Pipettor leakage detection device, method and system

Abstract

The invention provides a pipettor leakage detection device, method and system. The device comprises a leak detection device, an integrated image capturing module and an environment sensor, imaging parameters are dynamically adjusted to carry out high-definition multispectral imaging on liquid drops suspended at the bottom of the suction head, and the sealing failure degree is analyzed and quantified in combination with liquid drop oscillation. The method comprises the following steps: distributing liquid by stages after liquid absorption, returning 90% of the liquid to a liquid storage device, and retaining 10% of the liquid to form liquid drops; and extracting liquid drop characteristics based on an airflow disturbance test and multispectral imaging, judging leakage if the liquid drop is missing or the area is smaller than a threshold value, triggering self-cleaning, generating a traceability report, and feeding back data to optimize a judgment threshold value. The system integrates a multi-channel pipetting head, a leakage detection device and a data processing center, images and pressure signals are subjected to cross validation through data fusion, and a motion control module is driven to execute a decision closed loop (pipetting is suspended during leakage, and micro leakage is remeasured). The full-time-history leakage detection of the multi-channel pipettor is realized, 384-channel detection is less than or equal to 8 seconds, and the high-throughput detection reliability is remarkably improved.

Description

Technical Field

[0001] The present invention relates to the field of small-volume liquid pipetting using air displacement pipetting technology, and in particular to a pipette leakage detection device, method and system. Background Art

[0002] Leaks can occur at various locations within the pipetting channels of an air-displacement pipette, the most common location being at the interface of the disposable tip. A common method of attaching disposable tips is to use a machined metal or plastic extension (which may be called a "bullet" or "cone") that fits over the top of the pipette tip. The pipette tip is pushed onto this extension using a certain degree of force, and the more flexible pipette tip deforms slightly against the stiffer metal extension, creating an airtight seal. If a pipette tip malfunctions and does not provide a strong, reliable seal, some liquid may still be pipetted, but the actual amount pipetted may be less than the selected or set amount, potentially leading to errors in that part of the scientific experiment. If a multichannel pipette is used, the failure of any single tip in all channels being used can adversely affect the experimental results.

[0003] In some cases, it's possible to visually inspect the tips before the pipetting process is complete to confirm that all tips used in a multichannel pipette have been properly aspirated. However, this isn't a practical solution, requiring constant human attention, and many pipettes require repetitive, automated operations over extended periods of time. Furthermore, it's difficult for a human to clearly see all the tips in a multichannel pipette. For example, 96-channel liquid handling heads arranged in an 8x12 grid are very tightly spaced, making it difficult for an operator to easily visualize their spatial locations within the liquid handler. Within the same footprint, 384-channel liquid handling heads arranged in a 16x24 grid are even more densely packed, making it nearly impossible to view all 384 tips. Current leak detection technologies use pressure- or vacuum-based devices to monitor seal integrity. These methods require additional time to detect leaks, reducing their practicality for leak detection during every pipetting operation. Furthermore, these methods can be difficult or impossible to use with multichannel pipettes. Therefore, it would be desirable to have a leak detection system or method that checks the integrity of each pipetting stroke to ensure accurate pipetting volumes for large liquid transfers without requiring the additional time and effort of an automated system.

[0004] Chinese patent document CN220626389U discloses "an automatic heparin potency detection platform", which includes a detection table, the rear side of which is bolted to a mechanical lifting and adjusting arm on the top of the detection table. By setting a tip storage and sterilization mechanism, the mechanical lifting and adjusting arm on the top of the detection table is used to suspend the multi-channel pipette for lifting and lowering. Then, the plugged-in tips at the bottom of the multi-channel pipette are used to aspirate the heparin to be tested, and then placed in a constant temperature oscillator for testing. At the same time, before the tips are plugged into the bottom of the multi-channel pipette for use, they are stored and placed in a tip placement assembly on the left side of the top of the detection table. During this process, the tips inside the tip placement assembly are blown and dried by a drying assembly on the front side of the tip placement assembly. The above technical solution focuses on drying and sterilizing the tips during the storage stage, completely ignoring the risk of sealing failure during the pipetting operation; and its degree of automation is low and relies on manual intervention. Summary of the Invention

[0005] The present invention proposes a pipette leakage detection device, method and system, aiming to provide a detection solution through image capture and analysis, combined with environmental adaptation and dynamic adjustment mechanism, to achieve independent and real-time leakage detection of each tip of a multi-channel pipette, solve the problem of online detection of full-time sealing leakage of multi-channel pipettes, break through the limitations of low efficiency of traditional pressure detection methods and non-quantifiable static visual methods, and be suitable for leakage monitoring and quality control in high-throughput pipetting scenarios (such as 96 / 384-channel pipettes).

[0006] The purpose of the present invention also includes providing a pipette leakage detection device, including a multispectral image capture module, an environmental sensor and a processing unit, which captures the droplets hanging at the bottom of the pipette tip by dynamically adjusting the imaging parameters, and quantifies the degree of sealing failure in combination with the droplet oscillation analysis. A pipette leakage detection method is provided, which includes distributing a trace amount of liquid to form droplets after aspiration, extracting droplet characteristics based on airflow disturbance testing and multispectral imaging; if the droplets are abnormal, the pipetting is suspended, self-cleaning is triggered and a traceability report is generated, and feedback data is used to optimize the judgment threshold. A pipette leakage detection system is provided, which integrates a pipette head, a leakage detection device and a data processing center, cross-validates the leakage signal through data fusion, and drives the motion control module to execute a decision closed loop. This patent is committed to improving the reliability, automation and maintenance convenience of leak detection. By building a system that includes modules such as image capture, environmental perception, data processing, and self-cleaning, combined with methods such as phased liquid distribution and micro-vibration response analysis, leaks can be accurately determined and the degree of seal failure can be quantified. At the same time, automatic cleaning, fault alarms, and predictive maintenance after detection can be achieved, reducing manual intervention, optimizing detection thresholds, ensuring the accuracy of pipetting volumes, and guaranteeing the validity of experimental results, thus meeting the needs of efficient and precise leak detection in automated pipetting operations.

[0007] To achieve the above objectives, the present invention proposes a pipette leakage detection device: the leak detection device 5 includes an image capture module that performs multispectral imaging of the bottom of the pipette tip 2; the environmental sensor monitors the ambient temperature, humidity and vibration interference and feeds back to the image capture module; the processing unit is configured to control the multi-channel pipette to distribute part of the liquid after aspiration to form hanging droplets 7 at the bottom of the pipette tip 2, and independently perform droplet detection on each pipette tip 2; the imaging parameters are dynamically adjusted according to the environmental data, and the leakage judgment threshold is corrected based on the image analysis of the droplet morphology and the correlation with the environmental data.

[0008] Preferably, the leak detection device 5 also integrates a self-cleaning mechanism: after the detection is completed, inert gas is sprayed to remove residual droplets to prevent residual liquid from interfering with subsequent detection; the lens protection cover opens and closes in a linked manner to avoid liquid contamination and ensure the long-term stable operation of the image capture module.

[0009] Preferably, the processing unit controls the multi-channel pipette to perform phased liquid distribution: first, the maximum set volume of liquid is aspirated in the aspiration operation; 90% of the volume of liquid is distributed back to the liquid reservoir 4, and 10% of the volume is reserved for forming the hanging droplets 7, which not only reduces liquid waste but also ensures stable formation of the droplets; the droplet formation process is monitored in real time. If the droplets are not stably formed or missing within the set time, it is determined in advance that there is a leak and the pipetting operation is suspended, triggering a leak alarm to avoid experimental errors caused by continuing to pipette in a leaking state.

[0010] Preferably, the processing unit also works in conjunction with the motion control module to send a micro-vibration command with a frequency of 1-10 Hz to the multi-channel pipetting head 1. The image capture module captures the droplet oscillation response and quantifies the degree of seal failure based on the resonant frequency offset. This not only determines whether a leak is present, but also assesses the severity of the leak, providing an accurate basis for maintenance.

[0011] Preferably, the image capture module includes a high-resolution camera and lens, configured to simultaneously capture array images of all tips 2 in a multi-channel pipette, thereby realizing multi-channel parallel detection, improving detection efficiency, and being suitable for rapid detection of high-density channel pipettes.

[0012] Based on the above-mentioned pipette leakage detection device, the present invention proposes a pipette leakage detection method, comprising: S1: Controls the multichannel pipette tip to absorb liquid and then distributes a small amount of liquid to form hanging droplets; S2: Select whether to enable the airflow disturbance test mode to eliminate external interference, ensure that the test results are not affected by ambient airflow, and improve the reliability of the judgment; S3: The image capture module captures the bottom image of the pipette tip, pre-processes the image, and extracts the droplet contour and area features to provide a quantitative basis for leakage determination; S4: If the droplet area is lower than the set threshold or is not detected, pipetting is suspended, the seal is determined to have failed, the self-cleaning mechanism is triggered to remove the residue, and a traceability report is generated to facilitate tracing the source of the problem; S5: Feedback the test results to the data processing center, update the sealing performance database and optimize the subsequent judgment thresholds, so that the detection system can continuously adapt to the actual situation and improve long-term detection accuracy.

[0013] Preferably, the data processing center cross-validates the droplet profile feature image data and the pipetting head pressure sensor signal: the pressure signal fluctuation and droplet deformation are correlated and analyzed to quantify the leakage path and improve the accuracy of leak location; if the leak is not repaired, the corresponding channel is disabled and marked for maintenance to prevent the faulty channel from continuing to be used and affecting the experiment.

[0014] Preferably, the traceability report drives predictive maintenance: generates seal wear levels based on historical leakage frequencies; links a graded alarm system to trigger audible and visual alarms or automatic shutdowns according to the severity of the leakage, achieving differentiated early warnings; triggers a self-cleaning mechanism to remove residual droplets to keep the equipment clean; and feeds back sealing performance data to the database to optimize the judgment threshold, continuously improving the adaptability of the detection system.

[0015] The present invention also provides a pipette leakage detection system, comprising: The piston drive unit of the multi-channel pipetting head is controlled by the motion control module, which generates hanging droplets after aspirating liquid, providing detection objects for leak detection; The leak detection device's environmental sensors monitor temperature and humidity in real time, compensating for the image capture module's exposure parameters to ensure stable image quality. The data processing center integrates image data with the pipetting head pressure signal and outputs a decision through the leakage determination unit, thus improving the comprehensiveness and accuracy of the determination. The motion control module responds to the decision-making instructions: if normal, it positions the pipetting head to the target container to dispense the liquid; if there is a leak, it pauses the pipetting and activates the self-cleaning mechanism to remove the residue, stopping the loss in time and avoiding contamination.

[0016] Preferably, the data processing center performs closed-loop control, including: After receiving the leakage judgment result, it is fed back to the piston drive unit to adjust the liquid separation pressure and optimize the droplet formation conditions; When a slight leak occurs, the control motion module is repositioned to the leak detection device for retesting to reduce misjudgment; After the self-cleaning mechanism completes the residue removal, it sends a ready signal to the data processing center to unlock the pipetting process, realize the closed loop of the automated process, and improve operational efficiency.

[0017] Compared with the prior art, the present invention has the following beneficial effects: 1) Comprehensive and reliable leak detection: The system can independently perform droplet detection on each tip of a multi-channel pipette. The image capture module performs multispectral imaging of the tip bottom, dynamically adjusts imaging parameters based on environmental sensor data, and accurately analyzes droplet morphology. This allows for comprehensive leak detection in each channel, preventing experimental results from being affected by leaks in individual channels. For example, in multi-channel pipetting experiments, leak channels can be precisely located to prevent erroneous data. The processing unit is linked to the motion control module to send micro-vibration commands. By capturing the droplet oscillation response and resonant frequency offset, the degree of seal failure can be quantified, providing a more accurate basis for evaluating pipette sealing performance and helping to promptly identify potential leak risks. 2) Improve pipetting accuracy and experimental reliability: Monitor droplet formation in real time during the pipetting process. If droplet formation fails to stabilize or is missing within the set time, detect leakage in advance and suspend the operation to prevent inaccurate pipetting volumes from entering the experiment and ensure the reliability of experimental data. The data processing center cross-validates droplet profile feature image data with pipetting head pressure sensor signals to quantify leakage paths, further improving the accuracy of leak detection and providing more reliable support for experiments. 3) Self-cleaning and maintenance functions: The leak detection device has an integrated self-cleaning mechanism. After the test is completed, inert gas is sprayed to remove residual droplets. The lens protection cover opens and closes in a coordinated manner to prevent liquid contamination, keep the detection device clean, ensure the accuracy of subsequent tests, and reduce the workload of manual cleaning. Traceability reports drive predictive maintenance, generate seal wear levels based on historical leak frequencies, and link to a graded alarm system. According to the severity of the leak, the corresponding alarm or automatic shutdown is triggered, providing timely maintenance reminders, reducing the risk of equipment failure, and extending the service life of the pipette. 4) Optimize the detection process and judgment threshold: The data processing center implements closed-loop control, adjusts the dispensing pressure based on the leak judgment results, and re-positions and retests for minor leaks to ensure the accuracy of the test results and reduce false positives. Feedback of test results to the data processing center updates the sealing performance database and optimizes subsequent judgment thresholds, allowing the detection system to continuously adapt to the characteristics of different pipettes, improving the adaptability and accuracy of detection. 5) High compatibility and convenience: Compatible with any available brand or model of fully automatic multi-channel pipettes or liquid handling systems, with a wide range of applications; and the detection process does not require operators to spend additional time and energy, with a high degree of automation and convenient operation. It can automatically check the integrity of each pipetting action, improving work efficiency. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 Schematic diagram of a pipette leakage detection device provided in Example 1 of the present invention.

[0019] Figure 2 This is a flow chart of a pipette leakage detection method provided in Example 2 of the present invention.

[0020] Figure 3 This is a schematic diagram showing the completion of tip loading.

[0021] Figure 4 Schematic diagram of the pipetting head positioned to the reservoir.

[0022] Figure 5 It is a schematic diagram of the pipette tip immersed in liquid.

[0023] Figure 6 Schematic diagram of the pipetting head being positioned on the leak detection device and droplet formation.

[0024] Figure 7 This is a comparison image of normal droplet distribution and abnormal droplet absence.

[0025] Figure 8 Schematic diagram of the pipetting head positioned to the target container.

[0026] Figure 9 is a schematic diagram of liquid dispensing into a target container.

[0027] Figure 10 This is a block diagram of a pipette leakage detection system provided in Example 3 of the present invention.

[0028] In the figure, 1. Multichannel pipette head; 2. Pipette tip; 3. Pipette tip rack; 4. Liquid reservoir; 5. Leak detection device; 6. Target container; 7. Hanging drop; 8. Missing drop. DETAILED DESCRIPTION

[0029] In order to make the objectives, technical solutions and advantages of the present invention more clear, the technical solutions of the present invention are further described in detail below through examples and in conjunction with the accompanying drawings. It should be understood that the specific implementation scheme described here is only an optimal embodiment of the present invention and is only used to explain the technical solution of the present invention. It does not limit the scope of protection of the present invention. All other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0030] Air-displacement pipettes are used for pipetting small volumes of liquid (also known as aspirating and dispensing liquids), with typical volumes ranging from 1 μL to 5 mL. Air-displacement pipettes are based on a proven design that uses a moving piston within a cylinder, which can be machined, injection-molded, or similarly constructed. This cylinder is attached to a pipette tip (the pipette tip), which can be immersed in a container of liquid. When the piston is withdrawn from the nozzle, a partial vacuum (or lower pressure) is created within the cylinder chamber, causing the liquid to rise into the nozzle according to the ideal gas law—a process known as the aspiration step. The tip can then be removed from the liquid container; the liquid remains within the tip and is prevented from dislodging due to the partial vacuum within the cylinder chamber above the tip. After the aspiration step, the tip can be lifted from the source liquid container and moved to another location, such as a destination container, while retaining the liquid in the tip. When the tip is above the destination container, the piston can be moved downward toward the tip, increasing the air pressure between the piston and the liquid inside the tip, allowing the liquid to be dispensed from the tip into the destination container.

[0031] Air displacement pipettes can be configured to pipette one liquid sample at a time or to pipette multiple liquid samples simultaneously through parallel operation. When pipetting multiple samples simultaneously, a multichannel pipette is typically used. Each channel of a multichannel pipette has a disposable tip. Multichannel pipettes can have a range of channel numbers, with typical examples being 8 tips, 96 tips, and up to 384 tips, used in parallel in arrays of 1×8, 8×12, and 16×24, respectively. Whether using a single-channel or multichannel pipette, the entire pipetting mechanism is required to have an airtight seal, otherwise the integrity of the partial vacuum used for pipetting will be compromised, resulting in variations or errors in the actual aspirated volume.

[0032] Leaks can occur at various locations within the pipette channel in a pipette, such as around the sealing O-ring that moves the piston. However, the most common leak location is at the interface of the disposable tip, which is mechanically connected to the piston channel. Methods for attaching disposable tips vary, but a common method uses a machined metal or plastic extension (which may be called a "bullet" or "cone") that fits over the top of the pipette tip. The pipette tip is pushed onto this extension using a certain degree of force, and the more flexible pipette tip slightly deforms against the stiffer metal extension, forming an airtight seal. This airtight seal can be compromised for any particular tip for a variety of reasons, including but not limited to misaligned tip placement (or bending), variations in loading force, dimensional changes in the tip, or contamination between the tip and extension.

[0033] If a pipette tip malfunctions and fails to provide a secure, reliable seal, some liquid may still be pipetted, but the actual amount pipetted may be less than the selected or programmed amount, potentially leading to errors in that portion of the scientific experiment. If the malfunction is not immediately detected, it can be difficult or impossible to determine the source of the error, or in the worst case, it may go unnoticed, potentially invalidating the results of the scientific experiment. If a multichannel pipette is used, a malfunction in any single tip across all channels in use can adversely affect the experimental results.

[0034] In some cases, pipette operators can visually inspect the tips before the pipetting process is complete to confirm that liquid has been properly aspirated from all tips used in a multichannel pipette. However, this is not a practical solution, requiring constant human attention, and many pipettes require repetitive automated operations over extended periods of time. Furthermore, it can be difficult for a human to clearly see all the tips in a multichannel pipette. For example, 96-channel liquid handling heads arranged in an 8×12 grid are very closely spaced, making it difficult for operators to easily visualize their spatial locations within the liquid handler. Within the same footprint, 384-channel liquid handling heads arranged in a 16×24 grid are even more densely packed, making it nearly impossible to view all 384 tips. Current leak detection technologies use pressure- or vacuum-based devices to monitor seal integrity. These methods require additional time to detect leaks, reducing their practicality for leak detection during every pipetting operation. Furthermore, these methods can be difficult or impossible to use with multichannel pipettes. Therefore, it would be desirable to have a leak detection system or method that can check the integrity of each pipetting action so that the pipetting volume is accurate when transferring large amounts of liquid, without the need for an automated pipette leak detection system that takes additional time and effort.

[0035] Example 1: Figure 1 The present invention provides a pipette leak detection device comprising an image capture module, an environmental sensor, and a processing unit. The core component of the leak detection device (5) is the image capture module, which includes a high-resolution camera and lens equipped with a polarizing filter to eliminate liquid reflection interference. With a spatial resolution of 20 μm, it can simultaneously capture clear multispectral images of the bottoms of up to 384 pipette tips (2) in a multichannel pipette, enabling multi-channel parallel detection and improving detection efficiency. This device is suitable for rapid detection of high-density channel pipettes. The environmental sensor monitors ambient temperature, humidity, and vibration interference and provides feedback to the image capture module.

[0036] The processing unit is configured to control the multichannel pipette to dispense a portion of the liquid after aspiration to form a hanging droplet 7 at the bottom of the pipette tip 2. Droplet detection is performed independently for each pipette tip 2. Imaging parameters are dynamically adjusted based on environmental data, and the leak detection threshold is corrected based on image analysis of droplet morphology and correlation with environmental data. The processing unit controls the multichannel pipette head 1 to perform a precise liquid dispensing operation: first, aspirating the maximum set volume of liquid, then dispensing the liquid in stages—first dispensing 90% of the volume back into the reservoir 4 at high speed, then dispensing the remaining 10% at an extremely low speed of ≤1μL / second, so that the hanging droplet 7 forms stably at the end of the pipette tip 2. The processing unit also simultaneously activates a droplet formation monitoring timer. If a droplet fails to form within 500ms or shakes and falls off, a leak is immediately determined and the process is paused.

[0037] When the processing unit detects a suspected microleak, it sends a 1-10Hz micro-vibration command to the motion control module. This command captures the resonant frequency shift of the droplet 7 through an image sequence and, combined with the pressure sensor data, constructs a quantitative model for seal failure. For example, a frequency shift >5% corresponds to 30% O-ring wear. The leak determination result is output as a traceability report, including a leak heat map for tip 2 from the same batch, a predicted remaining seal life, and maintenance recommendations (such as "Replace the O-ring in channel 3"). This report is then fed back to the central database via the industrial bus to optimize global thresholds.

[0038] A common method of holding liquids is to use a disposable pipette tip to fix the liquid after aspirating and before dispensing the liquid. The common material for pipette tips is polypropylene. Compared with reusable fixed tips, the advantage of disposable pipette tips is that the pipetted liquid only comes into contact with the disposable tip and is discarded after each use, thus preventing any residue or contamination between samples between pipetting operations. Reusable fixed tips must be cleaned between each pipetting operation, and even the cleaning solution cannot guarantee the complete elimination of residues. Therefore, the use of disposable pipette tips is very common in various applications. In this patent, the tips can be selected as reusable fixed tips or disposable tips, and the selection is made according to actual conditions. The leak detection device 5 integrates a self-cleaning mechanism. If a reusable fixed tip is used, high-purity nitrogen gas will be automatically sprayed to remove residual droplets after the detection is completed, and the electric lens protection cover will be closed at the same time to prevent reagent splashes and contamination of optical components.

[0039] Example 2: Reference Figure 2 , the flow chart systematically describes a pipette leakage detection method provided by the present invention, comprising the following steps: S1: controlling the multi-channel pipette tip to absorb liquid and then distribute a trace amount of liquid to form hanging droplets; S2: Select whether to enable the airflow disturbance test mode to eliminate external interference, ensure that the test results are not affected by ambient airflow, and improve the reliability of the judgment; S3: The image capture module captures the bottom image of the pipette tip, pre-processes the image, and extracts the droplet contour and area features to provide a quantitative basis for leakage determination; S4: If the droplet area is lower than the set threshold or is not detected, pipetting is suspended, the seal is determined to have failed, the self-cleaning mechanism is triggered to remove the residue, and a traceability report is generated to facilitate tracing the source of the problem; S5: Feedback the test results to the data processing center, update the sealing performance database and optimize the subsequent judgment thresholds, so that the detection system can continuously adapt to the actual situation and improve long-term detection accuracy.

[0040] The data processing center cross-validates droplet profile feature image data and pipetting head pressure sensor signals: pressure signal fluctuations and droplet deformation correlation analysis are performed to quantify the leak path and improve the accuracy of leak location; if the leak is not repaired, the corresponding channel is disabled and marked for maintenance to prevent the faulty channel from continuing to be used and affecting the experiment.

[0041] The traceability report drives predictive maintenance: it generates seal wear levels based on historical leakage frequencies; it links a graded alarm system to trigger audible and visual alarms or automatic shutdowns according to the severity of the leak, achieving differentiated early warnings; it triggers the self-cleaning mechanism to remove residual droplets to keep the equipment clean; and it feeds back sealing performance data to the database to optimize the judgment threshold and continuously improve the adaptability of the detection system.

[0042] The above pipette leakage detection method is combined with Figure 3-9 The coherent operation diagram can be described as follows: first, the multi-channel pipetting head 1 is controlled to load the array of tips 2 from the tip rack 3 ( Figure 3 ), then positioned above the reservoir 4 ( Figure 4 ), descend and immerse in the liquid to complete the liquid suction operation ( Figure 5 After aspirating, the liquid is distributed in stages: 90% of the volume is quickly returned to the liquid reservoir 4, and 10% of the volume is retained for testing; then the pipette head 1 is moved above the leak detection device 5 ( Figure 6 ), a trace amount of liquid is distributed at a rate of ≤1μL / s to form a hanging droplet 7. At this time, the detection mode is selected based on the preset strategy: if the airflow disturbance test is enabled, a 0.2m / s controllable airflow is sprayed toward the droplet 7, and at the same time, a high-speed camera of 100fps is used to capture the droplet deformation displacement. A displacement of >50μm is judged as a seal failure; if the airflow test is disabled, multispectral imaging is directly started to obtain the droplet contour by penetrating the colored liquid through the near-infrared band. The image preprocessing step performs grayscale and adaptive binarization to extract the droplet projection area, contact angle and outer wall liquid film characteristics ( Figure 7This is a comparison of the normal droplet distribution and the abnormal droplet missing image. (b) The arrow on the right indicates the missing droplet 8); if the droplet area is less than 70% of the theoretical value or a residual liquid film is detected, the seal is judged to have failed and a three-level response is triggered: the pipetting operation is immediately suspended, a leak traceability report (including the coordinates of the fault channel and the historical failure curve) is generated, and the self-cleaning mechanism is activated to remove the residue. Regardless of the test results, the droplet morphology data is fed back to the sealing performance database, and the judgment threshold is dynamically optimized through the machine learning algorithm, such as automatically relaxing the contact angle tolerance by ±2° in a high temperature environment. After the test is completed, the multi-channel pipetting head 1 is positioned to the target container 6 and dispenses the liquid ( Figure 8-9 ), if the leak report shows a micro leak (such as a single channel failure), the system automatically marks the channel and skips it in subsequent operations, and notifies the maintenance system to prepare spare parts.

[0043] Figure 3 This diagram illustrates the key stages of tip loading: the tapered connector ("bullet") of the multichannel pipette head 1 forms a mechanical seal with the pipette tip 2, and the tip rack 3 is empty, ready for subsequent pipetting operations. At this point, the environmental sensor begins collecting laboratory temperature and humidity data, providing a baseline for imaging parameter adjustments.

[0044] Figure 4 This is a schematic diagram of the positioning of the pipette head to the liquid reservoir, showing that the pipette head 1 is precisely positioned directly above the liquid reservoir 4: the XYZ three-axis robotic arm moves the pipette head 2 array to a height of 1 cm above the liquid surface according to the preset coordinates. The piston drive unit is pre-pressurized and ready for liquid aspiration. The motion trajectory is calibrated in real time by the laser positioning sensor, and the positioning error is controlled within ±0.1mm.

[0045] Figure 5 It is a schematic diagram of the pipette tip immersed in liquid, showing the operational details of the pipette tip immersing in liquid: the pipette head 1 descends to immerse the pipette tip 2 2mm below the liquid surface in the liquid reservoir 4, the piston is withdrawn at a constant speed to generate negative pressure, and the set volume of liquid is sucked in; the embedded micro-pressure sensor synchronously monitors the pressure curve of each channel, and abnormal fluctuation data will be marked as a potential leakage risk point.

[0046] Figure 6 This is a schematic diagram of the pipetting head positioned on the leak detection device and droplet formation, revealing the core working state of the leak detection device 5: the pipetting head 1 carrying the liquid-containing pipette tip 2 is positioned on the imaging area of ​​the leak detection device 5, and after dispensing a trace amount of liquid, the suspended droplet 7 is stably suspended; at this time, the multispectral camera shoots the pipette tip array from below, the polarization filter eliminates the reflection of the polypropylene pipette tip, and the environmental sensor data compensates in real time for the change in the droplet surface tension caused by temperature fluctuations.

[0047] Figure 7 This is a comparison of the normal droplet distribution and the abnormal droplet missing image. Figure 7 (a) is the normal droplet distribution image, Figure 7(b) shows an image of an abnormal droplet absence, with the arrow on the right indicating a missing droplet 8. This comparison visually demonstrates the principle of the present detection method: Here, using a 96-channel pipette configured in an 8×12 grid array as an example, the present invention shows uniform hanging droplets 7 at the ends of all 96 tips 2 on the left, indicating a normal seal. The tip indicated by the arrow on the right shows a missing droplet 8, and the corresponding channel pressure data is synchronously abnormal, confirming O-ring failure through cross-validation. The image analysis algorithm automatically labels the fault coordinates (e.g., "channel B7"), providing a basis for precise maintenance.

[0048] Figure 8 This is a schematic diagram of the positioning of the pipetting head to the target container, showing the preparation for liquid dispensing after leak detection: the pipetting head 1 moves from the leak detection device 5 to above the target container 6, and the movement path avoids the marked fault channel; the self-cleaning mechanism sprays nitrogen to remove residual droplets, and the lens protection cover is closed to prevent contamination.

[0049] Figure 9 This is a schematic diagram of liquid distribution to the target container, showing the final liquid distribution: the pipette head 1 descends to a height of 1mm at the target container 6-well plate, and the piston is pressed down to distribute the liquid; for micro-leak channels, the system automatically reduces the distribution pressure by 20% to prevent liquid splashing, and at the same time records the channel performance degradation data for predictive maintenance.

[0050] Example 3: Figure 10 The present invention demonstrates a pipette leakage detection system. Based on the above-mentioned device and method, the main components of the system specifically include: a multi-channel pipette head 1 controls the aspiration and dispensing actions of the pipette tip 2 through a high-precision piston drive unit, and its conical connector is embedded in a micro-pressure sensor array to monitor the pressure changes on the sealing interface in real time; the leakage detection device 5 integrates an image capture module, an environmental sensor and a self-cleaning mechanism, and is fixed to the equipment platform by a rigid bracket; the data processing center includes a data fusion module, a leakage determination unit and a motion control interface, and runs on an industrial-grade real-time operating system; the motion control module drives the XYZ three-axis robotic arm to coordinate the motion trajectory of the pipette head 1 between the liquid reservoir 4, the leak detection device 5 and the target container 6.

[0051] The data processing center performs closed-loop control, including: After receiving the leakage judgment result, it is fed back to the piston drive unit to adjust the liquid separation pressure and optimize the droplet formation conditions; When a slight leak occurs, the control motion module is repositioned to the leak detection device for retesting to reduce misjudgment; After the self-cleaning mechanism completes the residue removal, it sends a ready signal to the data processing center to unlock the pipetting process, realize the closed loop of the automated process, and improve operational efficiency.

[0052] The following is a detailed description of each module: The piston drive unit of the multi-channel pipetting head 1 uses a closed-loop stepper motor with a displacement accuracy of 0.1μm. It switches to piezoelectric ceramic micro-drive mode when dispensing trace liquids. Controlled by the motion control module, it generates hanging droplets after aspirating liquid, providing a detection object for leak detection. The micro-pressure sensors on the surface of the conical connector are distributed in an 8×12 array with a sampling rate of 1kHz. If a pressure fluctuation of >5% is detected, an early warning is triggered.

[0053] The image capture module of the leak detection device 5 includes a high-resolution camera and lens, equipped with a polarizing filter to eliminate liquid reflection interference, and has a spatial resolution of 20μm. It can simultaneously perform clear multispectral imaging of the array image of the bottom of up to 384 tips 2 in a multi-channel pipette, realize multi-channel parallel detection, improve detection efficiency, and is suitable for rapid detection of high-density channel pipettes; multispectral imaging includes dual light sources of visible light and near-infrared (850nm), and the near-infrared band is specifically used for penetrating turbid liquid imaging; environmental sensor data is transmitted to the processing unit via the CAN bus, and the system is automatically triggered to pause when the temperature and humidity exceed the limit.

[0054] The data fusion module of the data processing center synchronously receives image data and pipetting head pressure signals. When visual inspection finds abnormal droplets, it retrieves the corresponding channel pressure history curve for time-frequency analysis. After confirming the leakage, it outputs a graded instruction: single-channel failure triggers a yellow alarm and skips the channel; multiple-channel failure triggers a red alarm and an emergency shutdown.

[0055] The motion control module uses a linear magnetic levitation guide rail to respond to the coordinate instructions of the data processing center with a positioning accuracy of ±5μm. If normal, it positions the multi-channel pipetting head 1 to the target container 6 to dispense liquid. If there is a leak, the pipetting is suspended and the self-cleaning mechanism is linked to remove the residue, stopping the loss in time and avoiding contamination. When the leakage judgment unit requires retesting, the stage lifting mechanism is controlled to adjust the height of the leak detection device 5 so that the camera focal length accurately matches the droplet position.

[0056] After receiving the cleaning instruction, the self-cleaning mechanism first sprays 30ms pulse nitrogen to remove droplets, and then starts the lens cover closing mechanism; the cleaning completion signal is fed back to the data processing center to unlock the pipetting process, and at the same time, the environmental parameters of this detection are updated to the sealing database.

[0057] In summary, the present invention proposes a pipette leakage detection device, method and system, which realizes full-time sealing monitoring in high-throughput pipetting scenarios through multi-spectral dynamic imaging and multi-source data fusion technology. The leak detection device 5 of Example 1 breaks through the limitations of traditional static detection and realizes micro-leakage quantification by combining environmental adaptation and micro-vibration analysis; the method flow of Example 2 constructs a "detection-decision-optimization" closed loop, and the airflow disturbance test and self-cleaning mechanism ensure the reliability of detection; the system-level integration of Example 3 coordinates data cross-validation and motion control to complete up to 384 channel detection within 8 seconds, and the false alarm rate is reduced to below 0.5%. Practical applications show that in CRISPR gene editing experiments, this solution reduces the data anomaly rate caused by pipetting leakage from 12.3% to 0.8%, and at the same time reduces the frequency of seal replacement by 40% through predictive maintenance, providing a solid foundation for high-throughput automated experiments.

[0058] The above is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. It should be pointed out that for ordinary technicians in this technical field, any easily conceivable changes or replacements without departing from the technical principles of the present invention should be covered within the scope of protection of the present invention.

Claims

1. A pipette leakage detection device, characterized in that: The leak detection device (5) includes an image capture module for performing multispectral imaging on the bottom of the suction tip (2); an environmental sensor for monitoring ambient temperature, humidity and vibration interference and feeding back the information to the image capture module; a processing unit for controlling a multichannel pipette to distribute a portion of liquid after aspiration to form hanging droplets (7) at the bottom of the suction tip (2), and independently performing droplet detection on each suction tip (2); and dynamically adjusting imaging parameters according to environmental data, and correcting a leakage determination threshold based on image analysis of droplet morphology and correlation with environmental data.

2. A pipette leakage detection device according to claim 1, characterized in that: The leak detection device (5) is also integrated with a self-cleaning mechanism: after the detection is completed, inert gas is sprayed to remove residual liquid droplets; the lens protection cover opens and closes in a linked manner to avoid liquid contamination.

3. A pipette leakage detection device according to claim 1, characterized in that: The processing unit controls the multi-channel pipette to perform phased liquid distribution: first, in the liquid aspiration operation, the maximum set volume of liquid is aspirated; 90% of the volume of the liquid is distributed back to the liquid reservoir (4), and 10% of the volume is reserved for forming the hanging droplets (7); the droplet formation process is monitored in real time. If the droplet is not stably formed or missing within the set time, it is determined in advance that it is a leak and the pipetting operation is suspended, triggering a leak alarm.

4. A pipette leakage detection device according to claim 1 or 3, characterized in that: The processing unit is also linked to the motion control module to send a micro-vibration instruction with a frequency of 1-10 Hz to the multi-channel pipetting head (1), capture the droplet oscillation response through the image capture module, and quantify the degree of sealing failure according to the resonance frequency offset.

5. A pipette leakage detection device according to claim 4, characterized in that: The image capture module includes a high-resolution camera and a lens, and is configured to simultaneously capture array images of all pipette tips (2) in the multi-channel pipette.

6. A pipette leakage detection method, characterized in that: include: S1: Controls the multichannel pipette tip to absorb liquid and then distributes a small amount of liquid to form hanging droplets; S2: Select whether to enable the airflow disturbance test detection mode to eliminate external interference; S3: The image capture module captures the bottom image of the pipette tip, pre-processes the image, and extracts the droplet contour and area features; S4: If the droplet area is lower than the set threshold or is not detected, pipetting is suspended, the seal is determined to be failed, the self-cleaning mechanism is triggered to remove the residue, and a traceability report is generated; S5: Feedback the test results to the data processing center, update the sealing performance database and optimize the subsequent judgment threshold.

7. A pipette leakage detection method according to claim 6, characterized in that: The data processing center cross-validates droplet profile feature image data and pipetting head pressure sensor signals: pressure signal fluctuations and droplet deformation correlation analysis are performed to quantify the leakage path; if the leak is not repaired, the corresponding channel is disabled and marked for maintenance.

8. A pipette leakage detection method according to claim 6, characterized in that: The traceability report drives predictive maintenance: generating seal wear levels based on historical leakage frequencies; linking a graded alarm system to trigger audible and visual alarms or automatic shutdowns based on leak severity; triggering a self-cleaning mechanism to remove residual droplets; and feeding back sealing performance data to a database to optimize judgment thresholds.

9. A pipette leakage detection system, characterized in that: The piston drive unit of the multi-channel pipetting head is controlled by the motion control module to generate hanging droplets after aspiration; The leak detection device's environmental sensors monitor temperature and humidity in real time and compensate for the image capture module's exposure parameters; The data processing center fuses the image data with the pipetting head pressure signal and outputs a decision through the leakage determination unit; The motion control module responds to the decision instruction: if normal, it positions the pipetting head to the target container to dispense the liquid; if there is a leak, it pauses the pipetting and activates the self-cleaning mechanism to remove the residue.

10. A pipette leakage detection system according to claim 9, characterized in that: The data processing center performs closed-loop control, including: After receiving the leakage judgment result, it is fed back to the piston drive unit to adjust the liquid separation pressure; When a slight leak occurs, the control motion module is relocated to the leak detection device for retesting; After the self-cleaning mechanism completes the residual removal, it sends a ready signal to the data processing center to unlock the pipetting process.

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