Intelligent micro liquid control system and method

Abstract

The invention discloses an intelligent micro liquid control system and method, and belongs to the field of biological research systems. According to the system, a screw is fixedly arranged on one transverse side of a machine body, a round hole is formed in the machine body downwards in the longitudinal direction, and a swivel bolt penetrates through the round hole to be bolted with an inverted microscope; the machine body is longitudinally bolted with the longitudinal rear wall of the precise stepping motor through a screw; one transverse side of the lifting displacement table is in bolted connection with a precise stepping motor, and the precise stepping motor controls the lifting displacement table to move in the longitudinal direction; a round hole is longitudinally and fixedly formed in the center of the lifting translation table, and threads are arranged in the round hole; luer lock joints are inserted into the two longitudinal sides of the round hole of the lifting translation table; the upper end of the Luer lock connector is in compression joint with the longitudinal upper side of the infusion tube, the other end of the infusion tube is connected with the precise micropump, the precise micropump is arranged in the machine body, and the lower end of the Luer lock connector is in screwed connection with the longitudinal lower side of the microinjection needle. The problems that existing manual operation is low in efficiency, poor in precision and insufficient in repeatability are solved.

Description

Technical Field

[0001] The present invention belongs to the technical field of biological research systems, and particularly relates to an intelligent micro liquid manipulation system and method. Background Art

[0002] With the development of technology, microfluidic technology has been widely applied in the fields of biomedicine, chemical analysis, drug research and development, etc. Traditional liquid manipulation methods rely on manual operation, which have disadvantages such as inaccurate operation, low efficiency, and being easily affected by human factors. Especially in the manipulation of micro liquids, accuracy and operation stability are particularly important.

[0003] However, in this field, the existing technical means are not well developed. Due to the unique requirements of biological precision manipulation, many pump products on the market cannot meet their application needs, or can meet the needs but cannot be matched with precision cell manipulation equipment. At the same time, the existing automated injection systems still have great limitations in terms of flexibility, adaptability, and operation simplicity. Summary of the Invention

[0004] The purpose of the present invention is to provide an intelligent micro liquid manipulation system and method, which solves the problems of low efficiency, poor accuracy, and insufficient repeatability of existing manual operations.

[0005] The present invention adopts the following technical solutions: An intelligent micro liquid manipulation system, the system includes:

[0006] A fuselage, a screw is fixedly arranged on one lateral side of the fuselage horizontally, and a round hole is arranged vertically downward on the fuselage. A rotating bolt passes through this round hole and is bolted to an inverted microscope; the fuselage and the longitudinal rear wall of a precision stepper motor are longitudinally bolted through screws.

[0007] A lifting displacement stage, the fuselage is located above the lifting displacement stage; one lateral side of the lifting displacement stage is bolted to the precision stepper motor, and the precision stepper motor controls the lifting displacement stage to move longitudinally; a round hole is fixedly arranged longitudinally at the center of the lifting translation stage, and a thread is arranged inside the round hole.

[0008] A Luer lock connector, the Luer lock connector is inserted into both longitudinal sides of the round hole of the lifting translation stage.

[0009] An infusion tube and a micro injection needle, the upper end of the Luer lock connector is press-connected to the upper side of the infusion tube longitudinally, the other end of the infusion tube is connected to a precision micro pump, the precision micro pump is placed in the fuselage, and the lower end of the Luer lock connector is screwed to the lower side of the micro injection needle longitudinally.

[0010] Preferably, both the fuselage and the rotating bolt are made of aluminum alloy material and are both subjected to anti-oxidation treatment.

[0011] Preferably, the lifting translation stage is made of transparent acrylic material.

[0012] Preferably, the Luer lock connector is made of transparent plastic material.

[0013] Preferably, the infusion tube is made of flexible material.

[0014] Preferably, the inner diameter of the microinjection needle is 30 μm and 300 μm.

[0015] Preferably, the 30-μm microinjection needle is made of quartz material and plastic material, and the 300-μm microinjection needle is made of metal material and plastic material.

[0016] The present invention also provides another technical solution, a control method for an intelligent micro-liquid control system, comprising the following steps:

[0017] Step 1: After power-on, the intelligent micro-liquid control system automatically initializes each hardware component, communicates through the serial communication interface, obtains the position data of the precision stepper motor and the inverted microscope automatic translation stage, and performs preliminary calibration through the position deviation correction algorithm. Calculate the deviation between the current positions of the precision stepper motor and the inverted microscope automatic translation stage and the preset target position in real time, adjust the position of the precision stepper motor, and after calibration is completed, control the precision stepper motor to reset.

[0018] Step 2: After calibration, identify the real-time acquisition captured by the inverted microscope through the image processing and target detection algorithm, and mark the identified target area with curves of different colors.

[0019] Step 3: After the target area is identified, the operator can manually or automatically select a suitable injection point.

[0020] Step 4: Control the movement of the inverted microscope automatic translation stage through the automatic translation control algorithm, and move the target site directly below the microinjection needle.

[0021] Step 5: After the microinjection needle is aligned with the target point, drive the precision stepper motor to carry the lifting and translation stage down to a suitable height. Through the image feedback and real-time adjustment algorithm, evaluate the distance between the microinjection needle and the target sample based on the brightness and size of the microinjection needle in the real-time image feedback. If the appropriate height is not reached, continue to drive the precision stepper motor to descend.

[0022] Step 6: When the microinjection needle is aligned with the target injection point and the lifting and translation stage carries the microinjection needle to the specified appropriate height, the intelligent micro-liquid control system stops moving the precision stepper motor and starts the precision micropump to precisely control the target sample. The precision micropump can be controlled according to the algorithm, and timed, constant-speed, or quantitative injection or aspiration can be achieved according to experimental requirements.

[0023] Step 7: After the operation is completed, the intelligent micro-liquid control system will drive the precision stepper motor to rise and return to its original position, and at the same time, a pop-up window on the operation interface will prompt that the operation is completed.

[0024] The beneficial effects of the present invention are as follows: (1) The present invention uses the method of the fuselage and the rotating bolt to be threadedly connected to the condenser screw on the inverted microscope, and the inner diameter of the circular hole of the fuselage can also be changed according to the outer diameter of the rotating bolt. The present invention uses a precision stepper motor, which has the characteristics of being sturdy, small and precise, and can achieve micron-level stepping control, so as to achieve precise control when the intelligent micro-liquid control system moves longitudinally.

[0025] (2) The present invention connects the lifting and translation stage with a precision stepper motor, so as to drive the Luer lock connector and the micro-injection needle and infusion tube installed on the Luer lock connector to move precisely longitudinally. This makes the replacement of the infusion tube and the micro-injection needle very simple and fast, improving the use efficiency. The present invention uses an intelligent algorithm for control, and this algorithm can effectively ensure the accuracy, accuracy, repeatability and high efficiency of the experiment. Description of the Drawings

[0026] Figure 1 It is a schematic structural diagram of the intelligent micro-liquid control system of this application;

[0027] Figure 2 It is a flow chart of the control algorithm of the intelligent micro-liquid control system of this application.

[0028] Among them, 1. Fuselage; 2. Rotating bolt; 3. Luer lock connector; 4. Infusion tube; 5. Lifting displacement stage; 6. Micro-injection needle; 7. Screw; 8. Precision stepper motor. Specific Embodiments

[0029] Next, the technical solutions in the embodiments of this application will be described clearly and completely. Obviously, the described embodiments are only a part of the embodiments of this application, rather than all the embodiments. Based on the embodiments in this application, all other embodiments obtained by those of ordinary skill in the art without creative work shall fall within the protection scope of this application.

[0030] As Figure 1 shown, this application proposes an intelligent micro-liquid control system, which includes: a fuselage 1, a rotating bolt 2, a precision stepper motor 8, a screw 7, a lifting displacement stage 5, a Luer lock connector 3, an infusion tube 4, a micro-injection needle 6, a precision micropump, a control card for controlling the motor 8 and the precision micropump, a gas pipeline, a liquid pipeline, and a computer.

[0031] A screw 7 is fixedly arranged on one side of the fuselage 1 in the horizontal direction, and a circular hole is arranged longitudinally on the fuselage 1. The rotating bolt 2 passes through this circular hole and is bolted to the inverted microscope.

[0032] The inner diameter of the circular hole in the longitudinal direction of the fuselage 1 and the outer diameter of the rotating bolt 2 can be changed according to the size of the inverted microscope, so as to adapt to different models of inverted microscopes.

[0033] Both the fuselage 1 and the rotating bolt 2 are made of aluminum alloy material and are subjected to anti-oxidation treatment, with the characteristics of high strength, not easy to deform, high temperature resistance and corrosion resistance.

[0034] Precision stepper motor 8, the longitudinal rear wall of the precision stepper motor 8 is bolted to the fuselage 1 longitudinally through screws.

[0035] Lifting displacement table 5, one side of the lifting displacement table 5 in the transverse direction is bolted to the precision stepper motor 8, and it can move longitudinally with the precision stepper motor 8. There is a round hole on the other side of the lifting and translation table 5 in the longitudinal direction, and there is a thread in the hole.

[0036] The lifting and translation table 5 is made of transparent acrylic material, with high light transmittance and relatively high strength.

[0037] Luer lock connector 3, the Luer lock connector 3 is inserted into the longitudinal two sides of the round hole of the lifting and translation table 5 and is tightly locked through the thread in the round hole. The Luer lock connector 3 is made of transparent plastic material, with the characteristics of temperature and pressure resistance and light transmission.

[0038] Infusion tube 4 and micro-injection needle 6, the upper end of the Luer lock connector 3 is press-connected to the longitudinal upper side of the infusion tube 4, the other end of the infusion tube 4 is connected to a precision micropump, and the lower end of the Luer lock connector 3 is screwed to the longitudinal lower side of the micro-injection needle 6.

[0039] In some embodiments, the infusion tube 4 is made of flexible material, with the characteristics of being bendable, temperature and pressure resistant, with an outer diameter of 1.52 mm and an inner diameter of 0.51 mm.

[0040] The inner diameter size of the micro-injection needle 6 has two types: 30 μm and 300 μm. The micro-injection needle 6 with a diameter of 30 μm is made of quartz material and plastic material, and the micro-injection needle 6 with a diameter of 300 μm is made of metal material and plastic material, so as to take into account the characteristics of miniaturization and firmness.

[0041] As Figure 2 shown, the control method process of an intelligent micro-liquid control system of the present application is as follows:

[0042] Step 1: Initialization and calibration of hardware components

[0043] Assemble the fuselage 1 and the rotating bolt 2 of the intelligent micro-liquid control system on the inverted biological microscope platform, adjust the lifting and translation table 5 to be horizontal, and install the micro-injection needle 6 and the infusion tube 4.

[0044] After startup, the intelligent micro - liquid manipulation system will automatically initialize each hardware component. The intelligent micro - liquid manipulation system establishes a communication connection with the precision stepper motor 8 through a serial communication interface, sends specific query instructions, and obtains the current position data of the precision stepper motor 8. At the same time, the position information of the inverted microscope automatic translation stage is obtained in the same way.

[0045] A preliminary calibration is carried out using a position deviation correction algorithm. This algorithm calculates the deviation value between the current position and the preset target position in real - time according to the preset standard position parameters. If the deviation value exceeds the allowable range, the system will send corresponding pulse signals to the precision stepper motor 8 according to the direction and magnitude of the deviation, adjust its rotation steps and direction, so as to accurately adjust the position of the precision stepper motor 8. When the calibration is completed, the system sends a reset instruction to control the precision stepper motor 8 to return to the initial set reset position.

[0046] The intelligent micro - liquid manipulation system observes and focuses on the zebrafish placed on the stage of the inverted microscope. After focusing, image data of the zebrafish is obtained through a high - resolution imaging device.

[0047] Step 2: Image Processing and Target Detection

[0048] After calibration, the intelligent micro - liquid manipulation system will call the image processing and target detection algorithm to analyze and process the real - time images captured by the inverted microscope. The system will identify the overall contour and internal structure of the zebrafish through the image processing and target detection algorithm for the real - time acquisition captured by the inverted microscope. Through the image segmentation algorithm, the system accurately divides each anatomical part of the zebrafish, such as the head, heart, abdomen, and blood vessels, etc., and marks the corresponding areas on the image. The target areas are marked with curves of different colors, providing intuitive and accurate references for researchers.

[0049] Step 3: Injection Point Selection

[0050] After the target area is identified, the operator can manually or automatically select a suitable injection point.

[0051] Step 4: Automatic Translation Control

[0052] After determining the injection point, the intelligent micro - liquid manipulation system starts the automatic translation control algorithm to control the movement of the inverted microscope automatic translation stage. The intelligent micro - liquid manipulation system calculates the distance and direction that the automatic translation stage needs to move according to the relative position relationship between the current target site and the micro - injection needle 6. By sending precise control pulses to the drive motor of the automatic translation stage, the precise movement of the automatic translation stage is realized, and the target site is accurately moved directly below the micro - injection needle 6.

[0053] Step 5: Height Adjustment and Image Feedback

[0054] After the micro-injection needle 6 is aligned with the target point, the intelligent micro-liquid control system drives the precision stepper motor 8 to carry the lifting and translation stage 5 downward. The intelligent micro-liquid control system analyzes the real-time acquired images by using image feedback and real-time adjustment algorithms. Through image recognition technology, the brightness and size information of the micro-injection needle 6 in the image are extracted.

[0055] According to the pre-established mapping relationship model of brightness, size and distance, the distance between the micro-injection needle 6 and the target sample is evaluated. If the appropriate height is not reached, the intelligent micro-liquid control system will continue to send a driving signal to the precision stepper motor 8 to control it to further descend until the appropriate height is reached.

[0056] Step 6, Precise Manipulation and Parameter Control

[0057] When the micro-injection needle 6 is aligned with the target injection point and the lifting and translation stage 5 carries the micro-injection needle 6 to the specified appropriate height, the intelligent micro-liquid control system stops moving the precision stepper motor 8 and starts the precision micro-pump to precisely manipulate the target sample. According to the algorithm, the precision micro-pump can be controlled to achieve timed, fixed-speed or quantitative injection or aspiration according to experimental requirements. The researcher can select a suitable injection point on the screen and displace the translation stage of the inverted microscope to move the target injection point directly below the micro-injection needle 6. Subsequently, the algorithm manipulates the precision stepper motor 8 to drive the lifting and translation stage 5 to move longitudinally to the appropriate height and drive the pressure for injection or aspiration.

[0058] Step 7, Operation Completion and Home Position Prompt

[0059] When the manipulation work is completed, the intelligent micro-liquid control system drives the precision stepper motor 8 to rise to the home position. At the same time, the intelligent micro-liquid control system pops up a prompt window on the operation interface to inform the operator that the operation has been completed.

[0060] The use of the intelligent micro-liquid control system of the present application can further improve the accuracy and efficiency of the experiment. The whole process is highly automated, reducing human intervention, realizing full-process visualization, data traceability, ensuring data accuracy and experiment repeatability.

[0061] Although the content of the present application has been introduced in detail through the above preferred embodiments, it should be recognized that the above description should not be considered as a limitation of the present application. After those skilled in the art have read the above content, various modifications and substitutions to the present application will be obvious. Therefore, the protection scope of the present application should be defined by the appended claims.

Claims

1. An intelligent micro-liquid manipulation system, characterized in that: The system includes: A body (1), a screw (7) is fixedly arranged on one lateral side of the body (1), a circular hole is arranged longitudinally downwardly on the body (1), and a rotating bolt (2) passes through the circular hole and is bolted to the inverted microscope; the body (1) is bolted to the longitudinal rear wall of the precision stepping motor (8) longitudinally by screws; A lifting and displacement platform (5), wherein the body (1) is located above the lifting and displacement platform (5); a lateral side of the lifting and displacement platform (5) is bolted to the precision stepping motor (8), and the precision stepping motor (8) controls the lifting and displacement platform (5) to move in the longitudinal direction; a circular hole is fixedly provided in the longitudinal direction at the center of the lifting and displacement platform (5), and a thread is provided in the circular hole; Luer lock connector (3), the Luer lock connector (3) is inserted into the longitudinal sides of the circular hole of the lifting and translation platform (5); An infusion tube (4) and a microinjection needle (6), wherein the upper end of the Luer lock connector (3) is crimped to the longitudinal upper side of the infusion tube (4), the other end of the infusion tube (4) is connected to a precision micropump, the precision micropump is placed in the body (1), and the lower end of the Luer lock connector (3) is screwed to the longitudinal lower side of the microinjection needle (6).

2. The intelligent micro-liquid manipulation system according to claim 1, characterized in that: The body (1) and the rotating bolt (2) are both made of aluminum alloy and are both subjected to anti-oxidation treatment.

3. The intelligent micro-liquid manipulation system according to claim 1, characterized in that: The lifting and translation platform (5) is made of a transparent acrylic material.

4. The intelligent micro-liquid manipulation system according to claim 1, characterized in that: The Luer lock connector (3) is made of a transparent plastic material.

5. The intelligent micro-liquid manipulation system according to claim 1, characterized in that: The infusion tube (4) is made of a flexible material.

6. The intelligent micro-liquid manipulation system according to claim 5, characterized in that: The inner diameter of the microinjection needle (6) is 30 μm and 300 μm.

7. The intelligent micro-liquid manipulation system according to claim 6, characterized in that: The 30 μm microinjection needle (6) is made of quartz material and plastic material, and the 300 μm microinjection needle (6) is made of metal material and plastic material.

8. A control method using the intelligent micro-liquid manipulation system according to any one of claims 1 to 7, characterized in that: The steps include: Step 1: After powering on, the intelligent micro-liquid manipulation system automatically initializes each hardware component, communicates through a serial communication interface, obtains position data of the precision stepper motor (8) and the automatic translation stage of the inverted microscope, performs preliminary calibration through a position deviation correction algorithm, calculates in real time the deviation between the current position of the precision stepper motor (8) and the automatic translation stage of the inverted microscope and the preset target position, adjusts the position of the precision stepper motor (8), and after the calibration is completed, controls the precision stepper motor (8) to reset; Step 2: After calibration, the real-time acquisition captured by the inverted microscope is identified through image processing and target detection algorithms, and the identified target area is divided and marked with curves of different colors; Step 3: After the target area is identified, the operator can select the appropriate injection point manually or automatically; Step 4, controlling the automatic translation stage of the inverted microscope to move by an automatic translation control algorithm to move the target site to the position directly below the microinjection needle (6); Step 5, after the microinjection needle (6) is aligned with the target point, the precision stepper motor (8) is driven to carry the lifting and translation stage (5) to move downward to a suitable height, and the distance between the microinjection needle (6) and the target sample is evaluated according to the brightness and size of the microinjection needle (6) in the real-time image feedback through image feedback and real-time adjustment algorithm. If the suitable height is not reached, the precision stepper motor (8) is continued to be driven downward; Step 6: When the microinjection needle (6) is aligned with the target injection point and the lifting and translation stage (5) carries the microinjection needle (8) to a designated appropriate height, the intelligent micro-liquid manipulation system stops moving the precision stepping motor (8) and starts the precision micropump to precisely manipulate the target sample. The precision micropump can be controlled according to the algorithm to achieve timed, fixed-speed or quantitative injection or aspiration according to experimental requirements; Step 7: After the manipulation is completed, the intelligent micro-liquid manipulation system will drive the precision stepping motor (8) to rise and return to its original position, and a pop-up window will appear on the operation interface to prompt that the operation is completed.

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