Single-channel pipette liquid level detection method and device based on embedded platform

Abstract

The invention relates to a single-channel pipette liquid level detection method and device based on an embedded platform, and the method comprises the steps: controlling a Z axis to enable a pipette to descend from a zero point, obtaining a first air pressure difference waveform of the pipette, and adjusting the speed parameter of the Z axis until the first air pressure difference waveform is in a stable state in the descending process; the Z axis is controlled to descend according to the speed parameters, so that the pipette extends into the liquid level, and a second air pressure difference waveform in the pipette is obtained; extracting liquid touching air pressure characteristics in the second air pressure difference waveform, and adding the extracted liquid touching air pressure characteristics into a reagent database; the Z axis is controlled to descend according to the speed parameter, a third air pressure difference waveform in the pipette is obtained, and when the characteristic of the third air pressure difference waveform is matched with the liquid touching air pressure characteristic, it is judged that liquid touching is conducted. The air pressure difference waveform characteristics replace the traditional air pressure threshold to judge whether the liquid is touched or not, so that the stability and adaptability of liquid level detection are improved, and a series of problems caused by detection failure in an extreme environment are effectively avoided.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to a method and device for detecting liquid level in a single-channel pipette based on an embedded platform. Background Technology

[0002] In the biomedical industry, the liquid level detection function of pipettes in automated pipetting workstations is crucial, primarily ensuring the accuracy and reliability of liquid transfer processes. Currently, automated pipettes used in the medical field typically employ two methods for liquid level detection: pressure sensors and capacitance sensors. Pressure sensors, because they do not rely on conductive tips, offer greater versatility and lower experimental costs. This method is compatible with both conductive and non-conductive tips, making it the most widely used liquid level detection method in automated pipettes.

[0003] However, existing liquid level detection methods rely on pressure thresholds to determine liquid contact. Their accuracy can be affected by the liquid's physical properties, such as viscosity and surface tension, which can vary significantly between different liquids. Furthermore, pressure sensor measurements are easily influenced by laboratory ambient pressure and temperature, as well as the Z-axis descent speed of the pipette during liquid level detection, potentially leading to decreased accuracy. This necessitates frequent manual adjustments of the pressure threshold based on varying experimental conditions and reagent types, increasing operational complexity and the possibility of human error. Moreover, for highly viscous liquids or those with extremely high surface tension, pressure signal abrupt changes may be insufficient, making it difficult to experimentally determine a single detection threshold. In short, current technology cannot enable automated pipettes to accurately detect liquid levels for different types of reagents simultaneously under various experimental conditions using pressure sensors.

[0004] Based on the above-mentioned technical problems, this application proposes a single-channel pipette liquid level detection method and device based on an embedded platform. Summary of the Invention

[0005] The purpose of this invention is to provide a single-channel pipette level detection method and device based on an embedded platform. This allows the embedded platform to experiment with new types of reagents using a pipette, acquiring data on the gas pressure difference waveform during the pipette tip's contact with the liquid, calculating characteristic data, and quickly establishing a corresponding gas pressure difference waveform database. Subsequently, once the type of reagent being detected is known, comparing the real-time gas pressure difference waveform characteristics acquired by the pipette with the database will determine whether a liquid level has been detected. Furthermore, as long as the pipette is connected to this embedded platform, the database can be shared, eliminating the need to repeat experiments for the same reagent.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows: A method for detecting liquid level in a single-channel pipette based on an embedded platform includes the following steps: Step S1. Plan Z-axis speed parameters: Control the Z-axis to make the pipette descend from the Z-axis zero point to the liquid surface at a uniform speed, obtain the air pressure difference between the inside of the pipette and the external environment in real time and generate the first air pressure difference waveform, adjust the Z-axis speed parameters until the first air pressure difference waveform is in a stable state during the descent of the pipette; Step S2. Collect liquid contact pressure data: Control the Z-axis to descend according to the speed parameters obtained in step S1 so that the pipette extends below the liquid surface, and obtain the pressure difference between the inside of the pipette and the external environment in real time and generate a second pressure difference waveform; Step S3. Build a reagent database: Extract the liquid contact pressure features from the second pressure difference waveform obtained in step S2, and add the extracted liquid contact pressure features into the reagent database; Step S4. Perform liquid level detection: Control the Z-axis to descend according to the speed parameters obtained in step S1, obtain the pressure difference between the inside and outside environment of the pipette in real time and generate a third pressure difference waveform, extract the features of the third pressure difference waveform and compare it with the liquid contact pressure features in the reagent database. When the features of the third pressure difference waveform match the liquid contact pressure features, it is determined that the liquid has been touched. Among them, the liquid contact pressure characteristics include the pressure step increment range, the acquisition time range of the pressure step waveform, the maximum step value range, the minimum step value range, and the step threshold band.

[0007] Furthermore, step S2 specifically includes: Step S21. Set the initial and final positions of the pipette. In the initial position, the pipette tip is above the liquid surface, and in the final position, the pipette tip is below the liquid surface. Calculate the displacement distance above the liquid surface and the displacement distance below the liquid surface. Step S22. Control the Z-axis to decrease according to the speed parameter obtained in step S1 to move the pipette from the initial position to the end position, and obtain the pressure difference between the inside of the pipette and the external environment in real time; Step S23. Determine the liquid contact time interval based on the ratio of the displacement distance of the pipette on the liquid surface to the displacement distance below the liquid surface, and generate a second gas pressure difference waveform from the gas pressure difference value within the liquid contact time interval; Step S24. Repeat steps S21-S23 to obtain multiple sets of second air pressure difference waveforms.

[0008] Furthermore, pressure calibration is performed before executing steps S1, S2, and S4. The pressure calibration steps are as follows: Step S01. By controlling the temperature, acquire multiple sets of temperature and pressure difference data inside the pipette, and calculate the temperature-pressure proportionality coefficient inside the pipette. ; Step S02. Obtain the current temperature inside the pipette. Calculate the calibration gas pressure difference inside the pipette. : .

[0009] Furthermore, the velocity parameters include initial velocity, acceleration during acceleration, constant velocity, acceleration during deceleration, and stopping velocity.

[0010] An apparatus for implementing any of the above-described single-channel pipette level detection methods based on an embedded platform, comprising: The Z-axis includes a lead screw linear module and a servo closed-loop motor. A pipette is mounted on the Z-axis. Inside the pipette are a temperature sensor and a differential pressure sensor. The differential pressure sensor includes a first detection port and a second detection port. The first detection port is connected to the inside of the pipette, and the second detection port is connected to the external environment. A pipette tip is detachably mounted on the pipette. The host computer, servo closed-loop motor, temperature sensor, and differential pressure sensor are all electrically connected to the host computer.

[0011] Furthermore, the servo closed-loop motor is equipped with an encoder.

[0012] Furthermore, the suction tip is a polypropylene plastic suction tip.

[0013] The technical solutions provided in this application have at least the following technical effects or advantages: 1. By using the waveform characteristics of air pressure difference to replace the traditional air pressure threshold to determine whether there is liquid contact, the stability and adaptability of liquid surface detection are improved, and a series of problems caused by detection failure in extreme environments are effectively avoided; 2. By using differential pressure calibration, the influence of temperature changes on differential pressure readings is eliminated, effectively offsetting the long-term drift of the sensor itself, environmental temperature drift, and slight volume differences caused by different batches of suction tips, ensuring the long-term detection accuracy and reliability of the equipment throughout its entire life cycle and under different usage conditions. 3. By building a reagent database, pipettes can quickly access the contact parameters of different reagents, are compatible with the physical properties of various experimental reagents, and save a lot of manpower and debugging costs before each experiment. Attached Figure Description

[0014] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0015] Figure 1 This is a schematic diagram of the differential pressure sensor mounting structure according to an embodiment of this application; Figure 2 This is a flowchart illustrating the process of an embodiment of this application; Figure 3 This refers to the air pressure reading under static conditions in the embodiments of this application. Figure 4 This is the air pressure reading under liquid contact conditions in the embodiments of this application.

[0016] Reference numerals: 1. Connector; 11. First channel; 12. Second channel; 2. Differential pressure sensor; 21. First detection port; 22. Second detection port. Detailed Implementation

[0017] To further illustrate the technical means and effects of the present invention in achieving its intended purpose, the following detailed description of the specific implementation methods, structures, features, and effects of the present invention, in conjunction with the accompanying drawings and preferred embodiments, is provided below.

[0018] Example 1 A single-channel pipette level detection device based on an embedded platform includes a hardware platform and a software platform. The hardware platform is an automated pipetting workstation, and the software platform is host computer software.

[0019] The automated pipetting workstation includes an X-axis, Y-axis, Z-axis, a pipette, and a host computer. The X, Y, and Z axes each include a lead screw linear module and a servo closed-loop motor. The pipette is mounted on the Z-axis, and the X, Y, and Z axes can drive the pipette to achieve three-dimensional positional movement. The servo closed-loop motor is equipped with an encoder, enabling precise control of the pipette's position and speed.

[0020] The pipette is detachably equipped with a polypropylene plastic pipette tip. The pipette has an integrated temperature sensor and a differential pressure sensor 2. The servo closed-loop motor, temperature sensor, and differential pressure sensor 2 are all electrically connected to the host computer to achieve data interaction.

[0021] like Figure 1 As shown, the differential pressure sensor 2 is mounted on the pipette via the connector 1. The differential pressure sensor 2 includes a first detection port 21 and a second detection port 22. The first detection port 21 is connected to the internal piston chamber of the pipette via the first channel 11 on the connector 1, and the second detection port 22 is connected to the external environment via the second channel 12 on the connector 1.

[0022] Differential pressure sensors use the external atmospheric pressure as a reference to directly measure the pressure difference between the inside and outside. They can automatically offset the fluctuations in ambient air pressure caused by factors such as weather changes, altitude, or laboratory ventilation. This makes initial calibration and periodic zeroing operations very simple and direct, reduces the difficulty of temperature compensation, and significantly improves the accuracy, repeatability, and reliability of fault diagnosis.

[0023] Example 2 like Figure 2 The method for detecting liquid level in a single-channel pipette based on an embedded platform, as shown, includes the following steps: First, set up the automated pipetting workstation as described in Example 1 and prepare the experimental reagents; in this example, alcohol is used. Prepare 20 polypropylene plastic pipette tips. Prepare one pipette tip box and one waste pipette tip box. Ensure the experimental reagent has a liquid level of 4 cm to facilitate the initial acquisition of the gas pressure difference waveform. Simultaneously, control the automated pipetting workstation via the host computer and calibrate the current liquid level to 4 cm.

[0024] Step S01. By controlling the temperature, obtain multiple sets of temperature and pressure difference data inside the pipette. Plot a scatter plot with temperature on the x-axis and pressure difference on the y-axis. Fit a straight line passing through the origin using linear regression. The slope of the straight line is the temperature-pressure ratio coefficient inside the pipette. ; Step S02. Obtain the current temperature inside the pipette. Calculate the calibration gas pressure difference inside the pipette. : .

[0025] This is because, in a closed system, if the volume remains constant while the temperature increases, according to Charles's Law, the gas pressure will increase with increasing temperature. This is because as the temperature rises, the kinetic energy of the gas molecules increases, leading to more frequent and stronger collisions between molecules, thus increasing the pressure on the container walls. Therefore, in this case, the higher the temperature, the higher the gas pressure.

[0026] According to the ideal gas law: After transformation, we get: In the formula, P represents pressure; V represents volume; n represents the amount of substance (number of moles); R is the ideal gas constant, which is approximately 8.314 J / (mol·K); and T represents the absolute temperature (in Kelvin).

[0027] When a pipette is not aspirating or dispensing liquid, the volume of air and the amount of substance inside the pipette can be considered constant. The proportional relationship between temperature T and pressure P can be expressed by R (ideal gas constant) in the ideal gas law. Since R is also a constant, it can be considered that... Treating it as a constant K, it is called the temperature-pressure proportionality coefficient. Thus: The pressure difference is obtained from the pressure difference between the inside and outside of the pipette. Therefore, the calibration gas pressure difference inside the pipette is... It can also be obtained using the formula above.

[0028] Step S1. Plan Z-axis speed parameters: Control the Z-axis to make the pipette descend from the Z-axis zero point to the liquid surface at a uniform speed, obtain the pressure difference between the inside of the pipette and the external environment in real time and generate the first pressure difference waveform, adjust the Z-axis speed parameters until the first pressure difference waveform is stable during the descent of the pipette.

[0029] Using the host computer to control the X, Y, and Z axes of the hardware platform, after attaching the pipette tip, move the pipette to a position 4 cm above the liquid surface and stop. Control the Z-axis to lift the pipette and return it to the Z-axis zero point. At this point, the pipette performs a self-calibration of air pressure. Figure 3 As shown, at room temperature (23℃), the reading fluctuates within ±20°C of 8190. This reading is the AD sampling reading of the differential pressure sensor and has not been converted to air pressure units. Real-time unit conversion using the formula would consume chip processing power. We only need to ensure that the reading range fed back by the differential pressure sensor inside the pipette is consistent with the sensor's calibration range. This reading is definitely a range because air pressure, as a physical quantity, will exhibit a certain degree of fluctuation and lag in actual measurement. This is the result of multiple factors acting together.

[0030] Once the pipette's air pressure self-calibration is successful, begin adjusting the Z-axis speed parameters. Adjust the initial velocity, acceleration during the acceleration phase, constant velocity, deceleration acceleration, and stopping velocity respectively, allowing the pipette to move vertically and uniformly from the Z-axis zero point to a position 4cm above the water surface. During this movement, measure the pressure difference reading in real time and upload it to the host computer to generate the first air pressure difference waveform. Observe the reading of the first air pressure difference waveform. If the fluctuation of the first air pressure difference waveform is too large, it indicates that the Z-axis speed curve is not stable enough during vertical downward movement, and the pipette is experiencing slight vibration, leading to unstable air pressure inside the pipette body. In this case, repeat step S1 until the air pressure difference waveform is stable during the Z-axis descent. Only then are the Z-axis speed parameters qualified, and these speed parameters will be used for each subsequent liquid surface detection.

[0031] This speed parameter is only related to the mechanical structure and the sensitivity of the differential pressure sensor. If the reagent is changed, step S1 does not need to be repeated.

[0032] Step S2. Collect liquid contact pressure data: Control the Z-axis to descend according to the speed parameters obtained in step S1 so that the pipette extends below the liquid surface, and obtain the pressure difference between the inside of the pipette and the external environment in real time and generate a second pressure difference waveform.

[0033] Using alcohol as the reagent, the current indoor temperature was first recorded as 23℃. The automated pipetting platform was then controlled by the host computer to position the pipette tip 4cm above the liquid surface and perform air pressure calibration. After air pressure calibration, a pipette tip contact test was performed.

[0034] The liquid contact test for pipette tips specifically includes: Step S21. Set the initial and final positions of the pipette. At the initial position, the pipette tip is 4 cm above the liquid surface, and at the final position, the pipette tip is 1 cm below the liquid surface. Step S22. Control the Z-axis to decrease by 5cm according to the speed parameter obtained in step S1, so that the pipette moves from the initial position to the end position, and obtain the air pressure difference between the inside of the pipette and the external environment in real time. Step S23. Determine the liquid contact time interval based on the ratio of the displacement distance of the pipette on the liquid surface to the displacement distance below the liquid surface, and generate a second gas pressure difference waveform from the gas pressure values ​​within the liquid contact time interval; Since the Z-axis moves at approximately a constant speed during the entire vertical descent process, the ratio of the displacement distance above the liquid surface to the displacement distance below the liquid surface is equal to the ratio of the displacement time above the liquid surface to the displacement time below the liquid surface, which is 4:1. Based on this time ratio, the contact time interval of the suction head can be determined. The air pressure reading within this time interval is then uploaded to the host computer to generate a second air pressure difference waveform.

[0035] The contact between the pipette tip and the liquid surface occurs instantaneously. Upon contact, a step-like change in the internal pressure difference waveform of the pipette tip occurs. For example... Figure 4 As shown, the waveform rises the instant the pipette tip contacts the liquid surface.

[0036] Step S24. Repeat steps S21-S23 to obtain multiple sets of second air pressure difference waveforms.

[0037] The second air pressure difference waveform needs to be measured 10 times, and the suction tip needs to be replaced after each experiment, and air pressure calibration needs to be performed at the beginning of each new experiment.

[0038] Step S3. Build a reagent database: Extract the liquid contact pressure features from the second pressure difference waveform obtained in step S2, and add the extracted liquid contact pressure features into the reagent database; The host computer generates characteristic data based on several collected second air pressure difference waveforms, including the air pressure step increment range when the suction head contacts the liquid surface, the collection time range of the air pressure step waveform, the maximum step value range, the minimum step value range, and the step threshold band.

[0039] The host computer generates a unique reagent code for the alcohol reagent and adds the aforementioned characteristic parameters to the database. For pipettes that have not stored reagent information, the host computer can send the relevant parameters uniformly without needing to perform a second experiment to obtain the parameters.

[0040] Step S4. Perform liquid level detection: Control the Z-axis to descend according to the speed parameters obtained in step S1, obtain the pressure difference between the inside and outside environment of the pipette in real time and generate a third pressure difference waveform, extract the features of the third pressure difference waveform and compare it with the liquid contact pressure features in the reagent database. When the features of the third pressure difference waveform match the liquid contact pressure features, it is determined that the liquid has been touched.

[0041] The host computer selects an alcohol reagent from the database and sends a command containing the alcohol reagent to the automated pipetting platform. The pipette then detects the liquid level based on the alcohol's characteristic parameters. During the detection process, if the pressure step increment range, the acquisition time range of the pressure step waveform, the maximum step value range, the minimum step value range, and the step threshold band at a certain time interval all match the parameter range of the reagent, then it is assumed that the pipette tip orifice has contacted the liquid level. At this point, the pipette's Z-axis motor stops abruptly, and the pipette simultaneously returns the detected alcohol level information to the host computer, informing it that the alcohol level has been detected.

[0042] The technical solutions provided in this application have at least the following technical effects or advantages: 1. By using the waveform characteristics of air pressure difference to replace the traditional air pressure threshold to determine whether there is liquid contact, the stability and adaptability of liquid surface detection are improved, and a series of problems caused by detection failure in extreme environments are effectively avoided; 2. By using air pressure calibration, the influence of temperature changes on differential pressure readings is eliminated, effectively offsetting the long-term drift of the sensor itself, environmental temperature drift, and slight volume differences caused by different batches of pipette tips, ensuring the long-term detection accuracy and reliability of the equipment throughout its entire life cycle and under different usage conditions. 3. By building a reagent database, pipettes can quickly access the contact parameters of different reagents, are compatible with the physical properties of various experimental reagents, and save a lot of manpower and debugging costs before each experiment.

[0043] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A method for detecting liquid level in a single-channel pipette based on an embedded platform, characterized in that, Includes the following steps: Step S1. Plan Z-axis speed parameters: Control the Z-axis to make the pipette descend from the Z-axis zero point to the liquid surface at a uniform speed, obtain the air pressure difference between the inside of the pipette and the external environment in real time and generate the first air pressure difference waveform, adjust the Z-axis speed parameters until the first air pressure difference waveform is in a stable state during the descent of the pipette; Step S2. Collect liquid contact pressure data: Control the Z-axis to descend according to the speed parameters obtained in step S1 so that the pipette extends below the liquid surface, and obtain the pressure difference between the inside of the pipette and the external environment in real time and generate a second pressure difference waveform; Step S3. Build a reagent database: Extract the liquid contact pressure features from the second pressure difference waveform obtained in step S2, and add the extracted liquid contact pressure features into the reagent database; Step S4. Perform liquid level detection: Control the Z-axis to descend according to the speed parameters obtained in step S1, obtain the pressure difference between the inside and outside environment of the pipette in real time and generate a third pressure difference waveform, extract the features of the third pressure difference waveform and compare it with the liquid contact pressure features in the reagent database. When the features of the third pressure difference waveform match the liquid contact pressure features, it is determined that the liquid has been touched. The liquid-contact gas pressure characteristics include the gas pressure step increment range, the gas pressure step waveform acquisition time range, the maximum step value range, the minimum step value range, and the step threshold band.

2. The single-channel pipette level detection method based on an embedded platform according to claim 1, characterized in that, Step S2 specifically includes: Step S21. Set the initial and final positions of the pipette. In the initial position, the pipette tip is above the liquid surface, and in the final position, the pipette tip is below the liquid surface. Calculate the displacement distance above the liquid surface and the displacement distance below the liquid surface. Step S22. Control the Z-axis to decrease according to the speed parameter obtained in step S1 to move the pipette from the initial position to the end position, and obtain the pressure difference between the inside of the pipette and the external environment in real time; Step S23. Determine the liquid contact time interval based on the ratio of the displacement distance of the pipette on the liquid surface to the displacement distance below the liquid surface, and generate the second gas pressure difference waveform from the gas pressure difference value within the liquid contact time interval; Step S24. Repeat steps S21-S23 to obtain multiple sets of second air pressure difference waveforms.

3. The single-channel pipette level detection method based on an embedded platform according to claim 1, characterized in that, Before performing steps S1, S2, and S4, pressure calibration is performed. The pressure calibration steps are as follows: Step S01. By controlling the temperature, acquire multiple sets of temperature and pressure difference data inside the pipette, and calculate the temperature-pressure proportionality coefficient inside the pipette. ; Step S02. Obtain the current temperature inside the pipette. Calculate the calibration gas pressure difference inside the pipette. : 。 4. The single-channel pipette level detection method based on an embedded platform according to claim 1, characterized in that, The speed parameters include initial velocity, acceleration during acceleration, constant velocity, acceleration during deceleration, and stopping velocity.

5. An apparatus for implementing the single-channel pipette level detection method based on an embedded platform according to any one of claims 1-4, characterized in that, include: The Z-axis includes a lead screw linear module and a servo closed-loop motor. A pipette is mounted on the Z-axis. The pipette contains a temperature sensor and a differential pressure sensor. The differential pressure sensor includes a first detection port and a second detection port. The first detection port communicates with the interior of the pipette, and the second detection port communicates with the external environment. A pipette tip is detachably mounted on the pipette. The host computer, the servo closed-loop motor, the temperature sensor, and the differential pressure sensor are all electrically connected to the host computer.

6. The apparatus for a single-channel pipette level detection method based on an embedded platform according to claim 5, characterized in that, The servo closed-loop motor is equipped with an encoder.

7. The apparatus for a single-channel pipette level detection method based on an embedded platform according to claim 5, characterized in that, The suction tip is a polypropylene plastic suction tip.

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