Automatic mouse von Frey pain detector with three-degree-of-freedom mechanical arm

Abstract

The utility model belongs to but not limited to the technical field of animal experiment equipment, and discloses a three-degree-of-freedom mechanical arm automatic mouse von Frey pain detector which comprises an integrated experiment box, and a metal grid plate is arranged in the integrated experiment box and divides the integrated experiment box into an upper layer and a lower layer; the upper layer is a light-transmitting transparent experiment box, is separated by a hard opaque partition plate, is used for placing an experiment mouse and is provided with a visible light camera, and the lower layer is a light-proof camera obscura, and is provided with a three-degree-of-freedom mechanical arm and an infrared camera; a von Frey mechanical stimulation needle is arranged on the three-degree-of-freedom mechanical arm, and a high-precision pressure sensor is arranged at the von Frey mechanical stimulation needle. The utility model provides experimental equipment with high precision and high automation level, and by accurately controlling the mechanical pain stimulation to the experimental mouse, the accurate quantitative determination of the pain response threshold of the mouse or the rat is realized, so that objective, accurate and repeatable experimental data is provided.

Description

Technical Field

[0001] This utility model belongs to, but is not limited to, the field of animal experimental equipment technology, and particularly relates to a three-degree-of-freedom robotic arm automatic mouse von Frey pain measurement device. Background Technology

[0002] Pain is an unpleasant sensory or emotional experience associated with actual or potential tissue damage, and it is one of the most common patient complaints in clinical practice. It not only causes physical suffering but can also lead to psychological burdens and a decline in patients' quality of life. Research into pain and analgesia mechanisms and the development of related drugs remain important topics in current medical research.

[0003] Research on the mechanisms of pain and analgesia, as well as drug development, often requires the use of laboratory animals. Mice and rats are currently the most commonly used model animals in this field. Pain behavior detection is crucial in pain and analgesia research. Generally, this involves applying specific noxious or non-noxious stimuli to mice and quantitatively measuring the stimulus threshold that induces a pain response. This reflects the mouse's pain threshold, thereby determining the mouse's sensitivity to stimuli and assessing indicators such as the effectiveness of the mouse pain model or the analgesic effect of drugs.

[0004] Mechanical stimuli such as poking, pressing, or squeezing are forms of noxious or non-noxious stimuli, and the pain they cause is called mechanical pain. Currently, the commonly used laboratory method for detecting mechanical pain is the von Frey test. The basic method involves applying mechanical pressure to the center of a mouse's hind paw using von Frey filaments (also known as ciliary mechanical stimuli needles), and measuring the threshold at which the mouse responds to the mechanical stimulus with pain (raising or lowering the paw).

[0005] The traditional von Frey analgesia test applies varying degrees of mechanical pressure to a mouse's paw using nylon filaments of different diameters and stiffnesses. Pain response is determined by visually observing the mouse's paw lifting or retraction, and the pain threshold is determined based on the strength of the nylon filament used. This traditional test is not only complex and cumbersome, requiring the experimenter to start with a relatively weak von Frey filament (e.g., 0.04g) and then gradually change filaments according to different strength gradients (0.07g, 0.16g, 0.40g, 0.60g, 1.0g, 1.4g, 2.0g, 4.0g, 6.0g, 8.0g, etc.), repeatedly measuring the mechanical stimulation, but also introduces significant subjectivity due to the experimenter's manual control over the direction, location, and intensity of the stimulation, affecting the accuracy and precision of the measurement.

[0006] Current electronic von Frey analgesics address the aforementioned problems of traditional von Frey analgesia. Based on the traditional von Frey method, it uses the same mechanical stimulation needle and, through automated control, linearly increases the intensity of mechanical stimulation within a specified range at a predetermined slope. A force sensor detects and records the stimulation threshold and withdrawal time that triggers the withdrawal response in mice, improving measurement accuracy and freeing the experimenter's hands, significantly reducing subjectivity. However, the automation level of commercially available electronic von Frey analgesics still needs improvement. Currently, the needle tip still requires manual control to align with the sole of the foot, which is labor-intensive and the experimental animals are susceptible to operator interference. Furthermore, in practice, inaccurate manual positioning often causes the mechanical needle to collide with the metal mesh plate supporting the experimental animal, damaging the sensor and shortening the lifespan of the analgesics. In addition, the electronic von Frey analgesics rely solely on the operator's visual judgment and force sensor sensing to determine the pain response. However, rats exhibit rapid pain response (milliseconds), leading to significant subjective errors in visual assessment. Force sensors can only determine whether a rat withdraws its paw, but struggle to distinguish between pain-induced paw withdrawal and withdrawal caused by other factors, such as spontaneous animal movement, thus limiting measurement accuracy. The accuracy of electronic von Frey pain measurement devices urgently needs improvement.

[0007] Therefore, there is an urgent need for a highly automated, objectively accurate, and low-cost rat pain measurement scheme that can improve the accuracy of measurement results while reducing subjective errors and the uncertainty of results caused by the experimenter's influence on the animals. Utility Model Content

[0008] To address the problems of existing technologies, this invention provides a three-degree-of-freedom robotic arm-based automatic mouse pain measurement device that features high automation, high accuracy, small size, storable experimental data, and applicability in multiple scenarios. It utilizes machine learning and a three-degree-of-freedom robotic arm design to solve the problems of low accuracy and low automation in existing pain measurement methods.

[0009] This invention is implemented as follows: a three-degree-of-freedom robotic arm automatic mouse von Frey pain measurement device, including an integrated experimental box, a three-degree-of-freedom robotic arm, a von Frey mechanical stimulation needle, a high-precision pressure sensor, a visible light camera, an infrared camera, and a mouse posture analysis and computing platform.

[0010] The integrated experimental chamber has an internal metal mesh plate that divides it into upper and lower layers. The upper layer is a transparent chamber that allows light to pass through, separated by a rigid, opaque partition. It is used to house the experimental mice and is equipped with a visible light camera. The lower layer is an opaque dark chamber that houses a three-degree-of-freedom robotic arm and an infrared camera. The three-degree-of-freedom robotic arm is equipped with a von Frey mechanical stimulation needle, and a high-precision pressure sensor is installed at the von Frey mechanical stimulation needle.

[0011] Furthermore, a rigid, opaque partition is placed on the metal mesh plate, allowing for simultaneous experiments with two rats or four mice on the upper layer.

[0012] Furthermore, the three-degree-of-freedom robotic arm is driven by an electric servo motor to move the von Frey mechanical stimulation needle in the XYZ directions, so as to move to different positions on the soles of the mouse's feet.

[0013] Furthermore, the movement range of the robotic arm in the XYZ directions is as follows: X direction 0-50cm, Y direction 0-50cm, Z direction 0-20cm.

[0014] Based on the above technical solutions and the technical problems solved, the advantages and positive effects of the technical solution to be protected by this utility model are as follows:

[0015] First, this utility model relates to a three-degree-of-freedom robotic arm automated mouse pain measurement device, designed to provide a high-precision, highly automated experimental device for research on pain and analgesia mechanisms and drug development. This device aims to quantitatively determine the pain response threshold of mice or rats by precisely controlling the mechanical stimulation of experimental mice, thereby providing researchers with objective, accurate, and repeatable experimental data. Specifically:

[0016] Designed and manufactured based on the principle of pain measurement using mechanical stimulation needles, it has a simple structure and is easy to assemble and operate.

[0017] The three-degree-of-freedom robotic arm device offers flexible control and can simultaneously monitor multiple mice, achieving automated mechanical pain measurement control, improving experimental efficiency and accuracy, and enhancing experimental repeatability.

[0018] Equipped with a high-precision pressure sensor, it can adjust the maximum force, the linear rate of change of the force, the magnitude of the initial force, and the duration of the initial force.

[0019] Equipped with a monitoring camera, it records and stores the behavioral changes of mice during acupuncture in real time, and analyzes the degree of pain response of mice through machine learning algorithms, thereby automating the storage, statistics and analysis of experimental data.

[0020] The device of this utility model is made of readily available and inexpensive materials, is easy to assemble, and can be widely used in various situations.

[0021] Compared with the prior art, this utility model has significant innovation and advantages in the following aspects:

[0022] First, in this three-degree-of-freedom robotic arm automated mouse von Frey pain assessment device, the application of each hardware component has brought corresponding technological advancements, improving the automation, accuracy, and repeatability of the experiment. The specific technological advancements of each hardware component are as follows:

[0023] 1) Rigid, opaque partition (1):

[0024] A rigid, opaque partition effectively separates the experimental areas, preventing interference between mice and ensuring experimental independence and data accuracy. In traditional methods, mice may be affected by the visual or olfactory senses of other subjects, leading to unstable results. This partition ensures each mouse can react independently, eliminating the influence of environmental factors on the data. Simultaneously, it blocks external light sources from interfering with the lower infrared camera, improving its detection accuracy.

[0025] 2) Metal mesh plate (2):

[0026] The metal mesh platform provides a support platform for the mice while allowing the von Frey mechanical stimulation needle to pass underneath and directly stimulate the soles of the mice's feet. This design is more flexible than traditional flat supports, allowing for precise insertion of the mechanical needle without interfering with the mice's natural movement. Compared to previous experimental devices using flat platforms, the mesh platform enables more accurate application of mechanical stimulation and ensures that the mice remain in a natural posture during activity, greatly improving the stability and reproducibility of the experiment.

[0027] 3) Three-degree-of-freedom robotic arm (3):

[0028] The three-degree-of-freedom robotic arm achieves precise control over the position of the von Frey mechanical stimulation needle through precise movement in the X, Y, and Z directions. Compared to manually operated or fixed-position mechanical devices, the robotic arm significantly improves the automation of the experiment, ensuring that each stimulation is accurately positioned at the designated location on the sole of the mouse's foot. This automated and precise control not only improves experimental efficiency and reduces errors from human intervention, but also makes the data from repeated experiments more consistent and comparable.

[0029] 4) Infrared camera (4):

[0030] An infrared camera, installed in the lower dark chamber, is specifically designed to monitor the location of heat sources on the soles of the mice's feet. Compared to traditional visible light cameras, infrared cameras can monitor foot temperature changes in real time without light interference, helping researchers more accurately capture the mice's thermal responses to von Frey mechanical stimuli. The use of infrared cameras provides a more objective physical indicator for assessing pain responses; in particular, local temperature changes on the soles of the feet can directly reflect the physiological response to pain, which significantly improves the accuracy of pain measurement.

[0031] 5) Visible light camera (5):

[0032] A visible light camera is installed in the upper transparent experimental chamber to record the overall movement and posture of the experimental mice. Compared to traditional single-camera systems, this camera not only captures the full-body movements of the mice but also allows for detailed motion analysis through a posture analysis platform. It provides more comprehensive data support for the experiment, enabling researchers to simultaneously observe the direct responses of mechanical stimuli to the mice (such as postural changes) and subsequent effects (such as slowed movement and abnormal behavior), thus improving the comprehensiveness and depth of the experiment.

[0033] 6) Integrated experimental box (6):

[0034] The integrated experimental chamber design significantly improves the structural integration and ease of operation of the experimental device. Traditional pain measurement instruments typically require multiple separate components to work together, while this integrated design combines different components into a single experimental chamber, reducing the complexity of connections between devices and improving portability and experimental efficiency. Simultaneously, the transparent upper layer and opaque lower layer effectively isolate external light interference, further ensuring the accuracy of experimental data.

[0035] 7) von Frey mechanical stimulation needle (7):

[0036] The von Frey mechanical stimulator is used to apply precise mechanical pressure stimulation. Compared to the manually operated von Frey needle, the mechanized design significantly improves the stability and controllability of the pressure. Unlike previous methods of manually adjusting stimulation, this mechanical needle, controlled by a three-degree-of-freedom robotic arm, can precisely apply pressure without interfering with the activity of the laboratory mice, and measure the pressure magnitude in real time, ensuring consistency of pressure applied in each experiment and greatly reducing experimental errors.

[0037] 8) High-precision pressure sensor (8):

[0038] A high-precision pressure sensor is used to monitor the pressure applied by the von Frey mechanical stimulation needle in real time. Unlike traditional quantitative application of mechanical force, the sensor can accurately feed back the applied pressure and dynamically adjust it during the experiment, ensuring the accuracy and consistency of the pressure throughout the experiment. Its introduction improves the accuracy of pressure application, avoids errors in experimental data caused by improper force application, and provides a guarantee for the reliability of experimental results.

[0039] 9) Mouse posture analysis and computing platform (9):

[0040] The mouse posture analysis platform automatically analyzes posture changes in laboratory mice after receiving von Frey mechanical stimulation by combining image data from visible light and infrared cameras. This automated posture analysis platform eliminates subjective errors that may arise from manual observation, significantly improving the accuracy and objectivity of data analysis. Through real-time monitoring and computation, the platform can quickly generate experimental reports, helping researchers more intuitively assess the mice's pain response and reducing the time cost of subsequent data processing.

[0041] The application of these hardware devices has greatly improved the automation level of experimental setups, data accuracy, and experimental repeatability, providing more efficient and precise technical support for pain response research in biomedical experiments.

[0042] Second, the expected revenue and commercial value after the transformation of the technical solution of this utility model are as follows: Expected revenue: RMB 1 million to 5 million. The product will be manufactured as an automatic mouse pain detector and sold to domestic universities and research institutes.

[0043] This invention fills a technological gap in the domestic and international industry: it proposes a highly automated, objectively accurate, and low-cost mouse analgesia measurement solution, filling the gap in high-precision automated mouse analgesia devices. This invention solves a long-standing technical problem that has remained unsolved: the automation level of electronic von Frey analgesics in the domestic and international industry still needs improvement. Currently, analgesics still require manual control to align the needle tip with the sole of the foot, resulting in cumbersome experiments, high manpower costs, and susceptibility of experimental animals to operator interference. Furthermore, in actual operation, inaccurate manual positioning often causes the mechanical needle to collide with the metal mesh plate supporting the experimental animal, damaging the sensor and shortening the lifespan of the analgesic device. In addition, electronic von Frey analgesics rely solely on the operator's visual judgment and force sensor sensing to determine pain response. However, mice exhibit rapid pain response, leading to significant subjective errors in visual assessment; the force sensor can only determine whether the mouse withdraws its paw, but it cannot distinguish between pain-induced paw withdrawal and paw withdrawal caused by other reasons such as spontaneous animal movement, limiting the accuracy of the measurement. Attached Figure Description

[0044] Figure 1 This is a structural diagram of the three-degree-of-freedom robotic arm automatic mouse von Frey pain measurement device provided in this embodiment of the utility model;

[0045] In the diagram: 1. Rigid opaque partition; 2. Metal mesh plate; 3. Three-degree-of-freedom robotic arm; 4. Infrared camera; 5. Visible light camera; 6. Integrated experimental chamber; 7. von Frey mechanical stimulation needle; 8. High-precision pressure sensor; 9. Mouse posture analysis and computing platform. Detailed Implementation

[0046] To make the objectives, technical solutions, and advantages of this utility model clearer, the following detailed description is provided in conjunction with embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of this utility model.

[0047] This invention mainly consists of a three-degree-of-freedom robotic arm, upper and lower experimental chambers, a high-precision pressure sensor, a dual-camera system, and a mouse posture analysis and computing platform. The core feature of this device is the use of a three-degree-of-freedom robotic arm to precisely move in the X, Y, and Z directions, combined with a high-precision force sensor, to achieve mechanical stimulation of the soles of the experimental mice's feet. The device uses the upper and lower camera systems to monitor and record the mice's movement posture and pain response in real time, and then uses machine learning algorithms to analyze this data to generate a quantitative pain index model.

[0048] like Figure 1 As shown, the specific working principle of the hardware components in this three-degree-of-freedom robotic arm automatic mouse von Frey pain measurement device is as follows:

[0049] Rigid Opaque Partition 1:

[0050] A rigid, opaque partition is located in the center of the experimental chamber, primarily used to isolate the area where the experimental mice are placed from other components. It effectively prevents visual and physical interference between the mice, ensuring the independence of the experiment. Simultaneously, the partition blocks external light from entering the lower dark chamber area, preventing interference with the infrared camera 4. This partition design ensures the stability and accuracy of the experimental environment, providing the mice with a controlled and minimally disturbed environment.

[0051] Metal mesh plate 2:

[0052] The metal mesh plate, a key component mounted in the middle of the integrated experimental chamber 6, supports the mouse's body and allows the von Frey mechanical stimulation needle 7 to pass over the lower three-degree-of-freedom robotic arm 3. The mesh plate's gaps are precisely calculated to ensure that the von Frey mechanical stimulation needle can pass freely through the mesh plate and accurately apply mechanical pressure to the mouse's feet without hindering its normal movement. This design ensures that the mouse can move naturally during experiments without being restricted by the mesh plate.

[0053] Three-degree-of-freedom robotic arm 3:

[0054] The three-degree-of-freedom robotic arm can move freely in the X, Y, and Z directions and is installed in the lower dark chamber of the integrated experimental box 6. This robotic arm uses a sophisticated electronic control system to control the movement and position of the von Frey mechanical stimulation needle 7, ensuring that the needle tip can accurately apply mechanical stimulation to the designated area on the sole of the mouse's foot. Through a preset program, the robotic arm can automatically adjust the position of the needle tip and the applied pressure, and in conjunction with a high-precision pressure sensor 8, ensure stable and controllable mechanical pressure, avoiding excessive pressure. At the same time, the flexibility of the robotic arm allows for multiple stimulations of different locations, increasing the flexibility and accuracy of the experiment.

[0055] Infrared cameras 4 and 5. Visible light camera 5:

[0056] The camera systems in the upper and lower experimental chambers consist of an infrared camera (4) and a visible light camera (5), respectively. The infrared camera, located in the lower dark chamber, focuses on detecting heat sources on the soles of the mice's feet, enabling monitoring of their thermal responses to mechanical stimuli in a dark environment. Simultaneously, the infrared camera, working in conjunction with a robotic arm and pressure sensors, can capture real-time temperature changes in the soles of the feet to aid in assessing pain responses. The visible light camera, installed in the upper transparent experimental chamber, records the overall posture changes of the mice. Combined with the mouse posture analysis and computing platform (9), the data captured by the cameras helps researchers assess the mice's responses and pain levels through posture changes.

[0057] The entire system achieves automated and precise testing of pain response in laboratory mice through the coordinated operation of a rigid opaque partition 1, a metal mesh plate 2, a three-degree-of-freedom robotic arm 3, a von Frey mechanical stimulation needle 7, an infrared camera 4, a visible light camera 5, a high-precision pressure sensor 8, and a mouse posture analysis and computing platform 9.

[0058] Working Principle: Mice or rats are initially placed on a metal mesh plate, separated by rigid, opaque partitions. The device runs for 30 minutes to desensitize the mice. Subsequently, a lower-layer infrared camera collects heat source information from the soles of the feet, and a mouse posture analysis platform locates the foot position. According to the pre-set experimental plan, the three-degree-of-freedom robotic arm of the von Frey mechanical stimulation needle moves to the mouse's foot position and applies the specified pain stimulus. An upper-layer visible light camera collects mouse posture information, and the mouse posture analysis platform analyzes the degree of pain response, thereby quantitatively analyzing the mouse's pain behavior or determining the analgesic effect of the analgesic drug. Finally, based on the objective analysis results, further reasonable experimental plans are implemented. This platform allows users to design experimental plans through an interactive interface and obtain experimental progress and data in real time.

[0059] This utility model achieves the above technical solution through the following means:

[0060] (1) Experimental preparation: First, place the experimental mice or rats on a metal grid plate and separate them with rigid, opaque partitions. The upper layer of the experimental chamber is transparent, allowing natural light to pass through, while the lower layer is designed as a dark chamber to prevent light from interfering with the infrared camera's detection and to avoid visual interference with the animals. Before the experiment, allow the animals to acclimatize to the laboratory and experimental chamber environment for 30 minutes and perform desensitization treatment on the mice. At the same time, run the equipment for 30 minutes in advance to ensure uniform experimental conditions.

[0061] (2) Infrared camera positioning: After the adaptation process is completed, the lower-level infrared camera is activated to collect heat source information from the mouse's paws. The collected data is analyzed by the mouse posture analysis and computing platform to accurately locate the mouse's paw position and ensure that the robotic arm can accurately position the von Frey mechanical stimulation needle to the target area.

[0062] (3) Robotic arm operation: Under the guidance of the mouse posture analysis and computing platform, the three-degree-of-freedom robotic arm moves to the foot of the mouse according to the preset experimental program and applies the specified mechanical pressure stimulus. The movement of the robotic arm and the pressure application process are completely controlled by the computer, avoiding errors caused by human operation.

[0063] (4) Upper-layer camera monitoring: The upper-layer visible light camera records the behavioral changes of the mice in real time throughout the experiment, including movement posture and pain response. The recorded data will be synchronously transmitted to the mouse posture analysis and computing platform for further behavioral analysis.

[0064] (5) Data Analysis and Feedback: Through machine learning algorithms, the device analyzes and models the collected experimental data to generate a quantitative pain index model. The experimental results are automatically stored and visualized, and researchers can access historical data for comparison and analysis at any time.

[0065] (6) Experiment Completion and Data Saving: After the experiment, all experimental data and analysis results will be automatically saved to the system database for convenient subsequent research analysis and data verification. The system also has an automatic experiment report generation function, reducing the workload of subsequent data processing.

[0066] In the description of this utility model, unless otherwise stated, "a plurality of" means two or more; the terms "upper," "lower," "left," "right," "inner," "outer," "front end," "rear end," "head," "tail," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, and are only for the convenience of describing this utility model and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of this utility model. In addition, the terms "first," "second," "third," etc., are used for descriptive purposes only and should not be construed as indicating or implying relative importance.

[0067] The above description is only a specific embodiment of this utility model, but the protection scope of this utility model is not limited thereto. Any modifications, equivalent substitutions and improvements made by those skilled in the art within the technical scope disclosed in this utility model, and within the spirit and principles of this utility model, should be included within the protection scope of this utility model.

Claims

1. A three-degree-of-freedom robotic arm-based automatic mouse von Frey pain measurement device, characterized in that, It includes an integrated experimental chamber, a three-degree-of-freedom robotic arm, a von Frey mechanical stimulation needle, a high-precision pressure sensor, a visible light camera, an infrared camera, and a mouse posture analysis and computing platform. The integrated experimental chamber has a metal mesh plate inside, which divides the integrated experimental chamber into upper and lower layers; the upper layer is a light-transmitting transparent experimental chamber, which is separated by a rigid opaque partition and is used to place experimental mice and is equipped with a visible light camera; the lower layer is an opaque dark chamber, which is equipped with a three-degree-of-freedom robotic arm and an infrared camera; the three-degree-of-freedom robotic arm is equipped with a von Frey mechanical stimulation needle, and a high-precision pressure sensor is installed at the von Frey mechanical stimulation needle.

2. The three-degree-of-freedom robotic arm automatic mouse von Frey pain measurement device as described in claim 1, characterized in that, A rigid, opaque partition is placed on a metal grid plate, allowing two rats to be tested simultaneously on the upper layer.

3. The three-degree-of-freedom robotic arm automatic mouse von Frey pain measurement device as described in claim 1, characterized in that, Two rigid, opaque partitions are placed vertically on a metal grid plate, allowing four mice to be tested simultaneously on the upper layer.

4. The three-degree-of-freedom robotic arm automatic mouse von Frey pain measurement device as described in claim 1, characterized in that, The three-degree-of-freedom robotic arm is driven by an electric servo motor to move the von Frey mechanical stimulation needle in the XYZ directions to different positions on the soles of the mouse's feet.

5. The three-degree-of-freedom robotic arm automatic mouse von Frey pain measurement device as described in claim 4, characterized in that, The movement range of the robotic arm in the XYZ directions is as follows: X direction 0-50cm, Y direction 0-50cm, Z direction 0-20cm.

6. The three-degree-of-freedom robotic arm automatic mouse von Frey pain measurement device as described in claim 1, characterized in that, High-precision pressure sensors adjust the maximum force, linear rate of change of force, magnitude of initial force, and duration of initial force for von Frey mechanical stimulation of the rat foot.

Images