Procedure for verifying pipettes

Abstract

A procedure for verifying a pipette, wherein the result of verification is a release or warning message, the procedure comprising the following steps: providing a liquid measuring container for receiving the liquid volume of the pipette to be verified; a weighing sensor connected to the liquid measuring container in a force-transmitting manner, the weighing sensor outputting a measurement signal corresponding to the gravity acting on the weighing sensor; and a processing unit for detecting and processing the measurement signal of the weighing sensor; determining a first gravity at a time point from the stable measurement signal, and determining a second gravity at a time point; calculating the liquid volume of the pipette; assigning the calculated liquid volume of the pipette to one of at least one pipette volume class having a defined nominal value; having the processing unit test whether the absolute value of the volume difference is within the tolerance value of the nominal value of the assigned pipette volume class; and having the processing unit output the test result.

Description

Technical Field

[0001] The present invention relates to a procedure for verifying pipettes and an apparatus for verifying pipettes. Background Technology

[0002] It is well known that temperature, air pressure, and humidity affect the balance itself. Therefore, to compensate for changes in the weighing value caused by alterations in environmental parameters, correction factors are stored in the device, for example, in the form of curves or tables. Thus, in the environment of the weighing sensor, for example in a laboratory, temperature and humidity sensors are arranged, through which the balance is automatically calibrated according to changing environmental conditions.

[0003] Evaporation of water during the measurement process is a frequently mentioned issue. To illustrate the severity of this effect, consider the following example: at 20°C, the approximate evaporation rate of a container with an opening of 40 mm in diameter is about 20 μg / s.

[0004] In EP 1 975 577 A1, a balance for gravimetric analysis calibration of pipettes is known, which has a windproof cover and built-in temperature, air pressure and air humidity sensors.

[0005] EP 3 066 430 B1 discloses a procedure for calibrating a pipette using a balance, wherein, during the calibration process, the evaporation rate is determined, and the measurement is corrected using the determined evaporation rate. Here, the evaporation rate is corrected using data recorded during the calibration process by a climate module including an air pressure sensor, an air humidity sensor, and an air temperature sensor. Thus, since the calibration process is not based on a predefined, assumed evaporation rate, but rather on actual values ​​that depend on current climatic conditions during the calibration process, the accuracy of the measurement or the accuracy of the calibration process can be improved.

[0006] The procedure used to verify pipettes should be considered proof of pipette performance, compared to the procedure used to calibrate them. It determines whether the volume to be tested is within a predetermined range and tolerance based on weight measurements. Therefore, the result can be considered a state, not a nominal value. Calibration is a time-consuming and expensive process that requires precise documentation. During the interval between two calibrations, the user is uncertain whether the pipette volume will still conform to the calibration standards. Failure to conform to the calibration standards may cast doubt on the entire series of measurements or have a serious impact on the user's business.

[0007] The purpose of pipette verification (pipettes performance verification) is to provide immediate feedback—including written confirmation—to the user or handler that the pipette remains sufficiently accurate and usable. Conveniently, this means that the feedback provides a statement regarding whether the actual pipetting process accuracy is within defined tolerance limits, depending on the pipetting instrument's error and potential influences from the user, the fluid, and the environment. Summary of the Invention

[0008] Therefore, the purpose of this invention is to provide users with a simplified and fast procedure that requires minimal human intervention and has reliable performance.

[0009] This objective is achieved by a procedure having the features specified in this application. Advantageous embodiments of the invention are specified in other respects.

[0010] This objective is achieved through a procedure for verifying pipettes, in which the verification result is a release or warning message. The procedure includes the following steps: providing a liquid measuring container for receiving the liquid volume of the pipette to be verified; a weighing sensor connected to the liquid measuring container in a force-transmitting manner—the weighing sensor outputs a measurement signal corresponding to the gravity acting on the weighing sensor; and a processing unit for detecting and processing the measurement signal from the weighing sensor; the processing unit determining a first gravity from the stable measurement signal at the most recent stable measurement point at time point t1, wherein the most recent stable measurement point is chronologically prior to receiving the liquid volume of the pipette to be verified; the processing unit determining a second gravity from the stable measurement signal at a new stable measurement point at time point t2, wherein the new stable measurement point is chronologically prior to receiving the liquid volume of the pipette to be verified; and the processing unit calculating the liquid volume of the pipette according to the following formula: V P =ρ -1 ×(G t2 -G t1 The calculated pipette volume is allocated to at least one pipette volume class with a defined nominal class value, wherein the allocation by the processing unit minimizes the absolute value of the volume difference between the pipette volume and the nominal class value; the processing unit tests whether the absolute value of the volume difference is within the tolerance value of the nominal class value of the allocated pipette volume class; when the volume difference is within the tolerance value, the processing unit outputs a release as the test result, or outputs a warning message when the volume difference is outside the tolerance value.

[0011] The procedure is advantageous to the user because calibration intervals do not need to be defined by empirically determined data, but can be specifically tailored to the user's requirements. Therefore, the necessary calibration of pipettes can be identified when necessary, based on the impact of pipetting on the user's business and pipetting process tolerances. For the user, this may result in extended calibration intervals and cost savings due to (appropriate) postponement of calibration. In the case of shortened calibration intervals, this leads to improved quality of the pipetting process, thereby reducing or preventing material loss, non-compliant results, time loss, rework, product recalls, or reputational damage, depending on the user's business. However, calibration intervals can also remain constant, thereby allowing for timely detection of defective pipettes to trigger earlier calibration. Undetected defective pipettes can cast doubt on an entire series of measurements, as malfunctions, such as when a pipette fails to function properly due to dripping, are often subtle.

[0012] The test performed by the processing unit (130) can be based on the volume of liquid in the pipette to be verified (V). P The volume of liquid in the pipette to be measured is received a predetermined number of times. This means that in each case, after a signal is given to the operator, the volume of liquid in the pipette to be measured is received multiple times sequentially (V). P The test was conducted based on multiple existing calculations of the liquid volume in the pipette. In essence, statistical multiple measurements were performed.

[0013] When introducing the volume of liquid to be verified from the pipette, care should be taken to ensure that it is introduced into the liquid measuring container all at once or at least drop by drop, so that the processing unit will only indicate a stable measurement signal from the weighing sensor after the pipette has been completely emptied.

[0014] The signal is considered a stable measurement signal, existing within a signal band with a defined time length and signal level. This means that, starting from this point in time when the measured signal value is measured, all measured signal values ​​over a previous time period can deviate by a maximum of a defined difference.

[0015] Advantageously, the procedure is fully automated, wherein receiving the liquid volume of the pipette to be verified into the liquid measuring container triggers the verification performed by the processing unit, and wherein, after outputting the test result, the processing unit prepares to receive and verify the next liquid volume of the pipette to be verified. The procedure can display the test result without additional user interaction, and after displaying the result, it switches to prepare for additional verification.

[0016] Furthermore, the procedure may also include the following steps: determining the evaporation rate of the liquid in the liquid measuring container by processing the measurement signal over a previous time period that terminates no later than time point t1; calculating the evaporation volume between time point t1 and time point t2; and calculating the liquid volume in the pipette according to the following formula:

[0017] V P =ρ -1 ×(G t2 -G t1 +c V ×(t2-t1)). Advantageously, this time period is at least and includes ten seconds, and / or at most and includes ten times the time difference between time point t1 and time point t2. It is also advantageous to check the validity of the evaporation rate against a reference value.

[0018] In a further development of the program, when the gravity difference is less than a predetermined value, the program ends without outputting a result; or when the gravity acting on the weighing sensor is greater than a predetermined value, or when the measurement signal does not reach a stable state within a limited time period, the program ends and outputs a warning message.

[0019] The development of the procedure is characterized in that the test results are output in the form of visual, auditory, and / or electrical signals. Advantageously, for each pipette volume level, the test results are output as visual signals by means of multi-color LEDs. Furthermore, after a defined output period for the test results and visual signals, all LEDs can simultaneously flash to signal that the verification has ended and to prepare for another or new verification.

[0020] Further development of the procedure includes the following steps: providing an identification sensor for identifying pipettes and a database system for storing verification test results; detecting identification features of the pipettes, which can uniquely and accurately identify the pipettes; and storing the verification test results of the pipettes in the database system.

[0021] The procedure of the present invention described above can be executed by an apparatus comprising: a liquid measuring container for receiving a pipette volume to be verified; a weighing sensor connected to the liquid measuring container in a force-transmitting manner, the weighing sensor outputting a measurement signal corresponding to the gravity acting on the weighing sensor; and a processing unit for detecting and processing the measurement signal of the weighing sensor to execute the procedure. Advantageously, the minimum opening cross-section of the provided liquid measuring container is and includes 100 mm. 2 . Attached Figure Description

[0022] Based on the description of the embodiments shown in the accompanying drawings, details of the force measuring device according to the invention, the force measuring module according to the invention, and the program according to the invention are given. It is shown that:

[0023] Figure 1 This is a schematic structure of one embodiment of the device of the present invention;

[0024] Figure 2 It is the process of receiving the measurement signal when the volume of liquid in the pipette to be verified is received;

[0025] Figure 3 A stable measurement signal is determined by the processing unit; and

[0026] Figure 4 This is a diagram showing the calibration and verification intervals for pipettes. Detailed Implementation

[0027] Features with the same functionality and similar configuration are provided with the same reference numerals in the following description.

[0028] Figure 1 An apparatus 100 for verifying pipettes is schematically shown. The apparatus 100 shown here includes a liquid measuring container 110, a weighing sensor 120, and a processing unit 130. The liquid measuring container 110 has an opening 111 through which the liquid volume V of the pipette to be verified is measured. P It can be introduced via pipette P. It is crucial to ensure that the volume of liquid in the pipette to be verified is V. P The liquid is introduced into the liquid measuring container 110 in one go, or at least dropwise, from the pipette P, so that the measurement signal m of the weighing sensor 120 can be generated. S The processing unit 130 only indicates "stable" after pipette P has been completely emptied (see information on...). Figure 3 (Description). The liquid measuring container 110 is connected to the weighing sensor 120 in a force transmission manner so that it applies a gravitational force F acting on the weighing sensor 120. G The gravity F G As the measurement signal m S The signal is continuously output to the processing unit 130. The processing unit 130 is used to detect and process the measurement signal m from the weighing sensor 120. S And used to execute the program. Test result R P Output in the form of visual, auditory and / or electrical signals.

[0029] The introduced pipette liquid remains in the liquid measuring container 110, and with each further verification, the amount of liquid in the liquid measuring container increases. When the gravity F acting on the weighing sensor 120 of the liquid measuring container 110... GWhen the upper limit is reached, the processing unit 130 determines the upper limit based on the measurement signal m. S The upper limit is identified and a signal is sent to the user. The program runs continuously until the upper limit is reached; that is, the processing unit 130 continuously evaluates and processes the measurement signal m from the weighing sensor 120. S Therefore, the user only needs to fill the pipette with liquid volume V. P The liquid is introduced into the liquid measuring container 110, thereby triggering the measurement signal m of the weighing sensor 120. S This triggers the start of the verification process, as shown below. Figure 2 As stated above.

[0030] based on Figure 2 The measurement signal process will now be described in more detail. The measurement signal process is displayed before and after receiving the volume of liquid in the pipette to be verified, and is identified by instability or triggering of the measurement signal between time point t1 and time point t2.

[0031] This process begins with the user submitting the volume V of the liquid to be verified via pipette. P The liquid measurement container 110 is introduced to initiate the process. Triggering the measurement signal now initiates the measurement signal evaluation process. This is based on the most recent stable measurement point M. t1 The stable measurement signal m at time point t1 S The first gravity G is determined by the processing unit. t1 This gravity corresponds to the amount of liquid already present in the liquid measuring container 110. Based on the new stable measuring point M... t2 The stable measurement signal m at time point t2 S The second gravity G is determined by the processing unit 130. t2 This gravity corresponds to the amount of liquid already present in the liquid measuring container 110 plus the volume V of the liquid introduced into the pipette to be verified. P The sum of the volumes. The volume of liquid in the pipette, V. P Now we can use formula V P =ρ -1 ×(G t2 -G t1 )calculate.

[0032] Calculated liquid volume V in the pipette P Assigned with a defined nominal value V Ki Pipette volume rating K i The device can be pre-set to multiple volumes, for example, 20 μl, 100 μl, 200 μl, and 1000 μl, each with its own tolerance. Dispensing is performed to ensure that the pipette liquid volume V... P With the nominal value V KiThe absolute value of the volume difference ΔV should be as small as possible. Now we can check if the absolute value of the volume difference ΔV is within the nominal value V of the allocated pipette volume class Ki. Ki The volume difference ΔV is within the tolerance value T. When the volume difference ΔV is within the tolerance value T, the output as the test result will be released; otherwise, when the volume difference ΔV is outside the tolerance value T, a warning message will be issued.

[0033] When the measurement signal m S With a time-limited length t S And has the maximum signal difference or signal level Δm S When the signal is within the signal band S, it is processed by the processing unit 130 (see...). Figure 3 This indicates that the signal is stable. This means that, starting from this point in time when the measured signal value was measured, all measured signal values ​​over a previous time period could deviate by a defined difference at most. The constraints of these parameters significantly affect how the processing unit 130 determines a stable measurement point M. ti The speed. Here, it should be considered that the user should continuously supply the volume V of liquid in the pipette to be verified as much as possible. P The liquid is introduced into the liquid measuring container 110. Additionally, in the event of an unexpected interruption, the processing unit 130 should not prematurely (via parameter selection) release the measurement signal m. S The output is stable. At time t A Measurement signal m at point S It was not represented as stable because in the previous time period t S The signal described in the text is not always in signal band S. A Inside. Conversely, at time point t B Unlike the case at time t2, the signal m is measured at this time point. S It is represented as stable.

[0034] Furthermore, the program can also detect the previous time period Δt that terminated no later than time point t1. V The weight loss on the surface is used to process the measurement signal m S This allows for the determination of the evaporation rate c of the liquid present in the liquid measuring container 110. V Using this evaporation rate c V Now we can determine the evaporation volume V between time point t1 and time point t2. V Taking these values ​​into account, the volume of liquid in the pipette, V, can be calculated more accurately using the following formula. P V P =ρ -1 ×(G t2 -G t1 +c V ×(t2-t1)).

[0035] Evaporation rate cV The determination is always made using stable measurement signals after time point t2 and before time point t1, where the time interval Δt is... V The duration is at least and includes ten seconds, and / or at most and includes ten times the time difference between time point t1 and time point t2. In the time interval Δt... V In the middle, the evaporation rate c V The determination can also be carried out continuously. Based on the reference value, the evaporation rate c can be checked. V The effectiveness.

[0036] What might happen now is the gravitational difference ΔG t The value is less than the predetermined value. In this case, the program terminates without outputting any results. Additionally, the gravity F acting on the weighing sensor 120... G The value can be greater than the predetermined value; in this case, the program terminates and outputs a warning message. If these parameters are limited too narrowly to determine a stable measurement point M, the program will terminate. ti Then it is possible to measure signal m S Unable to achieve a stable state for the processing unit within the specified time period. The program then terminates and outputs a warning message.

[0037] Each predetermined volume can be displayed by three LEDs, for example, green, orange, and red. When a new result is output, the corresponding LED switches to a steady light for a certain period of time. After this period, the LED switches to a flashing mode, which further signals the result to the user, but also indicates that it is ready for the next test. When the liquid measuring container 110 is full, the result is displayed as described above, but additionally, all other LEDs flash in a short-on, long-off mode, for example, flashing red.

[0038] The procedure is fully automated and requires only user manipulation of the pipette. The device identifies the process and displays the results without any additional user interaction.

[0039] exist Figure 4 The diagram illustrates the calibration and verification intervals for pipettes. Pipettes are calibrated at the factory before being delivered to the user. Verification—also known as a quick test—is performed between two periodic calibrations according to the invention. It is recommended that the frequency of these quick tests be advised to the user through a risk assessment based on two specific criteria: A) the impact of pipetting on the user's business; and B) pipetting / pipetting process tolerances. From this, it can be deduced at what intervals the pipettes must be calibrated and what tolerances must be maintained during the pipetting process.

[0040] Between pipette calibrations, the procedure of this invention now provides immediate feedback to the user: the pipette remains sufficiently accurate and usable. If the feedback is negative, the pipette can be calibrated before the calibration interval expires. This early detection prevents serious disruption to the user's business.

[0041] Depending on the user's business needs, extending the calibration interval can also be considered to reduce more expensive calibration costs and reduce the time when pipettes are unavailable.

[0042] List of reference numerals

[0043] 110 Liquid measuring container

[0044] 120 Weighing Sensor

[0045] 130 processing units

[0046] P pipette

[0047] V P Pipette liquid volume

[0048] F G gravity

[0049] m S Measurement signal

[0050] G t1 First Gravity

[0051] M t1 Stable measurement point at time t1

[0052] G t2 Second gravity

[0053] M t2 Stable measurement point at time t2

[0054] Δt is the time period that determines the evaporation rate.

[0055] ρ is the density of the liquid in the pipette.

[0056] K i Pipette volume rating

[0057] VK i Grade nominal value

[0058] ΔV volume difference

[0059] T tolerance value

[0060] S, S A S B signal band

[0061] t Ssignal band duration

[0062] Δm S signal level

[0063] c V Evaporation rate

[0064] V V Evaporation volume

[0065] ΔG t Gravity difference

[0066] R P Test Results

Claims

1. A procedure for verifying pipettes, wherein, The verification result is a release or warning message, and the procedure includes the following steps: -supply Liquid measuring container (110) for receiving the volume V of liquid from the pipette to be verified. P , A weighing sensor (120) is connected to the liquid measuring container (110) by force transmission, the weighing sensor outputting the gravity F acting on the weighing sensor (120). G The corresponding measurement signal m S ,and Processing unit (130) for detecting and processing measurement signals m from weighing sensor (120) S ; -The processing unit (130) obtains the data from the nearest stable measurement point M. t1 Stable measurement signal m at time point t1 S Determine the first gravitational force G t1 Wherein, the nearest stable measurement point M t1 The volume of liquid in the pipettes awaiting verification is V in chronological order. P Before; -From the new stable measurement point M by the processing unit (130) t2 The stable measurement signal m at time point t2 S Determine the second gravity G t2 The new stable measurement point M t2 The volume of liquid in the pipettes awaiting verification is V in chronological order. P after; - The liquid volume V in the pipette is calculated by the processing unit (130) according to the following formula. P : V P =ρ -1 ×(G t2 -G t1 ); Where ρ is the density of the liquid in the pipette; -Calculate the volume of liquid V in the pipette. P Assigned to each with a defined nominal value V Ki At least two pipette volume classes K i One of them, wherein the dispensing performed by the processing unit (130) results in a pipette liquid volume V P With the nominal value V Ki The absolute value of the volume difference ΔV between them should be as small as possible; -The absolute value of the volume difference ΔV is tested by the processing unit (130) to see if it falls within the allocated pipette volume class K. i The nominal value of the grade V Ki Within the tolerance value T; and - The test result R is output by the processing unit (130). P , When the volume difference ΔV is within the tolerance value T, the output is release, or When the volume difference ΔV is outside the tolerance value T, a warning message is output.

2. The procedure according to claim 1, characterized in that, The test is performed by the processing unit (130) based on the received volume V of the liquid in the pipette to be verified. P The scheduled number of times will be carried out.

3. The procedure according to claim 1 or 2, characterized in that, Stable measurement signal m S From the measurement signal m S Within a limited time length t L and signal level Δm S The signal band S is used to determine this.

4. The procedure according to claim 1 or 2, characterized in that, The procedure is fully automated, wherein the volume V of the liquid in the pipette to be verified is... P The processing unit (130) triggers a verification process upon receiving a liquid measurement container (110), wherein, after outputting the test result, the processing unit (130) prepares to receive and verify the next pipette liquid volume V to be verified. P .

5. The procedure according to claim 3, characterized in that, The procedure is fully automated, wherein the volume V of the liquid in the pipette to be verified is... P The processing unit (130) triggers a verification process upon receiving a liquid measurement container (110), wherein, after outputting the test result, the processing unit (130) prepares to receive and verify the next pipette liquid volume V to be verified. P .

6. The procedure according to any one of claims 1-2 and 5, characterized in that, The procedure also includes the following steps: - By processing the previous time period Δt that terminates no later than time point t1 V Measurement signal m S To determine the evaporation rate c of the liquid in the liquid measuring container (110). V ; - Calculate the evaporation volume V between time point t1 and time point t2. V ;as well as - Calculate the liquid volume V in the pipette using the following formula. P : V P =ρ -1 ×(G t2 -G t1 +c V ×(t2-t1)).

7. The procedure according to claim 3, characterized in that, The procedure also includes the following steps: - By processing the previous time period Δt that terminates no later than time point t1 V Measurement signal m S To determine the evaporation rate c of the liquid in the liquid measuring container (110). V ; - Calculate the evaporation volume V between time point t1 and time point t2. V ;as well as - Calculate the liquid volume V in the pipette using the following formula. P : V P =ρ -1 ×(G t2 -G t1 +c V ×(t2-t1)).

8. The procedure according to claim 4, characterized in that, The procedure also includes the following steps: - By processing the previous time period Δt that terminates no later than time point t1 V Measurement signal m S To determine the evaporation rate c of the liquid in the liquid measuring container (110). V ; - Calculate the evaporation volume V between time point t1 and time point t2. V ;as well as - Calculate the liquid volume V in the pipette using the following formula. P : V P =ρ -1 ×(G t2 -G t1 +c V ×(t2-t1)).

9. The procedure according to claim 6, characterized in that, Time period Δt V It is at least and includes ten seconds, and / or at most and includes ten times the time difference between time point t1 and time point t2.

10. The procedure according to claim 7 or 8, characterized in that, Time period Δt V It is at least and includes ten seconds, and / or at most and includes ten times the time difference between time point t1 and time point t2.

11. The procedure according to claim 6, characterized in that, Check the evaporation rate c based on the reference value. V The effectiveness.

12. The program according to any one of claims 7-9, characterized in that, Check the evaporation rate c based on the reference value. V The effectiveness.

13. The procedure according to claim 10, characterized in that, Check the evaporation rate c based on the reference value. V The effectiveness.

14. The procedure according to any one of claims 1-2, 5, 7-9, 11, and 13, characterized in that, When the gravity difference ΔG t When the value is less than the predetermined value, the program terminates without outputting any results.

15. The procedure according to any one of claims 1-2, 5, 7-9, 11, and 13, characterized in that, When the gravity F acting on the weighing sensor (120) G If the value exceeds the predetermined value, the program terminates and outputs a warning message.

16. The procedure according to any one of claims 1-2, 5, 7-9, 11, and 13, characterized in that, If the measured signal m S If a stable state is not reached within the specified time period, the program terminates and outputs a warning message.

17. The procedure according to any one of claims 1-2, 5, 7-9, 11, and 13, characterized in that, Test results are output in the form of visual, auditory, and / or electrical signals.

18. The procedure according to claim 17, characterized in that, For each pipette volume class K i The test results are output as visual signals using multi-color LEDs.

19. The procedure according to claim 18, characterized in that, After the test results are output and after the limited output period of the visual signal, all LEDs flash simultaneously to signal that the verification has ended and to prepare for another verification.

20. The procedure according to any one of claims 1-2, 5, 7-9, 11, 13, 18-19, characterized in that, The procedure also includes the following steps: -supply Identification sensors for identifying pipettes, and A database system used to store and verify test results; - Detect the identification features of the pipette, and use the identification features to uniquely and accurately identify the pipette; - Store the test results of pipette verification in the database system.

21. An apparatus (100) for verifying a pipette, comprising: - Liquid measuring container (110), for receiving the volume V of liquid from the pipette to be verified. P , A weighing sensor (120) is connected to the liquid measuring container (110) by force transmission, the weighing sensor (120) outputting the gravitational force F acting on the weighing sensor (120). G The corresponding measurement signal m S ,as well as - Processing unit (130) for detecting and processing the measurement signal m from the weighing sensor (120) S To execute the procedure according to any one of claims 1-20.

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