A bubble detection and prompt pipetting gun and a bubble processing method thereof

Abstract

The application discloses a bubble detection and prompt sample adding gun and a bubble treatment method thereof. In one aspect, the application provides a bubble detection and prompt sample adding gun, which comprises a sample adding gun body, a piston driving mechanism, a connecting pipe and function modules integrated thereon, wherein the function modules comprise a bubble visual detection module, a processing module, a man-machine interaction module and an execution module. In another aspect, the application provides a bubble treatment method applied to the sample adding gun, which comprises the following steps: S1: a user triggers an image acquisition step by pressing a detection key. After the sample adding gun completes sample suction, the bubble visual detection module is automatically started to acquire a liquid column image. The application can automatically and accurately detect and quantify the bubbles in the gun head, prompt to remove the bubbles and guide the operator to compensate for the lost liquid volume, so that the sample adding error caused by the bubbles is eliminated at the root, and the automation degree and the result reliability of the experiment are improved.

Description

Technical Field

[0001] This invention relates to the field of laboratory liquid handling equipment technology, specifically to a pipette capable of automatically detecting, quantifying, and prompting the removal of air bubbles in the pipette tip, and a method for removing air bubbles therefrom. Background Technology

[0002] In micro-volume sampling procedures in fields such as molecular biology and clinical testing, air bubbles aspirated into the pipette tip are a common problem affecting sampling accuracy. Air bubbles occupy the effective volume within the tip, causing the actual sample volume to be less than the set value, introducing experimental error. Currently, conventional de-bubbling methods rely on the operator visually observing and then manually tapping the pipette tip or re-absorbing the sample, which is inefficient and subjective.

[0003] Chinese patent document CN113441199B discloses a "sample dispensing gun for automatically removing air bubbles from a sample." This gun uses an ultrasonic vibration rod on one side of its body, with vibration transmitted through a vibration collar to a connecting tube, causing the pipette tip to vibrate and remove air bubbles. While this technical solution provides a physical method for defoaming, it has significant shortcomings: First, it lacks automatic detection; the presence or absence of air bubbles and the effectiveness of bubble removal rely entirely on visual judgment by the user, resulting in low intelligence. Second, the bubble removal process is open-loop, only performing vibration; it cannot detect whether air bubbles have actually been removed, nor can it quantify the liquid volume lost due to bubble expulsion, thus failing to guarantee the accuracy of sample dispensing after bubble removal. The actual liquid volume inside the pipette tip after vibration is unknown, potentially leading to the failure of subsequent experiments.

[0004] Therefore, there is an urgent need in the field for a sample addition device and method that can automatically and accurately solve the bubble problem and ensure the accuracy of the final sample volume. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the present invention aims to provide a pipette with bubble detection and alerting capabilities, along with a method for handling bubbles. This pipette can automatically and accurately detect and quantify bubbles within the pipette tip, alerting the user to remove bubbles and guiding the operator to compensate for lost liquid volume. This eliminates the pipetting error caused by bubbles at its source, improving the automation level and reliability of experimental results.

[0006] To solve the above-mentioned technical problems, the present invention adopts the following technical solution:

[0007] On the one hand, the present invention provides a sample dispenser for bubble detection and indication.

[0008] The sample dispensing gun includes a dispensing gun body, a piston drive mechanism, a connecting tube, and functional modules integrated thereon. These functional modules include a bubble visual inspection module, a processing module, a human-machine interaction module, and an execution module.

[0009] The bubble visual detection module includes an image sensor and a light source positioned on opposite sides, as well as a transparent observation window located on the side wall of the connecting tube. The image sensor (preferably a GC0308 SPI interface camera module) and the light source are positioned on either side of the observation window, forming a transmissive illumination path for automatically acquiring clear images of the liquid column inside the connecting tube and pipette tip after sample addition. Bubbles appear as shadows in the image due to differences in refractive index, making them easy to identify.

[0010] The processing module includes a microcontroller (such as an STM32G474RET6 microcontroller). This module connects to the bubble vision detection module and runs image processing algorithms to preprocess, threshold segment, and perform connected component analysis on the acquired images to identify bubble regions. More importantly, based on the known inner diameter of the connecting pipe—a fixed parameter—it calculates the actual cross-sectional area of ​​the identified bubble using pre-stored calibration relationships (conversion factors between pixel size and actual size). Then, it uses a geometric model (such as a cylinder or spherical cap model) to accurately calculate the bubble's volume. This volume represents the volume of liquid missing due to the presence of the bubble.

[0011] The human-computer interaction module includes a prompt module and a user input module.

[0012] The prompting module is connected to the processing module and is used to output compensation prompt information related to the calculated bubble volume. This module may include a display screen (such as an OLED) and / or a voice broadcasting unit (such as a SYN6288 chip) to display and broadcast the volume value to be compensated (e.g., "Please aspirate 2.3 μl").

[0013] The user input module is connected to the processing module and is used to receive user operation commands. The user input module includes at least one function key, such as a detection key, an execution key, and a cancel key. By operating different function keys, the user can actively trigger bubble detection, confirm the execution of debubbling, or cancel the current operation, achieving flexible human-machine collaborative control.

[0014] The debubbling execution module is connected to the processing module and is used to generate physical vibrations to remove bubbles upon receiving a command. It preferably adopts a direct-drive structure, where the piezoelectric ceramic transducer (PZT) is directly fixed to the outer wall of the connecting tube by means of bonding or other methods, and is driven by a dedicated piezoelectric drive chip (such as DRV8662). This structure features a short vibration transmission path, high efficiency, and a simplified structure.

[0015] On the other hand, the present invention provides a method for treating air bubbles applied to the above-mentioned sample gun.

[0016] This method realizes an intelligent closed-loop process from detection and decision-making to guided compensation. The steps are triggered and confirmed by the user through function keys, including the following steps:

[0017] S1: The user triggers the image acquisition step by pressing the detection button. After the sample is aspirated, the pipette automatically starts the bubble visual detection module to acquire the liquid column image.

[0018] S2: The processing module processes the image, identifies bubbles, and accurately calculates the bubble volume based on the known inner diameter of the connecting pipe.

[0019] S3: The prompt module immediately outputs bubble volume information and compensation prompts.

[0020] S4: The user presses the execute button as prompted to trigger the debubbling step. The debubbling execution module starts and removes bubbles through vibration.

[0021] S5: The system further outputs a clear value of the volume to be compensated, guiding the user to manually adjust the set volume of the pipette and re-absorb the liquid of the difference volume, thereby accurately restoring the initial target sample volume.

[0022] Compared with the prior art, the present invention has the following significant advantages:

[0023] 1. By integrating a machine vision module, it replaces the traditional subjective judgment of the human eye, and can automatically and objectively identify bubbles and accurately calculate their volume, solving the pain point of "not knowing whether they exist or how many there are".

[0024] 2. By calculating the bubble volume and generating compensation prompts, the operator is guided to accurately restore the set sample addition amount, thus achieving closed-loop control of the addition accuracy from the process perspective. This is something that existing devices with only defoaming functions cannot achieve.

[0025] 3. By combining visual display and voice prompts, the complex precision control process is simplified into clear user guidance, which lowers the operating threshold and improves work efficiency and user experience.

[0026] 4. The direct-drive vibration scheme, which integrates piezoelectric ceramic sheets directly into the connecting pipe, shortens the vibration transmission path, improves energy utilization efficiency and defoaming reliability, and simplifies the mechanical structure. Attached Figure Description

[0027] Figure 1 This is a schematic diagram of the structure of Embodiment 1 of the present invention.

[0028] Figure 2 This is a partial exploded view of Embodiment 1 of the present invention.

[0029] Figure 3 This is a circuit diagram of the power module according to Embodiment 1 of the present invention.

[0030] Figure 4 This is a circuit diagram of the processing module according to Embodiment 1 of the present invention.

[0031] Figure 5 This is a circuit diagram of the bubble visual detection module according to Embodiment 1 of the present invention.

[0032] Figure 6 This is a circuit diagram of the debubbling execution module according to Embodiment 1 of the present invention.

[0033] Figure 7 This is a circuit diagram of the prompt module and user input module according to Embodiment 1 of the present invention.

[0034] The following are the labels in the diagram: 1. Sample gun body; 2. Connecting tube; 21. Observation window; 3. Pipette tip; 4. Image sensor; 5. Light source; 6. Vibration actuator; 7. Control box; 8. OLED display screen; 9. Function buttons; 10. Setting buttons; 20. USB charging port; 30. Power switch. Detailed Implementation

[0035] The present invention will now be described in conjunction with the accompanying drawings. The specific embodiments described herein are for illustrative and explanatory purposes only and are not intended to limit the present invention. Various modifications and improvements to the technical solutions of the present invention made by those skilled in the art without departing from the spirit of the present invention should fall within the protection scope of the present invention.

[0036] Example 1

[0037] like Figures 1 to 7 As shown, this embodiment provides a dispensing gun with bubble detection and prompting. Based on the existing dispensing gun, this embodiment integrates a bubble visual detection module, a defoaming execution module, a processing module, a prompting module, and a user input unit.

[0038] The sample gun includes: a sample gun body 1, a piston drive mechanism located inside the body, a connecting tube 2 located at the bottom of the body, and a disposable suction tip 3 installed at the end of the connecting tube 2.

[0039] The bubble visual detection module is used to automatically acquire images of the liquid inside the nozzle and identify bubbles. It includes an image sensor 4 and a light source 5.

[0040] Among them, image sensor 4 adopts a GC0308 SPI interface camera module. This module integrates a CMOS sensor, lens and driving circuit, and supports direct output of JPEG format images, which greatly reduces the processing burden of the main control microprocessor.

[0041] Light source 5 uses a side-emitting white LED bead, whose emission wavelength covers the visible light range.

[0042] The installation structure is as follows: Two opposing and symmetrical transparent optical observation windows 21 are set on the side wall of the connecting tube 2. These windows are sealed with highly transparent optical glass. A GC0308 camera module is fixedly installed on the side facing one observation window 21, with its lens directly opposite the window. The white LED is fixedly installed on the other observation window 21, with its optical axis substantially aligned with the camera's optical axis, forming a transmissive illumination path on opposite sides. When the connecting tube 2 and the suction head 27 are filled with liquid, the LED acts as a backlight, allowing the camera to capture images of the liquid column. Due to their different refractive indices, bubbles will appear as clearly defined shadows in the image.

[0043] The defoaming actuator module (direct-drive ultrasonic defoaming module) generates high-frequency vibrations to cause bubbles to coalesce and rise. It includes a vibration actuator 6 and a drive chip. The vibration actuator 6 employs a ring-shaped piezoelectric ceramic transducer (PZT), whose inner diameter matches the outer diameter of the connecting tube 2. This ring-shaped piezoelectric ceramic transducer is directly bonded to the middle of the outer wall of the connecting tube 2 using high-strength epoxy conductive adhesive, located above or below the optical observation window. This design eliminates traditional intermediate transmission components such as vibration rods and collars, achieving direct and efficient transmission of vibration energy. The drive chip uses a DRV8662 piezoelectric drive chip, which generates a high-voltage differential signal to drive the piezoelectric ceramic.

[0044] A small operation box 7 is provided on the surface of the sample gun body 1. The operation box 7 is equipped with a processing module, a prompt module, a user input unit and a power module.

[0045] The processing module uses an STM32G474RET6 microcontroller (i.e., the main control microcontroller (MCU)), integrating a DCMI interface for direct connection to the camera, and multiple I2C / SPI / USART interfaces for image processing and logic control. The SCK, MISO, MOSI, CS, and RST pins of the GC0308 SPI interface camera module are connected to the MCU's PA5, PA6, PA7, PB0, and PB1 pins respectively, for sending image information to the MCU. The INP and INN pins of the DRV8662 driver chip are connected to the MCU's complementary PWM output pins PA11 and PC13 via 100Ω resistors, while its EN and FAULT pins are connected to the MCU's PA15 and PB4 pins. An AP3602 LED driver chip is connected between the MCU and the LED. It is a boost-type constant current LED driver chip with integrated power MOSFET. It boosts the voltage through an external inductor and uses the chip's internal current detection circuit to provide a constant current to the LED. The EN / PWM pin is directly controlled by the MCU's PWM signal to achieve efficient dimming and adapt to liquids with different light transmittance.

[0046] The prompting module includes a display unit and a voice prompt unit. The display unit uses a 0.96-inch OLED display 8 driven by an SSD1306, integrated on the surface of the operation box 7, to display information such as detection results, compensation volume, and operation menus. The SDA and SCL pins of the OLED display 8 are connected to the PB7 and PB6 (I2C1) pins of the MCU. The voice prompt unit uses a SYN6288 Chinese speech synthesis module, connected to a miniature speaker (SPEEK), to broadcast prompt information. The RXD and TXD pins of the SYN6288 speech module are connected to the PA2 and PA3 pins of the MCU, respectively.

[0047] The user input unit includes three function buttons 9 (mode / detection button, execute / confirm button, cancel / return button) on the surface of the operation box 7, which are used to receive user commands and correspond to buttons K1, K2 and K3 in the circuit, respectively. The user can trigger the bubble detection process at any time by short-pressing the "detection button"; when the system prompts that debubbling is required, pressing the "execute button" will start the debubbling program; the "cancel button" is used to interrupt the current operation or return to the previous menu; and multiple setting buttons 10 on the surface of the operation box 7 are used to set parameters, which are represented by buttons K11, K12 and K13 in the circuit.

[0048] The power module includes a USB charging port 20 (located on the side wall of the control box 7), a TP4056A lithium battery charging management circuit, a rechargeable lithium battery (BAT), a MOSFET, a TPS63020 buck-boost converter (generating a stable 5V from the battery), and an AMS1117-3.3 regulator (stepping down the 5V to 3.3V). When an external USB power supply is plugged in, the MOSFET is turned on, and the external power supply provides power; when the external USB power supply is unplugged, the lithium battery provides power. A power switch 30 (corresponding to button K10 in the circuit) is connected in series on the output (VOUT) pin of the TPS63020 buck-boost converter to control the on / off state of the power supply circuit.

[0049] Example 2

[0050] This embodiment provides a bubble handling method applied to the above-mentioned pipette. This method realizes a closed loop of intelligent sensing, decision-making, and handling of bubbles, and specifically includes the following steps:

[0051] S0: Trigger detection. After the user completes sample aspiration, press the "Detection" button (button K1) on the pipette.

[0052] S1: Automatic image acquisition and bubble recognition. The MCU responds to button commands and executes subsequent acquisition, recognition, and calculation steps:

[0053] S1.1: Illuminate the LED light source on the opposite side to provide uniform backlighting for the observation window.

[0054] S1.2: Control the GC0308 camera module to take a JPEG image of the connecting tube and the liquid column inside the suction head.

[0055] S1.3: Perform image preprocessing (such as filtering and contrast enhancement).

[0056] S1.4: A threshold segmentation algorithm is used to identify regions in the image with gray values ​​below a set threshold as candidate bubble regions, and independent bubble regions are determined through connected component analysis.

[0057] S2: Bubble volume calculation. The MCU performs the following calculations:

[0058] S2.1: Dimensional Calibration. The known inner diameter D of the connecting pipe 10 is used as a reference. The system is calibrated at the factory: by taking an image of a blank pipe column with a known inner diameter, a conversion relationship between "image pixel distance" and "actual physical distance" is established to obtain the actual length K (unit: mm / pixel) corresponding to each pixel. This parameter is fixed in the MCU.

[0059] S2.2: For each individual bubble region, calculate its pixel area A_pixel in the image.

[0060] S2.3: Calculate the actual cross-sectional area of ​​the bubble A_real = A_pixel × K² based on the calibration coefficient K.

[0061] S2.4: Establish the bubble volume model. Since the bubble is inside the cylindrical connecting pipe, to simplify the calculation, its volume model can be approximated as a cylinder with a very small height. Assuming the bubble fills the entire pipe diameter, its volume V_bubble ≈ A_real × D (where D is the pipe diameter). A more accurate spherical cap model can also be used for calculation. The final total bubble volume V_bubble is the liquid volume lost due to the presence of the bubble.

[0062] S3: Threshold determination.

[0063] The processing module has a preset or user-configurable volume threshold V_threshold (set via a settings button). This threshold represents the upper limit of the bubble volume that can be ignored under specific experimental precision requirements. The processing module compares the calculated bubble volume V_bubble with the threshold V_threshold:

[0064] If V_bubble < V_threshold: the influence of bubbles is considered negligible, and the process jumps directly to S7: complete sample preparation. The prompt module displays "Ready" or "Volume meets requirements," and the subsequent debubbling and compensation processes are not initiated.

[0065] If V_bubble ≥ V_threshold: the bubble is deemed to have a significant impact and needs to be processed; the process continues with subsequent steps.

[0066] S4: Information Prompt. Based on the calculation results, the MCU will perform at least one of the following prompt operations:

[0067] S4.1: Display on the OLED screen: "Bubble detected, volume: X.XX μl".

[0068] S4.2: The speech synthesis module announces: "Bubble detected, please prepare to remove bubbles" or directly announces the volume value.

[0069] S5: Debubbling Execution. Following the prompts, the user presses the "Execute" button (button K2). The MCU responds to this command, controlling the DRV8662 driver chip to drive the piezoelectric ceramic bonded to the connecting tube to generate high-frequency vibrations (e.g., 40kHz) for a set time (e.g., 2 seconds), causing bubbles to coalesce, rise, and be discharged from the liquid surface.

[0070] S6: Volume Compensation Guidance. After debubbling, the MCU displays "Please aspirate X.XX μl" on the OLED screen and simultaneously announces this information via voice. X.XX μl is the V_bubble value calculated in step S2. After seeing / hearing the prompt, the user manually rotates the volume adjustment knob on the pipette to reduce the set value by X.XX μl, then immerses the pipette tip back into the original sample solution to trigger the aspiration operation. This step precisely compensates for the liquid lost due to air bubble removal, ensuring that the final liquid volume in the pipette tip equals the user's initial target volume.

[0071] S7: Sample preparation complete. After compensation is complete, the system will display "Ready". The user can then add the precise volume of liquid to the target container.

[0072] In summary, this invention, through the integrated hardware architecture described in Embodiment 1 and the intelligent workflow defined in Embodiment 2, together constitutes a complete bubble detection and processing solution. Its core lies in the deep integration of machine vision-based automatic bubble detection and precise quantification technology, efficient direct-drive vibration defoaming technology, and guided volume compensation prompting technology. This solution creatively transforms the physical existence of bubbles into quantifiable volume data, using this data to drive subsequent defoaming and compensation operations. Ultimately, with simple operator cooperation, a closed-loop precision control chain from "perception" to "correction" is formed, thereby fundamentally solving the long-standing technical problem of volume errors caused by bubbles during sample addition, significantly improving the reliability, automation, and user experience of sample addition operations.

Claims

1. A bubble detection and prompting sample adding gun, comprising a sample adding gun body and a connecting pipe, a piston driving mechanism is arranged in the sample adding gun body, the connecting pipe is arranged at the bottom of the sample adding gun body and is used for mounting a disposable suction head; characterized in that, Also includes: A bubble visual detection module is used to acquire images of the liquid inside the connecting tube and the suction head; The processing module, connected to the bubble visual detection module, is used to identify bubbles and calculate bubble volume based on the image; The prompting module, connected to the processing module, is used to output compensation prompt information related to the volume of the bubble; A defoaming execution module, connected to the processing module, is used to generate vibration to remove bubbles according to the instructions of the processing module; The user input module is connected to the processing module. The user input module includes at least one function key for receiving user operation instructions to trigger the operation of the bubble visual detection module and / or the debubbling execution module.

2. The sample dispenser according to claim 1, characterized in that, The bubble visual detection module includes an image sensor and a light source arranged on opposite sides. The side wall of the connecting tube is provided with an observation window for light to pass through. The image sensor and the light source are respectively arranged on both sides of the observation window to form a transmissive illumination light path. The image sensor is a GC0308 type SPI interface camera module.

3. The sample dispenser according to claim 2, characterized in that, The defoaming execution module includes a piezoelectric ceramic transducer, which is directly fixed to the outer wall of the connecting pipe.

4. The sample dispenser according to claim 3, characterized in that, It also includes a piezoelectric drive chip, whose differential output terminal is connected to the piezoelectric ceramic transducer, and whose differential input terminal is used to receive a pair of complementary PWM signals from the processing module.

5. The sample dispenser according to claim 1, characterized in that, The prompting module includes at least one of a display submodule and a voice broadcast submodule; the display submodule is an OLED display screen, and the voice broadcast submodule includes a SYN6288 voice synthesis chip and a speaker.

6. The sample dispenser for bubble detection and indication according to claim 1, characterized in that, The user input module includes three function buttons, which are defined as the detection button, the execution button, and the cancel button.

7. A method for treating air bubbles in a sample dispenser according to any one of claims 1-6, characterized in that, Includes the following steps: In response to the user's first operation on the function key, the image acquisition step is triggered; Image acquisition steps: After the sample is drawn up by the pipette, images of the liquid inside the connecting tube and pipette tip are acquired through the bubble visual detection module; Bubble recognition and volume calculation steps: The processing module recognizes bubbles based on the image and calculates the volume of the bubbles based on the known inner diameter parameters of the connecting pipe; Prompt Steps: The prompt module outputs compensation prompt information related to the calculated bubble volume; In response to a second operation by the user on the function key, a debubbling step is triggered. Defoaming step: The defoaming execution module is activated to generate vibration to remove air bubbles; Compensation guidance steps: Based on the compensation prompt information, guide the operator to compensate for the liquid volume lost due to bubble removal.

8. The bubble treatment method according to claim 7, characterized in that, The bubble identification and volume calculation steps specifically include: The acquired images are preprocessed and thresholded to identify bubble regions; Calculate the pixel area occupied by the bubble region in the image; Based on the pre-calibrated conversion relationship between the known inner diameter of the connecting pipe and the image pixels, the pixel area is converted into the actual cross-sectional area; The volume of the bubble is calculated using a geometric model based on the actual cross-sectional area and the known inner diameter of the connecting pipe.

9. The bubble treatment method according to claim 7, characterized in that, The compensation guidance step specifically involves displaying and / or broadcasting the volume value to be replenished on the screen, whereby the volume value to be replenished is equal to the calculated bubble volume, to guide the user to manually adjust the dispensing gun settings and replenish the corresponding volume of liquid.

10. The bubble treatment method according to claim 7, characterized in that, Between the bubble identification and volume calculation step and the prompting step, the following is also included: Threshold determination steps: Compare the calculated bubble volume with a preset or user-defined volume threshold; The subsequent prompting step, debubbling step, and compensation guidance step are only executed when the bubble volume is greater than or equal to the volume threshold. If the bubble volume is less than the volume threshold, the process ends and a "ready" message is displayed.

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