Calibration element, control for a calibration element, calibration system, conveyor system, and method for operating a calibration element

Abstract

The invention relates to a calibration element (100) comprising: at least one measuring chamber (120, 121, 122); a first liquid sensor (130), that is arranged at a first measuring point at an inflow to the measuring chamber (120, 121, 122), for detecting the presence of a liquid; and a second liquid sensor (131, 132) that is arranged at a second measuring point at an outflow of the measuring chamber.

Description

[0001] Calibration element, control for a calibration element, calibration system, conveyor system and method for operating a calibration element

[0002] The invention relates to a calibration element, a control for a calibration element, a calibration system, a conveyor system and a method for operating a calibration element.

[0003] In industrial processes, such as bioprocessing, pumps are used to feed media to a reaction (e.g., in a bioreactor). It is essential, among other things, to know exactly how much medium is being pumped by the pump, for example, in fed-batch or perfusion processes. The necessary calibration of the pumps in relation to their flow rate is now usually performed using a load cell. If the pump is equipped with a pump tube or other replaceable elements, this calibration also depends on these elements—in particular, the material, changes in elasticity, and "squeezing behavior" of the elements over time. Therefore, it must be repeated whenever this element, such as the pump tube, is replaced.

[0004] The solutions used to date in bioprocess technology always require a complex process involving a load cell or calibration of the pumping process. A considerable amount of time and medium are required prior to the test to perform the weight-related calibration using a load cell. Especially in highly parallel systems, the initial time required by the user is very high. Furthermore, the currently used calibration procedure using a load cell limits or hinders the use of disposable tubing kits. This is due to the fact that disposable tubing kits are inserted directly by the user, or the connection to scales / weighing bottles is impractical (time and material expenditure).

[0005] In addition, there is a risk of contamination of the culture due to additional hose connections, which users would like to avoid as much as possible in bioprocesses.

[0006] Common flow sensors (especially thermal mass flow sensors) cannot normally be used for pump calibration, as this requires precise knowledge of media parameters, such as thermal capacity. Furthermore, commercially available flow sensors are not suitable for the low dosing rates required for small bioreactor systems.

[0007] It is therefore an object of the invention to provide a calibration option that can be carried out safely with reduced material and time expenditure and can be used in particular even with low dosing rates and with disposable tube kits.

[0008] This object is achieved according to a first aspect of the invention by a calibration element comprising at least one measuring chamber and a first liquid sensor arranged at a first measuring point at an inlet to the measuring chamber for detecting a presence of a liquid and a second liquid sensor arranged at a second measuring point at an outlet of the measuring chamber.

[0009] The invention includes the realization that calibration can be carried out via precise volumetric measurement instead of weighing. The invention thus makes a load cell superfluous and, by using the measuring chamber, allows calibration to be carried out during priming, i.e. during the initial filling of the hoses, of the system. By measuring the time required to fill one or more precisely specified volumes, i.e. the at least one measuring chamber, the volume flow can be determined using the equation Q=V / t. This means that a volume flow can be determined directly in the setup for each pump setting and can be used for calibration. This can be used both initially and continuously at any time to determine a current volume flow, for example after changing accessories or over time in order to detect deviations in pump behavior.To determine the volume flow, the medium flows through one or more measuring chambers with a precisely known volume. Sensors are located at the inlets and outlets to detect the presence of the fluid. When the fluid enters and exits one of the chambers, a time stamp can be recorded and stored, allowing the volume flow to be determined according to Q=V / t.

[0010] The invention thus allows for easy handling, as calibration can be performed virtually "in passant" during line priming, saving both time and medium. The described setup can also be used to calibrate an integrated flow sensor to a required resolution range and the fluid properties of the application, which particularly allows use in the range of low dosing rates. A further aspect of the invention is that the possible storage of the recorded volume flows allows a comparison of current and historical flow parameters, thus enabling automated verification. In addition, the invention allows the detection of bubbles in the system by comparing volume flows.

[0011] Embodiments of the calibration element according to the invention are described below.

[0012] In one embodiment, the inlet and outlet areas of the at least one measuring chamber are designed so that fluctuations, for example, in surface tension, can be compensated. For this purpose, it is advantageous if the at least one measuring chamber has a diamond-shaped cross-section and flows from one vertex of the diamond to the opposite vertex. Embodiments in which the at least one measuring chamber has the shape of a rhombohedron or a double pyramid are particularly preferred.

[0013] In one embodiment of the calibration element, the first and / or second liquid sensor is configured to detect the presence of liquid optically, acoustically, or via a resistance or impedance measurement. Contacting the first and / or second liquid sensor can preferably be made via cables or contacts, such as spring contacts.

[0014] In a preferred embodiment, a calibration element further comprises a flow sensor, in particular a mass flow sensor, fluidically connected to the at least one measuring chamber. By integrating a flow sensor, the flow can be verified during the process, including a possible recalibration of the flow sensor. By initially calibrating the flow sensor with respect to the medium used (for example, with respect to thermal capacity), deviations in the pumping behavior, in particular, can be continuously detected during the process. This sensor can therefore also be used later in the process for precise tracking of the pumping behavior. Its flow integral represents the total volume delivered.This is particularly useful when using pump hoses whose behavior changes during the process (e.g., due to running-in behavior or aging of the hose material). Such a deviation can then be detected and compensated for by a flow sensor calibrated using the initial volume flow determination. The flow sensor is preferably located between the pump and the at least one measuring chamber. Alternatively, it can also be positioned fluidically downstream of the measuring chamber.

[0015] In a further embodiment, the calibration element comprises at least two measuring chambers, each with a first and a second liquid sensor. The measuring chambers can be connected in parallel or in series.

[0016] By connecting multiple measuring chambers in series or in parallel, additional accuracy can be achieved by averaging the results from the multiple measuring chambers. Furthermore, gross irregularities in material transport or volume flow can be detected, especially in measuring chambers that are filled one after the other. Likewise, the filling time of the different measuring chambers can be determined at different pumping rates, thus achieving a multi-point calibration of the pump by using a different pumping rate for each filling of a subsequent measuring chamber. A series connection is particularly advantageous for this purpose.

[0017] Preferably, the second liquid sensor of a first measuring chamber is simultaneously the first liquid sensor of a second measuring chamber arranged directly downstream of the first measuring chamber.

[0018] According to a second aspect, the invention relates to a controller for a calibration element having at least one measuring chamber. The controller is designed to receive a first signal from a first liquid sensor arranged at a first measuring point on an inlet to the measuring chamber and a second signal from a second liquid sensor arranged at a second measuring point on an outlet of the measuring chamber, which second signal indicates the presence of liquid at the respective measuring point. Upon receipt of the first and second signals, the controller assigns a time stamp and determines a volume flow value of the measuring chamber from the comparison of the two time stamps and a previously known volume between the first measuring point and the second measuring point.

[0019] In one embodiment of the controller for a calibration element with a first and a second measuring chamber, the controller is configured to calculate an average value from the volume flow value of a first measuring chamber and the volume flow value of a second measuring chamber. If more than two measuring chambers are present, the controller can also be configured to calculate an average value from the volume flow values ​​of all or several measuring chambers.

[0020] Alternatively or additionally, the controller can be designed to initialise a first pump rate of a pump connected to the calibration element for filling a first measuring chamber and to determine a first volume flow value for the first pump rate, and to initialise a second pump rate of the pump connected to the calibration element for filling a second measuring chamber and to determine a second volume flow value for the second pump rate. If more than two measuring chambers are present, the controller can also be designed to initialise a respective pump rate of the pump connected to the calibration element for each measuring chamber and to determine a respective volume flow value for the respective pump rate. Several measuring chambers can then be filled with the same pump rate, and an average value can be calculated for each pump rate.

[0021] In a further embodiment, the controller, in the case of a calibration element with a flow sensor, is configured to receive a flow signal from the flow sensor and to calibrate the flow sensor according to at least one previously determined volume flow. The controller can be further configured to track the pumping behavior of a pump connected to the calibration element after calibrating the flow sensor.

[0022] According to a third aspect, the invention relates to a calibration system comprising a calibration element according to the first aspect of the invention and a controller according to a second aspect of the invention.

[0023] In one embodiment, the at least one measuring chamber can be designed as a single-use component and then removed from the system after an initial calibration. According to a fourth aspect, the invention relates to a conveying system comprising a calibration system according to the third aspect of the invention and a pump, in particular a roller pump or peristaltic pump, fluidically connected to the calibration element via an inlet hose.

[0024] According to a fifth aspect, the invention relates to a method for operating a calibration element with at least one measuring chamber and a first liquid sensor arranged at an inlet to the measuring chamber and a second liquid sensor arranged at an outlet of the measuring chamber, comprising the steps:

[0025] - Detecting the presence of liquid at a first measuring point at the inflow to the measuring chamber and outputting a first signal

[0026] - Receiving the first signal and assigning a first timestamp

[0027] - Detecting the presence of liquid at a second measuring point at the outlet of the measuring chamber and outputting a second signal

[0028] - Receiving the second signal and assigning a second timestamp

[0029] - Compare the first and second timestamp

[0030] - Determining a volume flow value from the comparison of the first and second timestamp and a previously known volume between the first and second measuring point.

[0031] In one embodiment, the method comprises the step of forming an average value from the volume flow value of a first measuring chamber and the volume flow value of a second measuring chamber.

[0032] In a further embodiment, the method further comprises the steps:

[0033] - prior to detecting the presence of liquid at the first measuring point at the inlet to a first measuring chamber, initializing a first pumping rate of a pump connected to the calibration element for filling the first measuring chamber; - determining a first volume flow value for the first pumping rate;

[0034] - before detecting the presence of liquid at the first measuring point at the inflow to a second measuring chamber, initialising a second pumping rate of a pump connected to the calibration element for filling the second measuring chamber;

[0035] - Determining a second flow rate value for the second pumping rate.

[0036] The method may further comprise the following steps:

[0037] - Receiving a flow signal from a flow sensor fluidically connected to the at least one measuring chamber

[0038] - Calibrating the flow sensor according to at least one previously determined volume flow.

[0039] Additionally, this method may include tracking a pumping behavior of a pump connected to the calibration element.

[0040] Possible designs and advantages described with reference to the calibration element also apply to the calibration system, the control system, the conveyor system, and the method. Thus, any embodiments and further developments of the calibration element, as previously explained, can also be used for the calibration system, the control system, the conveyor system, and the method. For further advantages, design variants, and details of these additional aspects and their possible further developments, please refer to the previous description of the corresponding features and further developments of the calibration element.

[0041] Preferred embodiments of the invention are explained by way of example with reference to the accompanying figures. They show:

[0042] Fig. 1 shows an embodiment of a conveyor system according to the third aspect of the invention;

[0043] Fig. 2 shows an embodiment of a method for operating a calibration element according to the fifth aspect of the invention. Fig. 1 shows an embodiment of a conveying system 1000 according to the third aspect of the invention. In addition to a reservoir 220 and a bioreactor 300, the conveying system 1000 comprises a calibration system 500 with a calibration element 100 and a controller 400. The calibration element 100 is fluidically connected to a pump 200 via an inflow hose 210. Another inflow hose 310 connects the calibration element 100 to the bioreactor 300. In the conveying system 1000, liquids are transported from the reservoir 220 into the bioreactor 300. The addition of liquid is controlled thanks to the calibration element 100.

[0044] In the embodiment shown, the calibration element 100 comprises three measuring chambers 120, 121, 122 as well as a first liquid sensor 130 arranged at a first measuring point on an inlet to the measuring chamber 120 for detecting the presence of a liquid and a second liquid sensor 131 arranged at a second measuring point on an outlet of the measuring chamber 120. The second liquid sensor 131 of the first measuring chamber 120 is simultaneously the first liquid sensor of the second measuring chamber 121 arranged directly downstream of the first measuring chamber. The second liquid sensor 132 of the second measuring chamber 121 is simultaneously the first liquid sensor of the third measuring chamber 122 arranged directly downstream of the second measuring chamber 121. Furthermore, the third measuring chamber also has a second liquid sensor 133 arranged at the outlet of the third measuring chamber. In the embodiment shown, the measuring chambers are connected in series.In the exemplary state shown, the first measuring chamber 120 is already completely filled with the liquid from the reservoir 220, and the second measuring chamber is currently being filled. Using multiple measuring chambers offers the advantage of allowing the volume flows determined in each of the measuring chambers to be averaged, which allows for greater accuracy, or that different pumping rates can be used for the different measuring chambers, thus allowing volume flows to be determined for different pumping rates.

[0045] The measuring chambers 120, 121, and 122 each have a diamond-shaped cross-section and are flowed through from one tip of the diamond to the opposite tip. This design allows for particularly good compensation of fluctuations, for example, in surface tension. In the illustrated embodiment, the liquid sensors 130, 131, 132, and 133 are designed to optically detect the presence of liquid. Alternatively, acoustic detection or detection via a resistance or impedance measurement are also possible. The calibration element 100 shown further comprises a flow sensor 110, which is fluidically connected to the measuring chambers and is a mass flow sensor in this case.

[0046] The controller 400 for the calibration element 100 is designed to receive a first signal from the first liquid sensor 130 arranged at the first measuring point at the inflow to the first measuring chamber 120 and a second signal from the second liquid sensor 131 arranged at the second measuring point at the outflow of the first measuring chamber 120, which indicates the presence of liquid at the respective measuring point, and to assign a time stamp upon receipt of the first and second signals and to determine a volume flow value of the first measuring chamber from the comparison of the two time stamps and a previously known volume between the first measuring point and the second measuring point.

[0047] 120. The controller 400 is also designed to receive a first signal from the first liquid sensor 131 arranged at the first measuring point at the inflow to the second measuring chamber 121 and a second signal from the second liquid sensor 132 arranged at the second measuring point at the outflow of the second measuring chamber 121, which indicates the presence of liquid at the respective measuring point, and to assign a time stamp upon receipt of the first and second signals, and to determine a volume flow value of the second measuring chamber from the comparison of the two time stamps and a previously known volume between the first measuring point and the second measuring point.

[0048] 121. The controller 400 is also designed to receive a first signal from the first liquid sensor 132 arranged at the first measuring point at the inflow to the third measuring chamber 122 and a second signal from the second liquid sensor 133 arranged at the second measuring point at the outflow of the third measuring chamber 122, which indicates the presence of liquid at the respective measuring point, and to assign a time stamp upon receipt of the first and second signals and to determine a volume flow value of the third measuring chamber from the comparison of the two time stamps and a previously known volume between the first measuring point and the second measuring point.

[0049] 122 to be determined.

[0050] Furthermore, the controller is designed to calculate an average value from the volume flow value of the first measuring chamber 120 and the volume flow value of the second measuring chamber 121 and the volume flow value of the third measuring chamber 122. For a further application, the controller is also designed to initialize a first pump rate of the pump 200 connected to the calibration element for filling the first measuring chamber 120 and to determine a first volume flow value for the first pump rate, and to initialize a second pump rate of the pump 200 connected to the calibration element for filling the second measuring chamber 121 and to determine a second volume flow value for the second pump rate, and to initialize a second pump rate of the pump 200 connected to the calibration element for filling the third measuring chamber 122 and to determine a third volume flow value for the third pump rate.

[0051] Furthermore, the controller 400 shown is configured to receive a flow signal from the flow sensor 110 and to calibrate the flow sensor 110 according to at least one of the previously determined volume flows. Furthermore, the controller is configured to track a pumping behavior of the pump 200 connected to the calibration element after calibrating the flow sensor.

[0052] Fig. 2 shows an embodiment of a method for operating a calibration element according to the fifth aspect of the invention. The calibration element has at least one measuring chamber, a first liquid sensor arranged at an inlet to the measuring chamber, and a second liquid sensor arranged at an outlet of the measuring chamber. In a first step S1, the method comprises detecting the presence of liquid at a first measuring point at the inlet to the measuring chamber and outputting a first signal. Then, in step S2, the first signal is received, and a first timestamp is assigned.

[0053] In step S3, the presence of liquid is detected at a second measuring point at the outlet of the measuring chamber, and a second signal is output. In the subsequent step S4, the second signal is received, and a second timestamp is assigned.

[0054] In step S5, the first and second timestamps are compared.

[0055] From the comparison of the first and second time stamps and a previously known volume between the first and second measuring points, a volume flow value is then determined in step S6.

[0056] In an embodiment not shown here, if two measuring chambers are present in the calibration element, the method can comprise the step of calculating an average value from the volume flow value of the first measuring chamber and the volume flow value of the second measuring chamber. In a further embodiment not shown, the method further comprises the steps: - before detecting the presence of liquid at the first measuring point at the inlet to a first measuring chamber, initializing a first pump rate of a pump connected to the calibration element for filling the first measuring chamber;

[0057] - Determining a first volume flow value for the first pumping rate; - Before detecting the presence of liquid at the first measuring point at the inflow to a second measuring chamber, initializing a second pumping rate of a pump connected to the calibration element for filling the second measuring chamber;

[0058] - Determining a second flow rate value for the second pumping rate.

[0059] If a flow sensor is included in the calibration element, the method can further comprise the following steps: receiving a flow signal from a flow sensor fluidically connected to the at least one measuring chamber and calibrating the flow sensor according to at least one previously determined volume flow.

[0060] List of reference symbols

[0061] 100 calibration elements

[0062] 110 Flow sensor

[0063] 120 measuring chamber

[0064] 121 Measuring chamber

[0065] 122 measuring chamber

[0066] 130 liquid sensor

[0067] 131 Liquid sensor

[0068] 132 Liquid sensor

[0069] 133 Liquid sensor

[0070] 200 pump

[0071] 210 Inlet hose

[0072] 220 Reservoir

[0073] 300 bioreactor

[0074] 310 inlet hose

[0075] 400 Control

[0076] 500 calibration system

[0077] 1000 conveyor system

Claims

Claims 1. Calibration element (100) comprising at least one measuring chamber (120, 121, 122) and a first liquid sensor (130) arranged at a first measuring point at an inlet to the measuring chamber (120, 121, 122) for detecting a presence of a liquid and a second liquid sensor (131, 132) arranged at a second measuring point at an outlet of the measuring chamber.

2. Calibration element (100) according to claim 1, wherein the at least one measuring chamber has a diamond-shaped cross-section and is flowed through from one tip of the diamond to the opposite tip, wherein in particular the at least one measuring chamber has the shape of a rhombohedron or a double pyramid.

3. Calibration element (100) according to one of the preceding claims, wherein the first and / or the second liquid sensor is designed to detect a presence of liquid optically, acoustically or via a resistance or impedance measurement.

4. Calibration element (100) according to one of the preceding claims, further comprising a flow sensor (110) fluidically connected to the at least one measuring chamber, in particular a mass flow sensor.

5. Calibration element (100) according to one of the preceding claims with at least two measuring chambers (120, 121, 122) each having a first and a second liquid sensor, wherein the at least two measuring chambers are fluidically connected in series and wherein in particular the second liquid sensor of a first measuring chamber is simultaneously the first liquid sensor of a second measuring chamber arranged directly downstream of the first measuring chamber.

6. Calibration element (100) according to one of claims 1 to 4 with at least two measuring chambers (120, 121, 122) each with a first and a second liquid sensor, wherein the at least two measuring chambers are fluidically connected in parallel.

7. Control system (400) for a calibration element (100) with at least one measuring chamber, wherein the control system is designed to receive a first signal from a first liquid sensor (130) arranged at a first measuring point at an inlet to the measuring chamber (120) and to receive a second signal from a second liquid sensor (131) arranged at a second measuring point on an outflow of the measuring chamber, which second liquid sensor indicates the presence of liquid at the respective measuring point, and to assign a time stamp upon receipt of the first and second signals and to determine a volume flow value of the measuring chamber from the comparison of the two time stamps and a previously known volume between the first measuring point and the second measuring point.

8. Controller (400) according to claim 7 for a calibration element with a first and a second measuring chamber, wherein the controller is designed to form an average value from the volume flow value of a first measuring chamber (120) and the volume flow value of a second measuring chamber (121) and / or wherein the controller is designed to initialize a first pumping rate of a pump (200) connected to the calibration element for filling a first measuring chamber and to determine a first volume flow value for the first pumping rate and to initialize a second pumping rate of the pump connected to the calibration element for filling a second measuring chamber and to determine a second volume flow value for the second pumping rate.

9. Controller (400) according to one of claims 7 or 8, which, in the case of a calibration element with a flow sensor, is designed to receive a flow signal from the flow sensor and to calibrate the flow sensor according to at least one previously determined volume flow, wherein the controller is in particular further designed to track a pumping behavior of a pump connected to the calibration element after the flow sensor has been calibrated.

10. Calibration system (500) comprising a calibration element (100) according to one of claims 1 to 5 and a controller (400) according to one of claims 7 to 9.

11. Conveying system (1000) comprising a calibration system according to claim 10 and a pump (200) fluidically connected to the calibration element via an inlet hose (210), in particular a roller pump or a peristaltic pump.

12. A method for operating a calibration element (100) with at least one measuring chamber (120) and a first liquid sensor (130) arranged at an inlet to the measuring chamber (120) and a second liquid sensor (131) arranged at an outlet of the measuring chamber, comprising the steps: - detecting the presence of liquid at a first measuring point at the inflow to the measuring chamber (120) and outputting a first signal - Receiving the first signal and assigning a first timestamp - detecting the presence of liquid at a second measuring point at the outlet of the measuring chamber (120) and outputting a second signal - Receiving the second signal and assigning a second timestamp - Compare the first and second timestamp - Determining a volume flow value from the comparison of the first and second timestamp and a previously known volume between the first and second measuring point.

13. The method according to claim 12 further comprising the step of forming an average value from the volume flow value of a first measuring chamber and the volume flow value of a second measuring chamber.

14. Method according to one of claims 12 or 13 further comprising the steps: - before detecting the presence of liquid at the first measuring point at the inflow to a first measuring chamber, initialising a first pumping rate of a pump connected to the calibration element for filling the first measuring chamber; - Determining a first volume flow value for the first pumping rate; - before detecting the presence of liquid at the first measuring point at the inflow to a second measuring chamber, initialising a second pumping rate of a pump connected to the calibration element for filling the second measuring chamber; - Determining a second flow rate value for the second pumping rate.

15. Method according to one of claims 12 to 14 comprising the steps - Receiving a flow signal from a flow sensor fluidically connected to the at least one measuring chamber - Calibration of the flow sensor according to at least one previously determined volume flow and - optional tracking of the pumping behavior of a pump connected to the calibration element.

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