressure sensor. However, here a conventional PV pressure reference sensor is used as the pressure reference sensor for both the PBE pressure sensor and the PA pressure sensor to allow simultaneous reference of the PA pressure signal and the PBE pressure signal.

[0101] For simplicity, by switching the dialyzer flow to the bypass, the pressure reference sensor PV can be used to reference only the pressure signal of the second pressure sensor PBE. Due to the production-related identical characteristics of the tube at the PA clamping device position and the PBE clamping device position, the correction function found for the PBE pressure signal can be applied to the PA pressure signal, even though this method is not as accurate as separately determining the correction functions for the PA pressure signal and the PBE pressure signal.

[0102] The result of the method according to the present invention

[0103] After filtering and scaling the corrected pressure signal, this signal can be compared with the corresponding, directly measured pressure reference signal. This comparison is shown in Figure 8 with the corrected pressure signal P A_korr and the corresponding pressure reference signal P PHOP as an example.

[0104] Figure 8 The illustration in shows the variation process of the calculated pressure correction signal P A_Korr and the directly measured pressure reference signal P PHOPThe change processes are consistent. This means that the mathematical correction function from (1) together with the values calculated for a0 and b can eliminate the drift change process, but this is only effective when the internal tube pressure and internal tube temperature are constant. For example, if the internal tube pressure changes when measuring the second voltage value f(t2), the correction function is not suitable for describing the change process of the drift signal.

[0105] Referability

[0106] In the following text, Figure 9 and Figure 10A shows the comparison of the pressure change processes of the conventionally used pressure sensors for measuring the arterial pressure P A and the dialyzer inlet pressure P PBE with the pressure change processes of the corresponding pressure reference sensors PHOP and PV, respectively.

[0107] In Figure 9 , during the pre-treatment, the pressure change process of the conventionally used first pressure sensor PA_herk for measuring the arterial pressure is compared with the pressure change process of the first pressure reference sensor PHOP. The pressure change process in mmHg is shown over time t in seconds in the change process. In addition, the pressure change process of the blood pump BP is also shown, which repeatedly shows a pressure of 0. The blood pump BP is repeatedly stopped to generate constant pressure values for the PA_herk sensor and the PHOP sensor.

[0108] It can be seen that the curves of the two pressure signals of the PA_herk pressure sensor and the PHOP pressure reference sensor are similar and extend parallel to each other, where the parallel shift / pressure difference of the curves is approximately 20 mmHg. The difference between the two pressure signal curves is due to the height difference between the first pressure sensor PA_herk and the first pressure reference sensor PHOP. In this exemplary configuration, the first pressure reference sensor PHOP is installed higher than the first pressure sensor PA (see Figure 2A ).

[0109] Although the pressure difference between the conventional pressure sensor and the pressure reference sensor must be considered, Figure 9 the comparison in

[0110] Figure 10A shows that the pressure reference sensor is suitable as a reference sensor for the arterial pressure. Figure 10BA diagram depicting the time course of the blood pump flow in ml / min and the simulated patient pressure in mmHg as compared to the time course of the blood pump flow in ml / min and the simulated patient pressure in mmHg is shown. Figure 10A The pressure values ​​are recorded simultaneously.

[0111] In the range where the blood pump flow is 0, that is, when the blood pump is stopped, the pressure signals of the sensors PA_herk, PBE_herk and PV match each other and are constant. In these constant pressure ranges, the pressure change processes of the two pressure sensors PA_herk and PBE_herk are basically consistent, and there is a pressure difference with the pressure change process of the pressure reference sensor PV, which is about 20 mmHg in this case and can be interpreted as the height difference between the pressure sensors PA_herk, PBE_herk and the pressure reference sensor PV.

[0112] Likewise, although the pressure difference between the conventional pressure sensor and the pressure reference sensor needs to be considered, Figure 9 The comparison in shows that the second pressure reference sensor is suitable as a reference sensor for arterial pressure and dialysate inlet pressure during treatment.

[0113] Temperature drift

[0114] So far, the above description assumes a constant internal tube pressure and a constant internal tube temperature. However, between step b) and step c), i.e. between the phase before treatment and the phase during treatment, there may be a temperature difference in the filling tube, which may lead to a linear deviation between the reference sensor value and the pressure sensor value.

[0115] For PBE pressure sensors and PV pressure reference sensors, Figure 11A This deviation is shown by way of example in the diagram of FIG. Figure 11B The corresponding temperature course at the measuring points of the PBE pressure sensor and the PV pressure reference sensor is shown. In order to be able to determine the temperature at these two measuring points, it is necessary to integrate the temperature sensor into the PBE clamp and / or into the PA clamp. Here, the calibration before treatment (up to about 900 seconds) is carried out at T1, for example at 35.8°C, and the calibration during treatment is carried out at T2, for example at 37.2°C. Due to the temperature difference ΔT (= T2-T1) before and during treatment, which is 1.4°C here, Figure 11B The calculated PBE pressure signal shown does not follow the PV reference signal during treatment, but deviates linearly from it. Studies have shown that the deviation between the pressure signal and the reference signal is linearly proportional to the temperature deviation before and during treatment. An empirically determined correction function can be used to correct the pressure signal.

[0116] Figure 12AShows the pressure deviation between the pressure signal and the reference signal and the straight line B found for it varying over time t in seconds. In this example, the straight line equation has the following form, shown in formula (8):

[0117] PBE 信号 = -0.0064182·ΔT + 3.4282 (8)

[0118] Figure 12B Shows the PBE pressure signal corrected using the determined formula (8), now again shown to be consistent with the PV reference signal.

[0119] As an alternative to the linear relationship between the deviation between the pressure signal and the reference signal and the temperature deviation before and during treatment, a polynomial relationship may also exist. However, calculating the corresponding formula requires more computing power, although this relationship can represent the deviation more accurately than the linear relationship.

[0120] Same as Figure 12A and Figure 13A Shows the pressure deviation between the pressure signal and the reference signal and the polynomial C calculated for it over time t in seconds. In this example, the PBE pressure signal follows the polynomial deviation shown in formula (9):

[0121] PBE 信号 = 2.6287·10 -6 ·ΔT 2 - 0.018486 + 15.8826 (9)

[0122] Figure 13A Shows the PBE pressure signal corrected using the determined formula (9), now again shown to be consistent with the PV reference signal.

[0123] Second embodiment

[0124] The second embodiment is similar to the first embodiment, so only the differences from the first embodiment are described below.

[0125] The reference pressure measurements of the pressure signals PBE and PA during step c) (during treatment) can also be performed using the venous clamp SAKV and the arterial clamp SAKA as an alternative to the method described in the first embodiment.

[0126] To this end, in an exemplary first configuration, the dialyzer flow is switched to bypass and the line clamps SAKV and SAKA are closed. A pressure-tight connection is formed in the line. The blood pump BP is stopped. However, due to the delay, the blood pump BP continues to rotate for a short time after stopping, such that a negative pressure is formed in the arterial line section and a positive pressure is formed in the venous line section, and over time, both have the same pressure ratio relative to each other. The PBE pressure signal is calibrated using the PV pressure reference sensor. The PA pressure signal can also be calibrated using the PV pressure reference sensor.

[0127] Since the closed line clamps SAKV and SAKA disconnect the patient from the extracorporeal circuit, this alternative version can be performed in step c) independently of the patient. However, in this case, the blood no longer circulates in the extracorporeal circuit, so the blood may coagulate in the circuit and the temperature may drop. However, the coagulation of the blood and its temperature drop depend on the duration of the blood pump stop, so the duration shown should be as short as possible.

Claims

1. A calibration method for calibrating a first pressure sensor or force sensor (PA), wherein the first pressure sensor or force sensor (PA) measures a first pressure of a liquid present in a tube (1) in the form of a force signal, the tube (1) being a dialyzer tube in an extracorporeal circuit, and wherein the first pressure or force sensor (PA) is directly adjacent to the tube (1) and integrated or inserted into a first clamping device. It is characterized by the following steps: a) Performing regression analysis and prediction on a correction function independent of at least one tube parameter to find a correction signal for correcting a drift signal achieved by clamping the tube within the first clamping device using a corresponding stress or pressure reference signal measured by a first force or pressure reference sensor (PHOP) at a constant internal tube pressure and at a constant internal tube temperature; b) Before effectively using the tube, performing a first calibration on a pressure or force signal measured by the first pressure or force sensor (PA) and corrected using the correction signal, with the force or pressure reference signal measured by the first force or pressure reference sensor (PHOP), where the tube is connected to a patient during the effective use of the tube; And c) During the effective use of the tube, performing a second calibration on the pressure or force signal measured by the first pressure or force sensor (PA) and corrected using the correction function, with the force or pressure reference signal measured by a second force or pressure reference sensor (PV).

2. The calibration method according to claim 1, wherein In addition to the first pressure, a second pressure or force signal is measured using a second force sensor or pressure sensor (PBE) integrated in the second clamping device, and the second pressure or force signal is subsequently corrected; And The second pressure or force signal of the second pressure or force sensor (PBE) is calibrated using the force or pressure reference signal measured by the second force or pressure reference sensor (PV) during the first calibration and the second calibration.

3. The calibration method according to claim 1, characterized in that, The tube (1) includes an arterial portion (1a) and a venous portion (1b) and the first pressure sensor or force sensor and / or the second pressure sensor or force sensor (PA, PBE), and in the case before effectively using the tube (1), the first force or pressure reference sensor (PHOP) is arranged at the arterial portion (1a), while the second force or pressure reference sensor (PV) is arranged at the venous portion (1b), and the second force or pressure reference sensor (PV) is an ordinary pressure sensor not integrated into a clamping device and not generating a drift signal.

4. The calibration method according to claim 2, wherein, The first force or pressure reference sensor and the second force or pressure reference sensor (PHOP, PV) each have a higher measurement accuracy compared to the first pressure or force sensor and the second pressure or force sensor (PA, PBE) respectively.

5. The calibration method according to claim 2, wherein To calibrate the first force or pressure sensor and the second force or pressure sensor (PA, PBE), the internal tube pressure in the arterial portion (1a) of the tube (1) is matched to the internal tube pressure in the venous portion (1b) of the tube (1) via a bypass circuit.

6. The calibration method according to claim 1, wherein The constant internal tube pressure is obtained by adjusting the pumping ratio between a first pump and a second pump before effectively using the tube.

7. The calibration method according to claim 1, wherein The drift signal is or corresponds to the restoring force of the clamped tube (1).

8. The calibration method according to claim 2, wherein The first pressure or force signal and / or the second pressure or force signal is converted into a pressure signal via linear recursion by means of the force or pressure reference signal of the first pressure reference sensor and / or the second pressure reference sensor.

9. The calibration method according to claim 4, wherein The first pressure or force sensor (PA) is arranged at the inlet opening of the first pump, and the second pressure or force sensor (PBE) is arranged at the outlet opening of the first pump.

10. A device, comprising: An extracorporeal circuit; at least one pressure or force sensor (PA, PBE) integrated in a clamping device for measuring the internal tube pressure in a fluid-filled tube (1) having an arterial part (1a) and a venous part (1b). At least one force or pressure reference sensor (PHOP, PV) provided for referencing the pressure or force signal output by the pressure sensor or force sensor (PA, PBE), not designed as a clamping device and including at least a first pump and a second pump, and the at least one force or pressure reference sensor is provided to apply the following calibration method: Calibrating the pressure or force signal of the at least one pressure or force sensor (PA, PBE) by means of the reference signal of the at least one force or pressure reference sensor (PHOP, PV) according to claim 1.

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