Processing unit for detecting experimental animal behaviors, experimental operation device and interactive terminal

By designing an experimental system based on stem cell transplantation, and using image and electromyography signal acquisition technology, the problem of artificial subjective deviation in the judgment of experimental animals is solved, and data accuracy and reliability of experimental results are improved.

CN119523674AActive Publication Date: 2025-02-28BEIJING EASENG MEDICAL SCI CO LTD
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Patent Information

Application Number
CN202411584923.6
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2023-03-07
Publication Date
2025-02-28
Estimated Expiration
2043-03-07

AI Technical Summary

Technical Problem

In the prior art, the behavioral judgment of experimental animals depends on manual planning and equipment planning, resulting in naked-eye observation being affected by environmental, time and memory bias, resulting in cognitive bias and evaluation errors.

Method used

Design an experimental system based on stem cell transplantation, including the behavioral detection unit and processing unit of animal experimental subjects. Through image information acquisition and electromyography signal acquisition, the collection and analysis of experimental animals' movement, sensory and balance data are realized, and the error caused by manual judgment is reduced.

Benefits of technology

Through automated data acquisition and analysis, the subjective deviation of manual judgment is reduced, the accuracy and reliability of experimental data are improved, and the accuracy of experimental results is ensured.

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Patent Text Reader

Abstract

The invention relates to a processing unit for detecting experimental animal behaviors, an experimental operation device and an interaction terminal, the processing unit is used for detecting the experimental animal behaviors, and the processing unit can control a mechanical arm and an image acquisition unit; the processing unit is configured to control the mechanical arm to generate an operation mode corresponding to a specified activity area to grab a specified part of the experimental animal under the condition that the experimental animal enters the specified activity area, and judge the behavior and / or behavior track of the experimental animal based on the image data, sent by the image acquisition unit, of the experimental animal; and the processing unit controls the image acquisition unit to perform close-shot image acquisition or long-shot image acquisition on the experimental animal corresponding to the specified activity area, and in response to selection of an experimenter on a two-dimensional image, controls the image acquisition unit to generate images which are displayed on the interactive terminal in parallel in two-dimensional and three-dimensional modes. Observation area prompts can be provided for experimenters, and disorder of observation positions is avoided.
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Description

[0001] The original basis of this divisional application is a Chinese patent application with application number (202310211940.4), application date 2023.03.07, and invention name “An experimental system based on stem cell transplantation”. Technical Field

[0002] The present invention relates to the field of biotechnology, and in particular to a processing unit, an experimental operation device and an interactive terminal for detecting the behavior of experimental animals. Background Art

[0003] Human hematopoietic stem cells come from the mesothelial cells of the yolk sac in the embryonic period and are the most unique somatic cell group in the human body. Like APSC pluripotent cells, they are a type of primitive cells with the potential for self-replication and multidirectional differentiation. They are also the most basic driving force for maintaining life. Multifunctional activated cell anti-aging is to use tissue cells collected from the body, separate and culture them in the laboratory, and then inject the proliferated stem cells back into the human body. Through the self-targeting function of multifunctional activated cells, they can accurately reach the corresponding damaged organs and tissues, so as to achieve the purpose of repairing aging and diseased cells and rebuilding normal functioning cells and tissues.

[0004] Stem cell transplantation types are at least divided into bone marrow stem cell transplantation, peripheral blood hematopoietic stem cell transplantation and umbilical cord blood hematopoietic stem cell transplantation. Different drugs used for diseases that require stem cell transplantation need to be applied to disease model experimental animals and experimental animals after stem cell transplantation during the animal pharmacology testing stage. Based on the behavioral performance of experimental animals at different stages, experimenters can confirm the efficacy of the drug, among which the behavioral performance of experimental animals at different stages is crucial for experimenters to judge the efficacy of the drug.

[0005] In the prior art, the behavior judgment of experimental animals mainly relies on manual planning and equipment planning. Manual planning is: according to different behavioral experimental requirements, the experimental animals are manually operated, such as lifting the tail and driving, and the score evaluation of whether the behavior of the experimental animals is normal or not is based on subjective observation.

[0006] Equipment planning is the behavior development of experimental animals fixed by experimental personnel based on experimental equipment, and the error caused by naked eye observation of experimental animal behavior is reduced by unifying the behavior of experimental animals. The Chinese patent with publication number CN113314011B discloses a multifunctional experimental device for small animal neurobehavioral assessment, including: an experimental cavity shell, a shock-absorbing mobile mechanism is installed at its lower end, a breathable net for ventilation is installed inside the inner cavity shell, and an additional experimental platform mechanism placed in the inner cavity shell is provided on the inner side of the breathable net, and the additional experimental platform mechanism includes a connecting rod, a test bench and a fixing bolt, a fixing bolt is fixed on the inner side of the connecting rod, and an excrement leakage net installed in the experimental cavity shell is provided on the lower side of the inner cavity shell. The equipment limits the travel route of experimental animals, reduces the impact of vibration on the internal environment of the device being tested, and increases the accuracy of the verification results of the control variable method.

[0007] Compared with merely planning the behavior of experimental animals, the Chinese patent with publication number CN114420297A provides a neurological function assessment and training system for experimental rat models of central nervous system diseases, which belongs to the field of medical tracking and evaluation technology. The system includes three major parts: an assessment system, a training system, and a scoring system; the assessment system includes: three major aspects of motor function, sensory function, and brain cognitive function; the training system includes: motor function training, sensory function training, and brain cognitive function training; the scoring system designs a scoring table based on reliability and validity evaluation, and uses the scoring table to calculate each score and the total score. The feature of the present invention is that a more comprehensive assessment can be made for the functional disorders of rat models of central nervous system diseases. On the one hand, the evaluation items and design of the system are not suitable for monitoring the behavior of experimental animals before and after stem cell transplantation; on the other hand, the system only limits animal behavior, and quantifies animal behavior to various numerical values ​​to reduce data errors caused by naked eye observation.

[0008] However, in the actual experimental process, the naked eye observation of the experimenters will be affected by the environment, observation time and memory bias, which will cause cognitive bias on the different behaviors of different experimental animals, thereby leading to evaluation errors of animal behavior scores. Based on this, the present invention provides an experimental system based on stem cell transplantation.

[0009] In addition, on the one hand, there are differences in understanding among those skilled in the art; on the other hand, the applicant studied a large number of documents and patents when making the present invention, but due to space limitations, not all details and contents are listed in detail. However, this does not mean that the present invention does not have the characteristics of these prior arts. On the contrary, the present invention already has all the characteristics of the prior art, and the applicant reserves the right to add relevant prior art to the background technology. Summary of the invention

[0010] The experimental animals need to undergo the establishment of a cerebral hemorrhage model and behavioral analysis after transplantation before and after the experiment. Behavioral analysis at different stages has an important impact on both horizontal and vertical data comparisons. In the horizontal comparison process, the behavior of experimental animals in the normal stage is used as a benchmark, and the data at a certain stage can be used to determine whether the experimental operation at that stage is successful, for example, whether the modeling of experimental animals is successful. In the longitudinal comparison process, comparing the behaviors at different stages can be used to confirm the effectiveness of experimental operations or administered substances. Therefore, the collection of animal behavior data in animal behavior analysis has an important impact on the correctness of the results.

[0011] In the prior art, animal behavior data is often observed with the naked eye and converted into evaluation scores based on the subjective judgment of the experimenter. In the two processes of naked eye observation and subjective judgment of the brain, due to the subjective bias of the human body, the recorded data is very likely to have large errors. With the requirements for precise calibration of experimental data, the planning equipment for animal behavior has gradually increased, but the corresponding animal behavior data collection still depends on the experimenter.

[0012] In view of the above problems, the present invention provides an experimental system based on stem cell transplantation. The system may include an animal experimental subject behavior detection unit and a processing unit, wherein, based on the behavioral analysis requirements of the cerebral hemorrhage animal model before the experiment and the stem cell transplantation animal model after the experiment, the animal experimental subject behavior detection unit is provided with at least two detection units for image information acquisition and electromyographic signal acquisition, and based on the setting of at least two detection units, the motor experiment data, sensory experiment data and balance bar experiment data of the animal model can be acquired, and the data acquisition of mice with different treatments in the same environment can be analyzed based on the processing unit, so that the evaluation criteria of the relevant animal experiments can avoid the problem of analysis errors caused by manual judgment.

[0013] The experimental system includes an experimental operation unit, a data acquisition unit and a processing unit.

[0014] The data acquisition unit includes an image acquisition component and an electromyographic signal acquisition component.

[0015] The experimental operation unit comprises a motion base plate for guiding the experimental animal to produce detection behavior, a movable mechanical arm, an auricle reflex detection component, a sound reflex detection component and a corneal reflex detection component.

[0016] The mechanical arm can lift some limbs of the experimental animal and perform operations such as turning, moving or suspending the experimental animal. The experimental operation unit can place the experimental animal at the positioned position based on the positioning sent by the processing unit.

[0017] The first direction is the direction in which the mouse moves. The second direction is a direction perpendicular to the first direction on the plane of the moving base. The moving base is provided with at least one moving column along the second direction, each moving column can hold an experimental animal and enable the experimental animal to move along the first direction.

[0018] The moving base plate is provided with at least four moving areas in the first direction, wherein:

[0019] The first activity area is the experimental animal extremity movement sensation detection area. The second activity area is the experimental animal reflex detection area. The third activity area is the experimental animal planar movement detection area. The fourth activity area is the experimental animal balance detection area. The motion base plate is provided with at least two motion columns along the second direction, and each motion column is provided with a mechanical arm, an auricle reflection detection component, a corneal reflection detection component and a sound reflection detection component at the same position along the first direction. The dependent processing unit coordinates the animal behavior planning and the animal behavior collection, so that the control variables of the animal neurological behavior detection remain unique.

[0020] The first direction is radial, i.e. the direction in which a single experimental animal moves. The second direction is lateral, i.e. the direction in which multiple experimental animals are tested in parallel.

[0021] Advantages of this technical solution: In the prior art, the study of the neurological activity behavior of experimental animals is mainly based on the method of artificially inducing experimental animals, and the test method for experimental animals is carried out according to subjective conditions. For experimental animals, especially those that have undergone physiological changes, each behavioral test will have a physiological or psychological impact on them. The present invention plans the order and types of test items for experimental animals based on experimental animals after stem cell transplantation, and reduces the interference between tests by reducing the impact of each test on the experimental animals.

[0022] Each movement column of the movement base is provided with a mechanical arm in the first activity area, and the mechanical arm can at least grasp the tail, head or forelimb of the experimental animal.

[0023] Each movement column of the movement base plate is sequentially provided with an auricle reflection detection component, a corneal reflection detection component and a sound reflection detection component in the second activity area. The auricle reflection detection component can touch the external auditory canal of the experimental animal when the experimental animal enters the detection range. The corneal reflection detection component can touch the cornea of ​​the experimental animal when the experimental animal enters the detection range. The sound reflection detection component can emit a preset audio when the experimental animal enters the detection range.

[0024] Each moving column of the moving base is provided with an image acquisition unit at the end of the fourth activity area. The image acquisition unit is capable of performing image acquisition of the behavior of the experimental animals in the moving column. An image acquisition unit capable of performing image acquisition of the experimental animals in part or all of the area of ​​the moving base is provided at the end of the moving base, wherein the data acquisition type of the image acquisition unit includes the behavior of the experimental animals and the travel route of the experimental animals, and the data is used to provide a basis for the processing unit to evaluate the behavior of the experimental animals. Preferably, each moving column of the moving base is provided with a corresponding image acquisition unit for performing image acquisition of the entire area of ​​the moving column.

[0025] Mice, rats and rabbits are the most commonly used animal species for stem cell transplantation research in existing technologies. Mice and rats are small in size, and rabbits have long hair. When conducting animal experiments, the tiny reactions of their extremities cannot be observed by the naked eye. Even if they can be mechanically recorded, the final experimental data statistics still require human eyes to see changes in the extremities of the experimental animals.

[0026] The system adopts an image recording method to observe the limb changes of experimental animals. After the image is recorded, the system can provide the experimenter with a two-dimensional image of the experimental animal in response to the experimenter's operating instructions on the interactive terminal, and generate an image displayed in parallel on the interactive terminal in two-dimensional and three-dimensional ways based on the experimenter's selection on the two-dimensional image. For example, the two-dimensional image can show the movement state of the mouse in the second activity area. The three-dimensional image can show the movement state of the mouse's left hand limb in the second activity area.

[0027] In response to the depth of field area related to the limbs of the experimental animal specified by the experimenter in the two-dimensional view, the image acquisition unit can send data of the three-dimensional image located in the depth of field area related to the limbs of the experimental animal to the processing unit. Based on this method, the three-dimensional image of a specific limb part of the experimental animal, such as a paw, can be displayed in a clear manner, and the three-dimensional image can display the three-dimensional image of the device located outside the depth of field area in an unclear manner.

[0028] When the experimenter views the 3D image within the specified depth of field area, the image clarity is higher than the 3D image outside the specified depth of field area. When the experimenter views the edge of the depth of field area, the 3D image within the edge is high-definition, while the clarity of the 3D image outside the edge is reduced, thereby prompting the experimenter that the content viewed exceeds the depth of field area, allowing the experimenter to re-plan the depth of field area to view and avoid viewing without a clear target.

[0029] This method can help experimenters focus on the behavior of experimental animals that need to be observed in their designated activity area without being disturbed by other behaviors of experimental animals. For example, the second activity area needs to observe whether the mouse's paws clench, but does not need to observe the mouse's head movements. Based on the observation of three-dimensional images, the head behavior can avoid interfering with the experimenter.

[0030] At the same time, when the experimenter observes the bending behavior of the first finger on the mouse's paw, the second finger may be mistakenly identified as the first finger. The method provided by the present invention can provide the experimenter with an observation area prompt to avoid confusion in the observation position.

[0031] According to a preferred embodiment, the edge of the depth of field area can be set based on the operating area of ​​the robot arm. The display direction of the three-dimensional image or the two-dimensional image can be adjusted based on the operating direction of the experimenter, so that the viewing angle of the image is always given in a way that allows the experimenter to operate the robot arm most appropriately. This edge division method of the high-definition three-dimensional image can use the edge of the robot arm as the segmentation contour to guide the experimenter's line of sight or attention to focus on the viewing area defined by the robot arm.

[0032] The mechanical arm is provided with at least three positions, namely, a first position for holding the experimental animal, a second position for adjusting the holding posture, and a third position for adjusting the movement of the mechanical arm. Preferably, the first position can be the distal end of the claw of the mechanical arm. The second position can be the proximal end of the claw of the mechanical arm. The third position can be the forearm of the mechanical arm.

[0033] Specifically, when the experimental animal is in the first activity area, the processing unit can control the mechanical arm to generate a corresponding operation mode, and use the first position and the second position of the mechanical arm as a calibration line, divide the area defined by the first position and the second position into a depth of field area, and divide the area outside the first position and the second position into outside the depth of field area. When the experimenter selects the depth of field area autonomously, the processing unit can provide the experimenter with a prompt of the depth of field area with an edge based on the calibrated depth of field area. When the experimental animal is in the first activity area, the mechanical arm needs to control the head, tail and body of the experimental animal, and generate a three-dimensional image that the experimenter needs to observe for the body reflection state of the experimental animal. When the experimental animal is large in size, for example, when the experimental animal is a rabbit or a rat, although only the first position of the mechanical arm controls the head of the experimental animal, in order to be able to observe the angle between the head and body of the experimental animal, the area corresponding to the second position of the mechanical arm still needs to be seen. In this operation mode, the mechanical arm can position the head of the experimental animal based on the angle between the head and body of the suspended experimental animal, and suspend the experimental animal to a height of α. Preferably, α is greater than 2cm.

[0034] When the experimental animal is in the second activity area, the processing unit can control the mechanical arm to generate a corresponding operation mode, and use the first position of the mechanical arm as a calibration line, divide the area defined by the first position into a depth of field area, and divide the area outside the first position into outside the depth of field area. When the experimental animal is in the second activity area, since it is only necessary to observe the state of the conditioned reflex of a certain organ of the experimental animal, it is only necessary to observe the position of a certain organ of the experimental animal touched by the mechanical arm. For example, when the mechanical arm touches the auricle of the experimental animal and the auricle reflection of the experimental animal needs to be observed, the depth of field area only needs to locate the auricle of the experimental animal. On the one hand, since the experimental animal may be in a state of long-term motion, continuously shooting images of its auricle state will generate a large amount of garbage data, and the processing unit also needs to filter the image data of the auricle reflection in a large amount of data; on the other hand, the time of the auricle reflection occurs in a very short time when the mechanical arm touches the auricle of the experimental animal. If the auricle of the experimental animal is located based on the working state of the mechanical arm, it may cause the loss of the image that needs to be shot.

[0035] Based on the gripping action of the robot arm, the image of the robot arm when gripping is divided into three-dimensional image clarity, which can effectively select the area range of the high-definition three-dimensional image that needs to be presented. Since the robot arm operation area is often the key part of the experimental animal that needs to be observed and experimented, by focusing on the actual operation area of ​​the robot arm and performing image division, the behavioral images of the experimental animals related to the experimental detection that the experimenter needs to observe can be effectively obtained.

[0036] Based on the edge of the area set by the robotic arm, since the state of the experimental animal must be in the operating area of ​​the robotic arm, the system can confirm whether the image information to be photographed or collected is correct without the need for secondary recognition. Reducing the system's information collection and recognition process can reduce the system's response time or data processing time. At the same time, in a changing experimental environment, the robotic arm can also be used as a positioning base point, so that the system can always obtain reaction information related to the physiological state or reaction state of the experimental animal in a timely manner with the correct positioning base point, and the system can obtain images of the physiological state or reaction state of the experimental animal in a timely and accurate manner.

[0037] According to a preferred embodiment, different activity areas are provided with corresponding sensors, and the sensors can be triggered when the experimental animal enters the corresponding activity area, and the processing unit adjusts the image acquisition position and type of the image acquisition unit based on the sensor being triggered. The image acquisition position can be divided into a first image acquisition area covering the first activity area, a second image acquisition area covering the second activity area, a third image acquisition area covering the third activity area, and a fourth image acquisition area covering the fourth activity area based on different activity areas. The image acquisition type includes close-up images for collecting experimental animal behavior information and long-range images for collecting experimental animal position information. Preferably, the close-up image can be used to collect dynamic changes in the extremities or partial tissues of the experimental animal. The long-range image can be used to collect the position changes of the experimental animal in different activity areas to confirm the walking route of the experimental animal. The walking route of the experimental animal includes at least four types: normal walking, non-straight walking, circling to the paralyzed side, and tilting to the paralyzed side.

[0038] The third activity area of ​​each movement column of the movement base can be set as a flat straight channel. The third activity area of ​​the movement base used to provide planar movement detection for experimental animals is set as a linear plane.

[0039] The fourth activity area of ​​each activity column of the activity base is provided with a balance bar, one end of which is connected to the end of the third activity area so that the experimental animals passing through the third activity area can move to the balance bar based on driving or enticement. Preferably, the balance bar is configured as a retractable balance bar so that the fourth activity area is suitable for experimental animals of different sizes.

[0040] The animal behavior scores before and after stem cell transplantation mainly include movement scores, flat ground walking, sensory experiments, balance beam experiments, loss of reflexes and abnormal movements.

[0041] According to a preferred embodiment, the experimental system involved in the present invention is suitable for bone marrow mesenchymal stem cell transplantation and umbilical cord mesenchymal stem cell transplantation.

[0042] According to a preferred embodiment, the experimental animals involved in the present invention can be rats, mice, rabbits and other animals suitable for stem cell transplantation experiments.

[0043] The present invention provides an experimental system based on stem cell transplantation, the system comprises an experimental operation unit for guiding an experimental animal to have a detectable behavior, a data acquisition unit capable of collecting images and electromyographic signals of the experimental animal, and a processing unit for evaluating the neurological behavior of the experimental animal. The experimental operation unit is provided with a first activity area for providing the experimental animal with limb motor sensation detection, such as Figure 1As shown, when the experimental animal enters the first activity area, the processing unit can control the experimental operation unit to grasp the tail, head and trunk of the experimental animal in turn, and the data acquisition unit can switch data acquisition when the experimental operation unit grasps different parts of the experimental animal. When the experimental operation unit grasps the tail of the experimental animal, the data acquisition unit can capture images of the experimental animal. When the experimental operation unit grasps the head or trunk of the experimental animal, the data acquisition unit can capture electromyographic signals of the experimental animal to obtain data on different behavioral states of the experimental animal, so that the processing unit can obtain data on the behavioral states of different experimental animals under different influencing factors. The processing unit performs a 0 / 1 evaluation on the corresponding behaviors of different experimental animals based on the mean of different data of the same behavior of all experimental animals.

[0044] According to a preferred embodiment, the electromyographic signal is used to sense whether a delay occurs in the limb muscles of the experimental animal when it is subjected to different stimuli.

[0045] According to a preferred embodiment, each activity area and each movement column of the motion base is provided with a partition. Preferably, the partition provided between each activity area can be closed based on the end of the detection project of the activity area, so that the experimental animal can enter the next activity area. The partition is controlled by the processing unit. When the processing unit obtains the image data or electromyographic signal data required for the activity area, the processing unit controls the partition to close.

[0046] The sensory experiment is to judge whether the experimental animals' senses are normal or not by the speed of muscle reaction. When the experimental animals are stimulated, the speed of the experimental animals' perception of external stimuli is judged by obtaining information on whether their muscle conditioned reflexes are delayed or not. Since experimental animals are generally small in size and easily startled, it is more accurate to directly record their electromyographic signals to judge their reaction speed than to observe the dynamic changes of their limbs.

[0047] When the experimental animals enter the second activity area, Figure 2 As shown, the processing unit controls the image acquisition unit to acquire close-up images of the experimental animal. At the same time, the processing unit can control the auricle reflex detection component to start working based on the experimental animal entering the second activity area. The processing unit can control the auricle reflex detection component to touch the auricle of the experimental animal based on the auricle position of the experimental animal acquired by the image processing unit. The image processing unit acquires the image of the experimental animal and sends the image data to the processing unit. The processing unit determines whether the experimental animal has a head shaking reaction. Preferably, the head shaking reaction of the experimental animal is recorded as 0, and the no head shaking reaction is recorded as 1.

[0048] Based on the movement of the experimental animal, when the experimental animal enters the detection area of ​​the corneal reflection detection component, the processing unit controls the corneal reflection detection component to touch the cornea of ​​the experimental animal. The image processing unit collects the image of the experimental animal and sends the image data to the processing unit. The processing unit determines whether the experimental animal has a blink reaction. Preferably, the blink of the experimental animal is recorded as 0, and no blink reaction is recorded as 1.

[0049] Based on the movement of the experimental animal, when the experimental animal enters the detection area of ​​the sound reflection detection component, the processing unit controls the sound reflection detection component to emit a preset noise. The image processing unit collects the image of the experimental animal and sends the image data to the processing unit. The processing unit determines whether the experimental animal has an escape movement. Preferably, the experimental animal's escape movement response is recorded as 0, and no escape movement response is recorded as 1.

[0050] When the experimental animals enter the third activity area, Figure 3 As shown, the processing unit can control the image acquisition unit to acquire a distant image of the experimental animal based on the experimental animal entering the third activity area. The processing unit receives the distant image of the experimental animal transmitted by the image acquisition unit to confirm the displacement trajectory of the experimental animal. Based on the extension direction of the third activity area, it is confirmed whether the displacement trajectory of the experimental animal is offset and the type of offset.

[0051] When the experimental animals enter the fourth activity area, Figure 3 As shown, the processing unit controls the image acquisition unit to acquire close-up images of the experimental animal. Based on the posture of the experimental animal and the time it stays on the balance pole, the processing unit classifies the performance of the experimental animal on the balance pole and provides a corresponding evaluation score based on the category in which it is located. BRIEF DESCRIPTION OF THE DRAWINGS

[0052] Figure 1 It is a structural schematic diagram of an implementation mode provided by the present invention;

[0053] Figure 2 is a structural schematic diagram of a second activity area provided by the present invention;

[0054] Figure 3 It is a schematic diagram of the structure of the third activity area and the fourth activity area provided by the present invention.

[0055] Reference numerals list

[0056] 100: first active area; 110: robotic arm; 200: second active area; 210: auricle reflection detection component; 220: corneal reflection detection component; 230: sound reflection detection component; 300: third active area; 310: image acquisition unit; 400: fourth active area; 410: balance bar; 500: moving column; 600: first direction; 700: second direction; 800: moving base plate. DETAILED DESCRIPTION

[0057] The following is a detailed description with reference to the accompanying drawings.

[0058] Example 1

[0059] The present invention relates to a system for tail lifting experiment. The present invention relates to a system for sensory experiment.

[0060] The system of the present invention is suitable for use in rats.

[0061] Method for establishing rat model of cerebral hemorrhage: rats were anesthetized by intraperitoneal injection of 0.3% pentobarbital (0.1ml / 100g). After successful anesthesia, rats were fixed with a brain stereotaxic instrument. The injection point of the caudate nucleus was 0.1mm in front of the bregma, 3.0mm to the right of the sagittal suture, and 5.5mm deep. The skin was incised in the middle of the scalp with routine disinfection to expose the bregma point, adjust the locator to the injection point, and mark it. A bone drill was used to drill a hole, and 2μl of type IV collagenase was drawn with a microinjector and injected at the injection point. The injection time was not less than 5min. After the injection, the needle was retained for 10min, the drill hole was sealed with bone wax, and the skin was sutured after local iodine disinfection.

[0062] Method for establishing rat model of cerebral hemorrhage after umbilical cord mesenchymal stem cell transplantation: 6 hours after the successful preparation of the cerebral hemorrhage model, the rat was anesthetized again, and the rat was re-fixed on the stereotaxic instrument, the skin was disinfected, the sutures were cut, and the anterior bregma was exposed again. Under sterile conditions, the transplantation site of the rat was located, and 2μl of HUC-MSCs suspension was slowly injected into the injured side of the rat with a microinjector at a speed of 1μl / min. The needle was withdrawn after leaving it in for 30 minutes, the wound was sealed with bone wax, the skin was disinfected and sutured, and the rat was sent back to the breeding room for routine feeding.

[0063] The motion base 800 is provided with six motion columns 500. Two normal rats are placed in two motion columns 500, which are labeled a and b. Two cerebral hemorrhage model rats are placed in two motion columns 500, which are labeled c and d. Two cerebral hemorrhage model rats after umbilical cord mesenchymal stem cell transplantation are placed in two motion columns 500, which are labeled e and f. Six rats are placed in the first activity area 100 of each motion column 500 of the motion base 800 in the order of a, c, e, b, d, and f.

[0064] Each movement column 500 of the movement base 800 is provided with a mechanical arm 110 in the first movement area 100. The mechanical arm 110 can at least grasp the tail, head or forelimb of the rat.

[0065] When the rat enters the first activity area 100, the processing unit can control the experimental operation unit to grab the rat's tail, head and torso in turn, and the data acquisition unit can switch data acquisition when the experimental operation unit grabs different parts of the rat, wherein when the experimental operation unit grabs the rat's tail, the image acquisition unit 310 can capture images of the rat, and when the experimental operation unit grabs the rat's head or torso, the data acquisition unit can collect electromyographic signals of the rat to obtain data on different behavioral states of the rat, so that the processing unit can obtain data on the behavioral states of different rats under different influencing factors, and the processing unit performs a 0 / 1 evaluation on the corresponding behaviors of different rats based on the mean of different data of the same behavior of all rats.

[0066] Specifically, when a rat enters the first activity area 100, the processing unit controls the mechanical arm 110 provided in each activity column to grab the rat's tail and suspend the rat by its tail one meter in the air. The image acquisition unit 310 acquires a close-up image of the rat.

[0067] The processing unit confirms the angle between the head and body of the rat based on the received image information of the rat. When there is no angle between the head and the vertical axis of the body or the angle is ≤10° and the limbs are stretched to the ground, the evaluation score given by the processing unit is 0. When the vertical axis of the head and the body deviates from the vertical axis by >10°, the forelimbs are flexed or the hindlimbs are flexed, the evaluation score given by the processing unit is 1. This test is a visual experiment for rats.

[0068] Based on the obtained image data related to the rat lifting its tail, the processing unit controls the mechanical arm 110 of the corresponding motion column 500 to grab the rat's front paw, and slowly tilts 45° from 10 cm above the desktop to the desktop, so that the desktop is located in front of the rat or on the paralyzed side. The processing unit confirms the rat's limb movements based on the received rat's limb electromyographic signals. When the change time of the rat's forelimb electromyographic signals is less than 1 second, the evaluation score given by the processing unit is 0. When the change time of the rat's forelimb electromyographic signals is greater than 1 second, the evaluation score given by the processing unit is 1. This detection is a tactile experiment on rats.

[0069] Example 2

[0070] The present invention relates to a system for reflex experiments.

[0071] This system is suitable for rats.

[0072] The motion base plate 800 is provided with six motion columns 500. Two normal rats are placed in two motion columns 500, which are labeled a and b. Two cerebral hemorrhage model rats are placed in two motion columns 500, which are labeled c and d. Two cerebral hemorrhage model rats after umbilical cord mesenchymal stem cell transplantation are placed in two motion columns 500, which are labeled e and f. Six rats are placed in the first activity area 100 of each motion column 500 of the motion base plate 800 in the order of a, c, e, b, d, and f. After completing all the detection processes in the first activity area 100, the second activity area 200 is opened.

[0073] When the rat enters the second activity area 200, the processing unit controls the image acquisition unit 310 to acquire a close-up image of the rat. At the same time, the processing unit can control the auricle reflection detection component 210 to start working based on the rat entering the second activity area 200. The mechanical arm 110 is suitable for the second activity area 200.

[0074] The processing unit can control the mechanical arm 110 to grab the rat's trunk and control the auricle reflection detection component 210 to touch the rat's auricle based on the position of the rat's auricle collected by the image processing unit. The image processing unit collects the image of the rat and sends the image data to the processing unit. The processing unit determines whether the rat has a head shaking reaction. Preferably, the rat's head shaking reaction is recorded as 0, and no head shaking reaction is recorded as 1.

[0075] Based on the movement of the rat, when the rat enters the detection area of ​​the corneal reflection detection component 220, the processing unit controls the mechanical arm 110 to grab the rat's trunk and controls the corneal reflection detection component 220 to touch the rat's cornea. The image processing unit collects the image of the rat and sends the image data to the processing unit. The processing unit determines whether the rat has a blink reaction. Preferably, the rat blinks as 0, and no blink reaction is recorded as 1.

[0076] Based on the movement of the rat, when the rat enters the detection area of ​​the sound reflection detection component 230, the processing unit controls the sound reflection detection component 230 to emit a preset noise. The image processing unit collects the image of the rat and sends the image data to the processing unit. The processing unit determines whether the rat has an escape movement. Preferably, the escape movement reaction of the rat is recorded as 0, and the absence of the escape movement reaction is recorded as 1.

[0077] Example 3

[0078] When the rat enters the third activity area 300, the processing unit can control the image acquisition unit 310 to acquire a distant image of the rat based on the rat entering the third activity area 300. The processing unit receives the distant image of the rat transmitted by the image acquisition unit 310 to confirm the displacement trajectory of the rat. Based on the extension direction of the third activity area 300, it is confirmed whether the displacement trajectory of the rat is offset and the type of offset.

[0079] Example 4

[0080] When the rat enters the fourth activity area 400, the processing unit controls the image acquisition unit 310 to acquire close-up images of the rat. Based on the posture of the rat and the time it stays on the balance pole 410, the processing unit classifies the performance of the rat on the balance pole 410 and provides a corresponding evaluation score based on the category in which the rat is located.

[0081] According to the performance of the rats on the balance bar 410, the performance of the rats was divided into six categories, namely, the rat was stable on the balance bar 410 (0), the rat grasped the balance bar 410 (1), the rat held the balance bar 410 tightly with one limb hanging down (2), the rat held the balance bar 410 tightly with one limb hanging down for more than 60 seconds (3), the rat fell but remained on the balance bar 410 for more than 40 seconds (4), the rat fell but remained on the balance bar 410 for more than 20 seconds (5), and the rat fell directly (6).

[0082] Example 5

[0083] The present invention provides a balance bar 410 device for detecting the balance ability of experimental animals.

[0084] The balancing pole 410 device includes a retractable balancing pole 410. The balancing pole 410 is hinged to the movable surface of the third movable area 300. An image acquisition unit 310 is disposed at one end of the balancing pole 410 opposite to the third movable area 300. Preferably, the image acquisition unit 310 is a camera that can transmit image information to a processing unit.

[0085] Example 6

[0086] The image acquisition unit 310 includes a three-dimensional scanner and a camera. The three-dimensional scanner forms a three-dimensional image of an animal model, such as a three-dimensional image of a mouse, based on point cloud technology. The camera-based image acquisition obtains two-dimensional image information.

[0087] The same animal model under inspection in the two-dimensional image and the three-dimensional image adopts the same encoding, which is conducive to the synchronous display and conversion of the two-dimensional image and the three-dimensional image in the same animal model.

[0088] The method for obtaining three-dimensional data of an animal model includes the following steps:

[0089] Acquire the three-dimensional point cloud information of the animal model through a three-dimensional scanner, establish a three-dimensional Cartesian coordinate system with the three-dimensional scanner as the coordinate center, and calibrate the Cartesian coordinates of each point in the three-dimensional point cloud;

[0090] With the 3D scanner as the coordinate center, a 3D cylindrical coordinate system is established, and the conversion relationship between the Cartesian coordinates and the cylindrical coordinates of each point in the 3D point cloud is established, and the 3D point cloud in the Cartesian space coordinate system is mapped to the cylindrical coordinate system;

[0091] The cylinder of the three-dimensional cylindrical coordinate system is unfolded to construct a two-dimensional cylindrical coordinate system, and a conversion relationship between the cylindrical coordinates of each point in the three-dimensional point cloud and the cylindrical coordinates of the two-dimensional cylindrical coordinate system is established. The three-dimensional point cloud in the cylindrical coordinate system is mapped to the two-dimensional cylindrical coordinate system to generate the two-dimensional pixel coordinates of the animal model.

[0092] The method for obtaining three-dimensional point cloud data of a measured object by a three-dimensional scanner comprises the following steps:

[0093] A light source, used for projecting a plurality of stripe patterns on the animal model, wherein the number of stripes in the stripe pattern is greater than 15;

[0094] Left and right cameras, used to synchronously acquire 2D left and 2D right images of the animal model;

[0095] A three-dimensional module for synchronously acquiring depth maps of animal models;

[0096] A stripe matching module, for guiding the matching of stripes of the left and right images according to the depth map, including back-projecting the depth map into the left and right images for matching;

[0097] The 3D reconstruction module is used to reconstruct the corresponding stripes matched in the left and right images into 3D point cloud data.

[0098] It should be noted that the above-mentioned specific embodiments are exemplary, and those skilled in the art can come up with various solutions inspired by the disclosure of the present invention, and these solutions also belong to the disclosure scope of the present invention and fall within the protection scope of the present invention. Those skilled in the art should understand that the present invention specification and its drawings are illustrative and do not constitute a limitation of the claims. The scope of protection of the present invention is defined by the claims and their equivalents. The present invention specification contains multiple inventive concepts, such as "preferably", "according to a preferred embodiment" or "optionally", all of which indicate that the corresponding paragraph discloses an independent concept, and the applicant reserves the right to file a divisional application based on each inventive concept. Throughout the text, the feature guided by "preferably" is only an optional method and should not be understood as a must-have setting. Therefore, the applicant reserves the right to abandon or delete the relevant preferred features at any time.

Claims

1. A processing unit, characterized in that: Used to detect experimental animal behavior, the processing unit can control the mechanical arm (110) and the image acquisition unit (310); The processing unit is configured to: When experimental animals enter the designated activity area, controlling the mechanical arm (110) to generate an operation mode corresponding to the designated activity area so as to grasp a designated part of the experimental animal, Determining the behavior and / or behavior trajectory of the experimental animal based on the image data of the experimental animal sent by the image acquisition unit (310); in, The processing unit controls the image acquisition unit (310) to acquire a near-view image or a far-view image corresponding to a designated activity area of ​​the experimental animal. And in response to the experimenter's selection on the two-dimensional image, the image acquisition unit (310) is controlled to generate an image that is displayed in parallel on the interactive terminal in two-dimensional and three-dimensional modes.

2. The processing unit according to claim 1, characterized in that The processing unit is further configured to: In response to a depth of field area related to a limb of an experimental animal specified by an experimenter in a two-dimensional view, data of a three-dimensional image located in the depth of field area related to a limb of the experimental animal sent by the image acquisition unit (310) is received.

3. The processing unit according to claim 1 or 2, characterized in that: The edge of the depth of field area can be set based on the operating area for planar motion detection of experimental animals; The mechanical arm (110) is provided with at least three positions, including a first position for holding the experimental animal, a second position for adjusting the holding posture, and a third position for adjusting the movement of the mechanical arm; The image acquisition unit (310) divides the depth of field area according to the depth of field area division method corresponding to the designated area and the first position, the second position and the third position.

4. The processing unit according to claim 3, characterized in that In a first activity area (100) for detecting extremity movement sensation of an experimental animal, the processing unit uses the first position and the second position of the mechanical arm (110) as calibration lines, and divides the area defined between the first position and the second position into a depth of field area; In the second activity area (200) used for experimental animal reflex detection, the processing unit uses the first position of the robotic arm (110) as a calibration line, divides the area defined by the first position into a depth of field area, and divides the area outside the area defined by the first position into an area outside the depth of field area.

5. An experimental operation device, which can be connected to and controlled by a processing unit, characterized in that: It comprises a motion base plate (800) for guiding an experimental animal to produce a detection behavior, a movable mechanical arm (110), an auricle reflection detection component (210), a corneal reflection detection component (220) and a sound reflection detection component (230); A partition is provided between each activity area of ​​the motion base plate (800), and the partition can be closed based on the completion of the detection project of the activity area, so that the experimental animal can enter the next activity area; When the experimental animal enters the designated activity area, the mechanical arm (110) grabs the designated part of the experimental animal according to the operation mode corresponding to the designated activity area. Under the control of the processing unit, the auricle reflection detection component (210) touches the auricle of the experimental animal; the corneal reflection detection component (220) touches the cornea of ​​the experimental animal; Under the control of the processing unit, the sound reflection detection component (230) emits a preset noise to enable the experimental animal to generate an escape movement response.

6. The experimental operation device according to claim 5, characterized in that: The mechanical arm (110) is provided with at least three positions, including a first position for holding the experimental animal, a second position for adjusting the holding posture, and a third position for adjusting the movement of the mechanical arm; In a first activity area (100) for detecting extremity movement sensation of experimental animals, the first position and the second position of the mechanical arm (110) are used as calibration lines to divide the area defined between the first position and the second position into a depth of field area; In the second activity area (200) used for experimental animal reflex detection, the first position of the mechanical arm (110) is used as a calibration line to divide the area defined by the first position into a depth of field area, and to divide the area outside the area defined by the first position into an area outside the depth of field area.

7. The experimental operation device according to claim 6, characterized in that: When the robot arm (110) touches the auricle of the experimental animal and needs to observe the auricle reflection of the experimental animal, the depth of field area only needs to locate the auricle of the experimental animal.

8. An interactive terminal, characterized in that: When the experimental animal enters the designated activity area, the interactive terminal displays a close-up image of the experimental animal's behavior information and a long-range image of the experimental animal's location information; The interactive terminal provides a two-dimensional image of the experimental animal in response to an operation instruction of the experimenter, and displays the image in two-dimensional and three-dimensional modes in parallel based on the selection of the experimenter on the two-dimensional image; In which, in response to a depth of field area related to the limbs of the experimental animal specified by the experimenter based on the two-dimensional image, the interactive terminal displays a three-dimensional image within the depth of field area related to the limbs of the experimental animal.

9. The interactive terminal according to claim 8, characterized in that: The same detected experimental animal in the two-dimensional image and the three-dimensional image adopts the same code, and the interactive terminal synchronously displays and converts the two-dimensional image and the three-dimensional image of the same experimental animal.

10. The interactive terminal according to claim 8 or 9, characterized in that: The display direction of the three-dimensional image or the two-dimensional image is adjusted based on the operation direction of the experimenter, so that the viewing angle of the image is always displayed on the interactive terminal in a way that enables the experimenter to operate the robotic arm most appropriately.

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