Instantaneous traumatic spinal cord modeling system and method thereof

Abstract

The invention relates to the technical field of spinal cord trauma simulation, in particular to an instantaneous traumatic spinal cord modeling system and method, and the system comprises a mechanical arm, a clamp, an optical motion capture module and a control module; the clamp is installed at the driving end of the mechanical arm. An array type pressure sensor and a fiber grating force sensor are arranged on the clamp. The mechanical arm can drive the clamp to move and drive the clamp to be opened and closed, a piezoelectric-electromagnetic composite driver is arranged on the mechanical arm, the driving end of the piezoelectric-electromagnetic composite driver is connected with the driving end of the clamp, and the optical motion capture module is installed on the experimental platform and used for monitoring and calibrating the position and posture of the clamp on the mechanical arm relative to the spinal cord of a mouse. According to the scheme, the spinal cord forceps holder with millisecond-level response can be achieved, stability of various parameters in modeling can be guaranteed, a more rigorous and reliable research framework is formed, and experiment repeatability is higher.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of spinal cord injury simulation, and more particularly to a transient traumatic spinal cord modeling system and a method thereof. BACKGROUND

[0002] The spinal cord, as an important part of the central nervous system, not only accurately transmits the instructions from the brain to the limbs and organs, but also feeds back the sensory signals (such as pain, temperature, and pressure) of the skin and internal organs to the brain in real time, thus building a seamless connection between internal and external information. Moreover, the spinal cord can independently complete some rapid reflex actions and participate in the regulation of the functions of internal organs. When a transient blunt or penetrating injury such as a traffic accident, a fall from a height, and a violent blow occurs, it may cause traumatic spinal cord injury (TSCI). Traumatic spinal cord injury often leads to irreversible sensory and motor dysfunction, accompanied by abnormal reflex activity and autonomic nervous dysfunction, and is the main cause of early disability.

[0003] In order to further understand traumatic spinal cord injury and implement treatment, the existing technology mainly uses mouse models to conduct basic research on traumatic spinal cord injury. This is because the mouse genes are highly homologous to humans, the mouse has a fast breeding speed, low cost, and convenient operation, and has the advantages of small ethical controversy and high-throughput research adaptation. Therefore, the current method mainly simulates the clinically common traumatic spinal cord injury by physically damaging the mouse, and further understands the traumatic spinal cord injury according to the injury and treatment of the animal. The physical damage method of the mouse mainly includes heavy object impact, forceps clamping, balloon compression, spinal cord displacement, spinal cord transection, explosion simulator, hydraulic impact, high-speed rotation device, transverse stretching device, high-frequency vibration table, etc.

[0004] Among the above-mentioned mouse traumatic spinal cord injury simulation methods, forceps clamping has the advantages of convenient operation, high matching degree with clinical pathological characteristics, and strong device expandability, and is therefore widely used in mouse spinal cord injury simulation experiments. However, when forceps clamping is used to mechanically damage the mouse at present, most of the forceps clamping is semi-automatic or manually controlled. Since the action of the forceps clamping is slow, it is difficult to simulate the traumatic spinal cord injury caused by instantaneous violence, and the clamping force, time, position, and other parameters in repeated experiments are difficult to keep consistent, which has certain defects in the rigor and repeatability of the research results. SUMMARY

[0005] The purpose of the present application is to overcome the deficiencies in the prior art that it is difficult to simulate the traumatic spinal cord injury caused by instantaneous violence when using forceps to simulate traumatic spinal cord injury in mice, and it is difficult to keep the parameters such as force, time and position consistent in repeated experiments, and to provide a kind of instantaneous traumatic spinal cord modeling system and method, which can realize millisecond level response of spinal cord forceps, and can also ensure the stability of various parameters in modeling, form a more rigorous and reliable research framework and have higher experimental repeatability.

[0006] To solve the above technical problems, the technical scheme adopted by the present application is: Provided is a kind of instantaneous traumatic spinal cord modeling system, including mechanical arm, clamp, optical motion capture module and control module; The clamp is installed on the driving end of the mechanical arm, at least one clamping surface of the clamp is provided with an array type pressure sensor, and the tip of at least one clamping surface of the clamp is provided with a fiber optic grating force sensor; The mechanical arm can drive the clamp to move and drive the clamp to open and close, and a piezoelectric-electromagnetic composite driver is arranged on the mechanical arm, and the driving end of the piezoelectric-electromagnetic composite driver is connected with the driving end of the clamp: The optical motion capture module is installed on the experimental platform to monitor and calibrate the position and posture of the clamp on the mechanical arm relative to the mouse spinal cord; The control module is connected with the mechanical arm, the piezoelectric-electromagnetic composite driver, the array type pressure sensor, the fiber optic grating force sensor and the optical motion capture module.

[0007] In the present application, the mechanical arm is a commercial six-axis industrial or medical robot arm, such as KUKA LBR Med or similar equipment. Its main function is to realize the macro positioning of the clamp in three-dimensional space, and it can move the clamp to the target segment of the mouse spinal cord (such as the thoracic vertebrae T9-T10 area) with sub-millimeter accuracy. The robot arm can be connected with the control module through data line to receive and execute the pose instructions from the high level.

[0008] The two clamping surfaces of the clamp are parallel to each other, and the two clamping surfaces of the clamp are provided with array type pressure sensors, and the tips of the two clamping surfaces of the clamp are provided with fiber optic grating force sensors. One half of the clamp is fixed on the mechanical arm, and the other half can slide on the mechanical arm in the direction of approaching or away from the half of the clamp fixed on the mechanical arm through the driving of the piezoelectric-electromagnetic composite driver.

[0009] The piezoelectric-electromagnetic composite driver includes a piezoelectric driver and an electromagnetic driver, both of which are connected to the control module to receive and execute the action commands from the controller. The piezoelectric driver is composed of one or more stacked piezoelectric ceramic rings (e.g., Noliac NAC2125). The piezoelectric effect enables it to produce a tiny but extremely fast (response time <1 ms) deformation when a voltage is applied. The piezoelectric ceramic ring has extremely high stiffness and huge output force (block force up to 8450 N), responsible for performing the final, precisely controlled, millisecond-level clamping action after the jaws contact the tissue. The electromagnetic driver is composed of a miniature electromagnetic coil (e.g., Boulder Nonlinear BLM-120). The electromagnetic driver drives a armature through electromagnetic force to achieve a larger stroke (millimeter level) movement, responsible for the macroscopic opening and closing of the jaws before and after the clamping action, bringing the piezoelectric driver into its effective working range before performing the clamping action through the piezoelectric driver.

[0010] The arrayed pressure sensor is a piece of flexible MEMS pressure sensing film (e.g., Tekscan 5051) laminated on the inner surface of the clamping tool in contact with the spinal cord tissue. The sensor contains an array composed of multiple independent sensing units (senses), with a spatial resolution of up to 62 sensing units per square centimeter, capable of capturing the spatial distribution of clamping force on the surface of the spinal cord in real time, thereby evaluating the uniformity of pressure and avoiding unintended damage caused by local pressure concentration.

[0011] The fiber Bragg grating force sensor integrates one or more FBG elements (e.g., Luna os1100). When a force is applied, the strain of the optical fiber causes the Bragg wavelength to shift, which can be detected by a high-speed FBG demodulator (sampling rate ≥100 kHz), and the instantaneous total clamping force can be converted, with a measurement accuracy of millinewton (mN) level.

[0012] The optical motion capture module is a motion capture camera, such as OptiTrack PrimeX 41, which can achieve absolute three-dimensional positioning of the mechanical arm and the clamp, and correct the position error of the mechanical arm and the clamp.

[0013] The control module can control the mechanical arm, the piezoelectric-electromagnetic composite driver, the arrayed pressure sensor, the fiber Bragg grating force sensor, and the optical motion capture module to work, and can also plan the motion path of the mechanical arm and the clamp, process the data from the piezoelectric-electromagnetic composite driver, the arrayed pressure sensor, the fiber Bragg grating force sensor, and the optical motion capture module, and adjust the motion path of the mechanical arm and the clamp according to the data, and judge whether the traumatic spinal cord modeling of the mouse is successfully completed.

[0014] The instant traumatic spinal cord modeling system introduces a millisecond piezoelectric-electromagnetic composite driver as a high dynamic actuator and integrates mechanics and displacement sensors therein, can collect relevant parameters in real time and control the whole system to work through the control module, and fundamentally solves the individual difference problem caused by manual operation.

[0015] Preferably, a high-speed camera mounted on the experimental platform is further included, which is used to record the process of clamping the mouse spinal cord, and the high-speed camera is connected with the control module. The high-speed camera, such as Photron FASTCAM Nova, can record the clamping process at a rate of not less than 10,000 frames per second. The high-speed camera has a dual function: first, as an independent verification tool, by analyzing the image frame by frame, the actual duration of the contact between the jaw and the spinal cord can be accurately calculated, which is used for comparison with the electronic instruction time; second, combined with technologies such as laser speckle interferometry, it can be used to non-contact measure the full-field strain distribution of the tissue surface, providing more abundant tissue deformation information for the control system.

[0016] Preferably, a displacement sensor mounted on the driving end of the mechanical arm is further included, which can measure the opening displacement of the clamp, and the displacement sensor is connected with the control module. The displacement sensor is a high-precision displacement encoder, such as a linear optical encoder of Renishaw VIONiC series, which can directly measure the linear movement distance after being mechanically coupled to the jaw of the clamp. This direct linear displacement measurement eliminates all assumptions and errors about the transmission mechanism, providing real ground position feedback with a resolution of up to 50 nanometers.

[0017] The application further provides an instant traumatic spinal cord modeling method for the instant traumatic spinal cord modeling system, which comprises the following steps: Step one: according to the experimental target, the mouse is prepared for surgery and the motion route of the mechanical arm and the clamp is planned; Step two: the control module drives the mechanical arm to move the clamp along the motion route planned in step one to the target spinal cord segment of the animal and keeps the clamp in an open-jaw posture, and the position and posture of the mechanical arm and the clamp are calibrated and confirmed by the optical motion capture module; Step three: the control module issues an instant control command to make the piezoelectric-electromagnetic composite driver drive the jaw of the clamp to clamp the target spinal cord segment of the animal, and the working of the piezoelectric-electromagnetic composite driver is adjusted according to the data stream from the piezoelectric-electromagnetic composite driver, the fiber Bragg grating force sensor, the high-speed camera and the displacement sensor until the millisecond precise clamping injury of the spinal cord is completed; Step four: the consistency of the spinal cord injury of the mouse is verified.

[0018] The instant traumatic spinal cord modeling method of the application can not only ensure the stability of various parameters in the modeling process, but also eliminate individuals with offset modeling results through damage consistency evaluation, further ensuring the standardization of the modeling method, forming a more rigorous and reliable research framework, filling the gap in the field of TSCI modeling caused by instant violence, and laying a solid foundation for the research of pathophysiological process, molecular mechanism and development of treatment methods of TSCI.

[0019] Preferably, in the step three, the data stream comprises jaw real-time pressure distribution data from the piezoelectric-electromagnetic composite driver, jaw instantaneous clamping force data from the fiber bragg grating force sensor, jaw and spinal cord contact time data from the high-speed camera, and jaw opening and closing displacement data from the displacement sensor. The jaw and spinal cord contact time data from the high-speed camera is obtained by the following steps: After the high-speed camera obtains the image set of the process of clamping the spinal cord by the jaw, the contact time of the jaw and the spinal cord is calculated according to the number of the image of the contact between the jaw and the spinal cord, the number of the image of the separation between the jaw and the spinal cord in the image set, and the frame rate of the high-speed camera.

[0020] Preferably, in the step three, the working of the piezoelectric-electromagnetic composite driver is adjusted according to the following steps: S31: obtaining data stream; S32: processing the data stream to obtain jaw pressure distribution data, jaw instantaneous clamping force data, jaw opening and closing displacement data, and jaw and spinal cord contact time when the clamp jaw is closed, and judging whether the data meets the experimental target. If it meets the experimental target, S33 is performed; if it does not meet the experimental target, S34 is performed; S33: controlling the clamp and the mechanical arm according to the preset experimental route; S34: performing S31 to process the data stream, and judging whether the clamp contacts the spinal cord. If it contacts, S35 is performed; if it does not contact, S36 is performed; S35: performing step one and replacing the mouse; S36: performing step one and re-planning the motion route of the mechanical arm and the clamp.

[0021] In the technical solution, the surgical preparation and planning of the movement route of the mouse in step one includes: injecting 1.25% alverine (Sigma-Aldrich, T48402) into the abdominal cavity of the mouse at 20 μl / g for anesthesia. Then, the skin on the back of the mouse at the spinal cord is prepared, the skin is incised, the laminectomy is performed, the lamina of about 1 mm at T9-T10 is removed, the forceps is manually inserted into the lamina gap, and attention is paid not to injure the spinal cord. After the insertion, the forceps head end is stopped until it touches the hard spine, and the relative position of the forceps and the mouse is maintained unchanged. The movement route of the mechanical arm and the clamp includes: establishing a three-dimensional coordinate system through an optical motion capture module, determining the positions of the mechanical arm, the clamp and the mouse spinal cord in the three-dimensional coordinate system, and then planning the movement route of the mechanical arm and the clamp according to the relative positions of the mouse spinal cord, the mechanical arm and the clamp.

[0022] The calibration and confirmation of the position and posture of the mechanical arm and the clamp in step two include: after the mechanical arm drives the clamp to move along the planned route, the optical motion capture module repositions the mechanical arm and the clamp in the three-dimensional coordinate system, and determines whether the position coordinates of the repositioning are consistent with the preset coordinates after the movement along the preset movement route. If consistent, the calibration is ended; if not consistent, the route is re-planned to drive the mechanical arm and the clamp to move and calibrate until the position coordinates of the mechanical arm and the clamp are consistent with the preset coordinates.

[0023] In steps three and four, the control module adjusts the working of the piezoelectric-electromagnetic composite driver, which includes the following levels: The first level is a synchronous data acquisition layer. The data flow is strictly synchronized by a hardware trigger signal to ensure that the timestamp jitter of all data is less than 1 millisecond. This provides a highly consistent data basis in time for subsequent data fusion and state estimation.

[0024] The second level is an LSTM-based state estimation and fusion layer. The original multi-channel sensor data has high dimensionality, contains noise and has complex time-dependent characteristics, which is difficult to directly use for control decision. Therefore, the present application introduces a long short-term memory (LSTM) network as the core engine of data fusion and state estimation. The LSTM network is trained offline to learn the complex nonlinear mapping from high-dimensional, synchronized sensor time series data (input) to low-dimensional “state vector” (output) that describes the current biomechanical state of the organization.

[0025] The essence of the second layer is a small neural network model, which aims to process the jaw real-time pressure distribution data from the piezoelectric-electromagnetic composite driver, the jaw instantaneous clamping force data from the fiber Bragg grating force sensor, the jaw contact time data with the spinal cord from the high-speed camera, and the jaw opening and closing displacement data from the displacement sensor. The instantaneous data at the same time is converted into a time vector, and the spinal cord clamping state is represented by the time vector.

[0026] Third level: PID adaptive adjustment layer based on fuzzy logic: Although the traditional PID controller has fast response speed, its fixed gain parameters (K_p, K_i, K_d) cannot adapt to nonlinear and time-varying controlled objects, so this scheme uses a fuzzy inference system (Fuzzy Inference System, FIS) to adjust the PID gain in real time and intelligently, thereby realizing adaptive control.

[0027] Innovative input: Unlike traditional double-input (error e and error rate \dot{e}) fuzzy PID controllers, the FIS of this invention is a three-input system. In addition to e and \dot{e}, it also receives a state vector U_{t} (or its key components, such as the estimated tissue stiffness k_{\text{tissue}}$) from the second layer LSTM network output as the third input.

[0028] Fuzzy rule base: FIS contains a set of "IF-THEN" rules based on expert knowledge and experimental data. These rules map the fuzzy states of input variables (such as "error is large and positive", "error rate is negative", "tissue stiffness is high") to the fuzzy output of PID gain adjustment (\Delta K_p, \Delta K_i, \Delta K_d).

[0029] Example rule: As shown in Table 1, a specific rule may be: "If the error is large and positive (i.e. the actual force is much smaller than the target force) and the estimated tissue stiffness is high, then increase the proportional gain K_p significantly to produce a stronger initial response". This control logic combined with tissue state allows the controller to make more intelligent decisions than traditional PID.

[0030]

[0031] Table 1 - A logical rule of the fuzzy logic rule base The purpose of the third level is to plan and execute the motion of the robot arm and the clamp, and the closing action of the clamp jaw according to the data stream, and to determine whether the molding is successful according to the spinal cord clamping information in the data stream.

[0032] Fourth layer: bottom motion execution layer: After the third layer of intelligent adjustment, the PID controller with optimal time-varying gain calculates the final control command (e.g., voltage applied to the piezoelectric driver) according to the current error to drive the end effector to accurately track the pre-set force-time or displacement-time trajectory, thereby completing the millisecond-level precise pinch injury.

[0033] Preferably, in the step four, the consistency of spinal cord injury of the mouse is verified by one or more steps as follows: S41: Real-time biomechanical verification: process the data in the data stream and determine whether the data is within the error range of the spinal cord injury modeling experimental design. If yes, the injury is consistent; if no, the injury is not consistent. In this step: whether the instantaneous trauma is completed or not is determined according to the following formula.

[0034] 1. Actual Injury Duration calculation formula: [T_{\text{actual}}=T_{\text{pull-off}}-T_{\text{contact}}] Wherein: (T_{\text{pull-off}}) represents the image frame timestamp when the forceps is pulled away from the spinal cord. (T_{\text{contact}}) represents the image frame timestamp when the forceps first touches the spinal cord.

[0035] 2. Expected Injury Duration calculation formula: [T_{\text{expected}}=T_{\text{motor-command}}^{\text{e}}-T_{\text{motor-command}}^{\text{p}}] Wherein: (T_{\text{motor-command}}^{\text{e}}) represents the command sending time of the pull motor.

[0036] (T_{\text{motor-command}}^{\text{p}}) represents the command sending time of the piezoelectric motor.

[0037] 3. Judgment criteria: Condition 1 (Condition 1): [\DeltaT=T_{\text{actual}}-T_{\text{expected}}<\text{Threshold}_1] Wherein, the threshold value (Threshold_1) should be set within 10 milliseconds (ms).

[0038] Condition two (Condition2): The force-time curve meets the following conditions: [F_{\text{min}}>\text{Threshold}2] Wherein, (F{\text{min}}) is the minimum value of the force sensor reading within the actual trauma time, and the threshold value (Threshold_2) should be set above 200 millinewtons (mN).

[0039] 4. Judgment result: The case of simultaneously meeting the above two conditions is regarded as the instantaneous trauma being successfully completed. If the mouse spinal cord injury model does not meet the above judgment standard, it is determined that the model construction fails, and the mouse will not enter this experiment.

[0040] S42: Postoperative functional evaluation: long-term behavioral tracking is performed on mice that meet the modeling target to evaluate the damage and recovery of their neural function; In this step: Basso Mouse Scale (BMS) score is used: this is the gold standard for evaluating the motor function of mouse hind limbs. On the 1st, 3rd, 7th, 14th, 21st, and 28th day after injury, two observers who are unaware of the grouping observe the autonomous movement of mice in an open field and score them according to the BMS scoring standard (0 points represent complete paralysis, and 9 points represent normal movement).

[0041] Gait analysis: in the later stage after injury (such as the 28th day), the hind limbs of mice are dipped in different colors of non-toxic pigments, and they are allowed to walk on white paper. By analyzing the footprints left, parameters such as step length, step width, and hind limb coordination are quantified to more finely evaluate the gait recovery.

[0042] S43: Quantitative histopathological analysis: after the spinal cord tissue of the spinal cord injury modeling mouse is made into a section, it is stained and analyzed to evaluate the collagen deposition and nerve damage in the spinal cord injury area.

[0043] In this step: At the end of the experiment (such as the 14th day or 28th day), the mice are euthanized and the spinal cord tissue is obtained for detailed microscopic structure analysis.

[0044] Spinal cord tissue acquisition and section acquisition: After the mice are anesthetized at a specific time, they are perfused with normal saline and a 4% paraformaldehyde (PFA) solution in sequence. After completing the perfusion, the skin on the back is cut with surgical scissors, the dorsal erector spinae muscle and the lamina near the sampling site (about T6 to T12) are removed to expose the spinal cord; the spinal cord is cut about 2 segments before and after the sampling site with a surgical knife, and the nerve roots around the spinal cord are carefully separated and cut with microscissors, then the spinal cord tissue sample is carefully taken out with tweezers and soaked in 4% PFA for dark storage, waiting for further experiments. Fresh spinal cord tissue is fixed by soaking in a 4% PFA solution for 24 hours. After 24 hours of fixation, the tissue is transferred to a 30% sucrose solution for dehydration. After 24 to 48 hours of tissue dehydration, the tissue is observed to sink to the bottom, and the dehydration is completed. The tissue is taken out and the surface liquid is wiped off with a water-absorbing paper, and the spinal cord tissue is fully embedded with an optimal cutting temperature (OCT) embedding agent and placed in a -20°C refrigerator for freezing and solidification. Start the freezing microtome in advance, and set the operating room temperature to -22°C and the fixation table temperature to -17°C. The tissue is taken out of the mold and fixed on the microtome knife head. Set the section thickness to 40 μm, and cut along the coronal plane of the spinal cord. After cutting to the parenchymal tissue, continue to spin for 12 to 13 times to reach the 1 / 3 position of the sagittal plane of the spinal cord; set the section thickness to 10 to 12 μm, and cut continuously along the coronal plane of the spinal cord.

[0045] Histopathological analysis of tissue sections: After the mice are euthanized at 14 days post-injury, they are perfused with normal saline and a 4% PFA solution, and then the spinal cord tissue is sectioned and analyzed by H&E, Masson, and Nissl staining to evaluate collagen deposition and nerve damage in the injured area.

[0046] Hematoxylin-eosin (H&E) staining: used to observe the overall cell structure, inflammatory cell infiltration, and cavity formation in the injured area.

[0047] Nissl staining: used to show neuron cell bodies (Nissl bodies) and evaluate the survival and death of neurons.

[0048] Masson's trichrome staining: used to show collagen fibers and evaluate the formation of fibrosis and scar tissue after injury.

[0049] Luxol fast blue (LFB) staining: specifically stains myelin sheaths and is used to evaluate demyelination and remyelination in the white matter area.

[0050] Immunofluorescence staining: uses specific antibodies to label key cells and structures, such as GFAP (glial fibrillary acidic protein, which labels reactive astrocytes), Iba1 (which labels microglia / macrophages), and NF200 (neurofilament protein, which labels axons).

[0051] Quantitative analysis: The stained sections are quantitatively measured by using image analysis software (such as ImageJ). Key indicators include: the hollow volume of the damage center area, the total lesion volume, and the most critical residual white matter area percentage. The residual white matter area is one of the most important histological indicators for predicting functional recovery. By accurately quantifying this indicator, the comparability of results between different experimental groups and different studies can be greatly improved.

[0052] Preferably, after the end of the third step, the mouse is hemostatic and sutured, the mouse body temperature is maintained stable using a heating pad until it wakes up, and physiological saline is subcutaneously given to the mouse for rehydration and analgesics are given to the mouse for pain relief according to the condition of the mouse. The model mouse is nursed in daily feeding, such as urination.

[0053] Preferably, after the end of the fourth step, the mechanical data and displacement data of the clamp are recorded and processed to verify the repeatability of the experiment.

[0054] In the spinal cord clamp injury experiment, the mechanical data and displacement change need to be recorded synchronously to evaluate the operation accuracy and injury consistency. The clamping force (mN level) and pressure distribution (kPa) are monitored in real time by high-precision force sensors, combined with displacement encoders (μm level resolution) and optical motion capture systems to collect the opening and closing displacement of the clamp and three-dimensional motion trajectory, to ensure that the mechanical load and tissue deformation meet the preset parameters (such as clamp force 10-15 mN, displacement 500±50 μm). All data are synchronized by hardware trigger (error <1 ms), filtered and feature extracted, and then the force-displacement curve characteristics are analyzed, the inter-experiment repeatability is verified by the coefficient of variation (CV <10%), and finally the mechanical parameters are associated with postoperative histological results to provide quantitative basis for injury model standardization.

[0055] The sensor needs to be calibrated before the experiment and the safety threshold (such as force >20 mN automatically terminated) is set, the force / displacement fluctuation is monitored in real time during the operation, and the injury degree is quantified by the area under the force-displacement curve and other indicators after the operation. This systematic recording method can effectively control the mechanical arm operation error (displacement lag <50 μm), ensure the consistency of the injury in different batches of experiments, and establish a reliable mechanical basis for subsequent histological analysis.

[0056] Compared with the prior art, the beneficial effects of the present application are: The millisecond piezoelectric-electromagnetic composite driver is introduced as a high dynamic actuator in the transient traumatic spinal cord modeling system of the present application, and the mechanical and displacement sensors are integrated therein, which can collect relevant parameters in real time and control the whole system to work through the control module, thereby fundamentally solving the individual difference problem caused by manual operation.

[0057] The instant traumatic spinal cord modeling method can ensure the stability of various parameters in the modeling process, and through damage consistency evaluation, can eliminate individuals with offset modeling results, further ensure the standardization of the modeling method, form a more rigorous and reliable research framework, make up for the blank in the field of TSCI modeling caused by instant violence, and lay a solid foundation for the research and development of treatment methods in the direction of pathophysiological process and molecular mechanism of TSCI. BRIEF DESCRIPTION OF DRAWINGS

[0058] Figure 1 It is a structural schematic diagram of a transient traumatic spinal cord modeling system; Figure 2 It is a structural schematic diagram of a clamp of a transient traumatic spinal cord modeling system; Figure 3 It is an enlarged view of A of Figure 2 Figure 4 It is a flowchart of a transient traumatic spinal cord modeling method.

[0059] 1, mechanical arm; 2, clamp; 3, array type pressure sensor; 4, fiber Bragg grating force sensor; 5, piezoelectric-electromagnetic composite driver; 6, high-speed camera. DETAILED DESCRIPTION

[0060] The drawings are only used for illustrative description, and cannot be understood as a limitation on the patent; in order to better illustrate the embodiment, some components in the drawings may be omitted, enlarged or reduced, and do not represent the size of the actual product; for those skilled in the art, it is understandable that some well-known structures and their descriptions in the drawings may be omitted. The positional relationship described in the drawings is only used for illustrative description, and cannot be understood as a limitation on the patent.

[0061] The same or similar reference numerals in the drawings of the embodiments of the present application correspond to the same or similar components; in the description of the present application, it should be understood that if the terms "upper", "lower", "left", "right", "long" and "short" indicate the orientation or positional relationship, it is based on the orientation or positional relationship shown in the drawings, and is only for the convenience of describing the present application and simplifying the description, and does not indicate or imply that the device or element referred to must have a particular orientation, be constructed and operated in a particular orientation, therefore, the terms describing the positional relationship in the drawings are only used for illustrative description, and cannot be understood as a limitation on the patent, and for those skilled in the art, the specific meaning of the above terms can be understood according to the specific situation.

[0062] The technical solutions of the present application will be further specifically described below through specific embodiments and in combination with the drawings: Embodiment one This embodiment is the first embodiment of a transient traumatic spinal cord modeling system, as shown in​Figures 1-3 as shown, including a mechanical arm 1, a clamp 2, an optical motion capture module, and a control module; The clamp 2 is installed on the driving end of the mechanical arm 1, and at least one clamping surface of the clamp 2 is provided with an array pressure sensor 3, and the tip of at least one clamping surface of the clamp 2 is provided with a fiber Bragg grating force sensor 4. The mechanical arm 1 can drive the clamp 2 to move and drive the clamp 2 to open and close, and a piezoelectric-electromagnetic composite driver 5 is arranged on the mechanical arm 1, and the driving end of the piezoelectric-electromagnetic composite driver 5 is connected with the driving end of the clamp 2: The optical motion capture module is installed on the experimental platform to monitor and calibrate the position and attitude of the clamp 2 on the mechanical arm 1 relative to the mouse spinal cord; The control module is connected with the mechanical arm 1, the piezoelectric-electromagnetic composite driver 5, the array pressure sensor 3, the fiber Bragg grating force sensor 4, and the optical motion capture module.

[0063] Specifically, the mechanical arm 1 is a commercial six-axis industrial or medical robot arm, such as KUKA LBR Med or similar equipment. Its main function is to realize the macro positioning of the clamp 2 in three-dimensional space, and can move the clamp to the target segment (such as the thoracic vertebrae T9-T10 area) of the mouse spinal cord with sub-millimeter accuracy. The robot arm can be connected with the control module through a data line to receive and execute the pose instructions from the high-level.

[0064] The two clamping surfaces of the clamp 2 are parallel to each other, and the two clamping surfaces of the clamp 2 are provided with array pressure sensors 3, and the tips of the two clamping surfaces of the clamp 2 are provided with fiber Bragg grating force sensors 4.

[0065] The piezoelectric-electromagnetic composite driver 5 includes a piezoelectric driver and an electromagnetic driver, both of which are connected with the control module to receive and execute the action commands from the controller. The piezoelectric driver is composed of one or more stacked piezoelectric ceramic rings (for example, Noliac NAC2125). The piezoelectric effect enables it to produce a small but extremely fast (response time <1ms) deformation when a voltage is applied. The piezoelectric ceramic ring has extremely high stiffness and huge output force (block force up to 8450 N), responsible for performing the final, precise, millisecond-level clamp action after the clamp contacts the tissue. The electromagnetic driver is composed of a miniature electromagnetic coil (for example, similar to Boulder Nonlinear BLM-120). The electromagnetic driver drives an armature through electromagnetic force to realize a larger stroke (millimeter level) movement, responsible for the macro opening and closing of the clamp before and after the clamp action, bringing the piezoelectric driver into its effective working range and then executing the clamping action of the clamp 2 through the piezoelectric driver.

[0066] Arrayed pressure sensor 3 is a piece of flexible MEMS pressure sensor film (such as Tekscan 5051) laminated to the inner surface of the forceps in contact with the spinal cord tissue. The sensor contains an array composed of multiple independent sensing units (senses), with a spatial resolution of up to 62 sensing units per square centimeter, capable of capturing the spatial distribution of the force on the surface of the spinal cord in real time, thereby evaluating the uniformity of the pressure and avoiding unintended damage caused by local pressure concentration.

[0067] Fiber Bragg grating force sensor 4 integrates one or more FBG elements (such as Luna os1100). When a force is applied, the strain of the optical fiber causes the Bragg wavelength to shift, which is detected by a high-speed FBG demodulator (sampling rate ≥ 100 kHz), which can be converted into the instantaneous total force of the forceps, with a measurement accuracy of millinewton (mN) level.

[0068] Optical motion capture module is a motion capture camera, such as OptiTrack PrimeX 41, which can achieve absolute three-dimensional positioning of mechanical arm 1 and forceps 2, and correct the position error of mechanical arm 1 and forceps 2.

[0069] The control module can control the operation of the mechanical arm 1, the piezoelectric-electromagnetic composite driver 5, the arrayed pressure sensor 3, the fiber Bragg grating force sensor 4 and the optical motion capture module, and can also plan the motion path of the mechanical arm 1 and the forceps 2, process the data from the piezoelectric-electromagnetic composite driver 5, the arrayed pressure sensor 3, the fiber Bragg grating force sensor 4 and the optical motion capture module, and adjust the motion path of the mechanical arm 1 and the forceps 2 according to the data, and judge whether the traumatic spinal cord modeling of the mouse is successfully completed.

[0070] The beneficial effects of the embodiment are as follows: The instantaneous traumatic spinal cord modeling system of the embodiment introduces a millisecond-level piezoelectric-electromagnetic composite driver 5 as a high-dynamic actuator and integrates mechanical and displacement sensors therein, which can collect relevant parameters in real time and control the entire system to work through the control module, thereby fundamentally solving the individual difference problem caused by manual operation.

[0071] Embodiment two The second embodiment of the instantaneous traumatic spinal cord modeling system, the embodiment further limits the structure based on the first embodiment.

[0072] Specifically, it further includes a high-speed camera 6 installed on the experimental platform, which is used to record the process of the clamp 2 clamping the mouse spinal cord, and the high-speed camera 6 is connected with the control module. The high-speed camera 6 is a Photron FASTCAM Nova, which can record the clamping process at a rate of not less than 10,000 frames per second.

[0073] Specifically, it further includes a displacement sensor installed on the driving end of the mechanical arm 1, which can measure the opening displacement of the clamp 2, and the displacement sensor is connected with the control module. The displacement sensor is a high-precision displacement encoder, such as a linear optical encoder of the Renishaw VIONiC series, which can directly measure the linear movement distance after being mechanically coupled to the jaw of the clamp.

[0074] The beneficial effects of the embodiment are as follows: The high-speed camera 6 has a dual function: first, as an independent verification tool, by analyzing the image frame by frame, the actual duration of the contact between the jaw and the spinal cord can be accurately calculated, which is used for comparison with the electronic command time; second, combined with laser speckle interferometry and other technologies, it can be used to non-contact measure the full-field strain distribution of the tissue surface, providing more abundant tissue deformation information for the control system. The displacement sensor can directly measure the linear movement distance. This direct linear displacement measurement eliminates all assumptions and errors about the transmission mechanism, providing ground truth position feedback with a resolution of up to 50 nanometers.

[0075] Embodiment three The embodiment is an embodiment of a method for modeling a transient traumatic spinal cord, which is used for a transient traumatic spinal cord modeling system as in embodiment two, such as Figure 4 As shown, it includes the following steps: Step one: according to the experimental target, the mouse is prepared for surgery and the motion route of the mechanical arm 1 and the clamp 2 is planned; Step two: the control module drives the mechanical arm 1 to move the clamp 2 along the motion route planned in step one to the target spinal cord segment of the animal and makes the clamp 2 keep the open posture, and the position and posture of the mechanical arm 1 and the clamp 2 are calibrated and confirmed by the optical motion capture module; Step three: the control module issues a transient control command to make the piezoelectric-electromagnetic composite driver 5 drive the jaw of the clamp 2 to close and clamp the target spinal cord segment of the animal, and adjust the work of the piezoelectric-electromagnetic composite driver 5 according to the data stream from the piezoelectric-battery composite driver, the fiber Bragg grating force sensor 4, the high-speed camera 6 and the displacement sensor until the millisecond-level precise clamping injury of the spinal cord is completed; Step four: verify the consistency of the spinal cord injury of the mouse.

[0076] Specifically, the surgical preparation and the planning of the movement route of the mouse include: injecting 1.25% alverine (Sigma-Aldrich, T48402) into the abdominal cavity of the mouse at 20 μl / g for anesthesia. Then, the back skin of the mouse at the spinal cord is prepared, the skin is incised, the laminectomy is performed, the lamina of about 1 mm long at T9-T10 is removed, the forceps is manually inserted into the lamina gap, and attention is paid not to injure the spinal cord. After the insertion, the forceps head end is stopped until it touches the hard spine, and the relative position of the forceps and the mouse is maintained unchanged. The movement route of the mechanical arm 1 and the clamp 2 includes: establishing a three-dimensional coordinate system through an optical motion capture module, determining the positions of the mechanical arm 1, the clamp 2 and the mouse spinal cord in the three-dimensional coordinate system, and then planning the movement route of the mechanical arm 1 and the clamp 2 according to the relative positions of the mouse spinal cord and the mechanical arm 1 and the clamp 2.

[0077] Specifically, the calibration and confirmation of the position and attitude of the mechanical arm 1 and the clamp 2 include: after the movement of the mechanical arm 1 driving the clamp 2 along the planned route is completed, the optical motion capture module repositions the mechanical arm 1 and the clamp 2 in the three-dimensional coordinate system, and determines whether the repositioned position coordinates of the mechanical arm 1 and the clamp 2 are consistent with the preset coordinates after the movement along the preset movement route is completed. If consistent, the calibration is ended; if not consistent, the route is re-planned to drive the mechanical arm 1 and the clamp 2 to move and calibrate until the position coordinates of the mechanical arm 1 and the clamp 2 are consistent with the preset coordinates.

[0078] Specifically, in the step three, the data stream includes the real-time pressure distribution data of the clamp from the piezoelectric-electromagnetic composite driver 5, the instantaneous clamping force data of the clamp from the fiber Bragg grating force sensor 4, the contact time data of the clamp and the spinal cord from the high-speed camera 6, and the opening and closing displacement data of the clamp from the displacement sensor. The contact time data of the clamp and the spinal cord from the high-speed camera 6 is obtained by the following steps: After the high-speed camera 6 obtains the image set of the process of the clamp clamping the spinal cord, the contact time of the clamp and the spinal cord is calculated according to the number of the images of the contact of the clamp and the spinal cord, the number of the images of the separation of the clamp and the spinal cord, and the frame rate of the high-speed camera 6.

[0079] Specifically, in the step three, the working of the piezoelectric-electromagnetic composite driver 5 is adjusted according to the following steps: S31: obtaining the data stream; S32: processing the data stream to obtain the clamp pressure distribution data, the clamp instantaneous clamping force data, the clamp opening and closing displacement data, and the contact time of the clamp and the spinal cord when the clamp is closed, and judging whether the data meets the experimental target. If it meets the experimental target, S33 is performed; if it does not meet the experimental target, S34 is performed; S33: controlling the clamp and the mechanical arm to work according to the preset experimental route; S34: performing S31, processing the data stream, judging whether the clamp contacts the spinal cord, if yes, performing S35; if not, performing S36; S35: performing step one and replacing the mouse; S36: performing step one and re-planning the motion route of the robot arm and the clamp.

[0080] The beneficial effects of the embodiment are as follows: The transient traumatic spinal cord modeling method of the embodiment can not only ensure the stability of various parameters in the modeling process, but also eliminate individuals with offset in the modeling results through damage consistency evaluation, further ensuring the standardization of the modeling method, forming a more rigorous and reliable research framework, making up for the blank in the field of TSCI modeling caused by transient violence, and laying a solid foundation for the research on the pathophysiological process and molecular mechanism of TSCI and the development of treatment methods.

[0081] In the specific contents of the above specific embodiments, each technical feature can be combined arbitrarily without contradiction. In order to make the description simple, all possible combinations of the above technical features are not described, but as long as the combination of the technical features does not exist contradiction, it should be considered as the scope of the present disclosure.

[0082] Obviously, the above embodiments of the present application are only examples for clearly illustrating the present application, and are not intended to limit the implementation modes of the present application. Based on the above description, other different forms of changes or variations can be made by those skilled in the art. Here, it is not necessary and impossible to exhaust all the implementation modes. Any modification, equivalent replacement and improvement made within the spirit and principle of the present application shall be included in the protection scope of the claims of the present application.

Claims

1. A transient traumatic spinal cord modeling system, characterized in that, Includes a robotic arm (1), a gripper (2), an optical motion capture module, and a control module; The clamp (2) is installed on the drive end of the robotic arm (1). At least one clamping surface of the clamp (2) is provided with an array of pressure sensors (3), and at the tip of at least one clamping surface of the clamp (2) is provided with a fiber optic grating force sensor (4). The robotic arm (1) can drive the clamp (2) to move and open and close. The robotic arm (1) is equipped with a piezoelectric-electromagnetic composite actuator (5), and the driving end of the piezoelectric-electromagnetic composite actuator (5) is connected to the driving end of the clamp (2). The optical motion capture module is installed on the experimental platform to monitor and calibrate the position and posture of the clamp (2) on the robotic arm (1) relative to the mouse spinal cord; The control module is connected to the robotic arm (1), the piezoelectric-electromagnetic composite actuator (5), the array pressure sensor (3), the fiber optic force sensor (4), and the optical motion capture module.

2. The transient traumatic spinal cord modeling system according to claim 1, characterized in that, It also includes a high-speed camera (6) installed on the experimental platform, which is used to record the process of the clamp (2) clamping the mouse spinal cord, and the high-speed camera (6) is connected to the control module.

3. The instantaneous traumatic spinal cord modeling system according to claim 2, characterized in that, It also includes a displacement sensor installed on the drive end of the robotic arm (1), the displacement sensor can measure the opening displacement of the clamp (2), and the displacement sensor is connected to the control module.

4. A method for transient traumatic spinal cord modeling, characterized in that, The system for creating a transient traumatic spinal cord model as described in claim 3 includes the following steps: Step 1: Prepare the mice surgically according to the experimental objectives and plan the movement paths of the robotic arm (1) and clamp (2); Step 2: The control module drives the robotic arm (1) to move the clamp (2) along the motion route planned in Step 1 to the target spinal cord segment of the animal and keep the clamp (2) in an open mouth posture. The position and posture of the robotic arm (1) and the clamp (2) are calibrated and confirmed by the optical motion capture module. Step 3: The control module issues an instantaneous control command to drive the jaws of the clamp (2) to close and clamp the target spinal cord segment of the animal by the piezoelectric-electromagnetic composite actuator (5). At the same time, the operation of the piezoelectric-electromagnetic composite actuator (5) is adjusted according to the data stream from the piezoelectric-battery composite actuator, fiber optic force sensor (4), high-speed camera (6), and displacement sensor until the millisecond-level precise clamping injury of the spinal cord is completed. Step 4: Verify the consistency of spinal cord injury in mice.

5. The method for transient traumatic spinal cord modeling according to claim 4, characterized in that, In step three, the data stream includes real-time jaw pressure distribution data from the piezoelectric-electromagnetic composite actuator (5), instantaneous jaw clamping force data from the fiber optic force sensor (4), jaw contact time data with the spinal cord from the high-speed camera (6), and jaw opening and closing displacement data from the displacement sensor.

6. The method for transient traumatic spinal cord modeling according to claim 5, characterized in that, Contact time data between the jaws and the spinal cord from the high-speed camera (6) were obtained through the following steps: After the high-speed camera (6) acquires an image set of the process of clamping the spinal cord with the jaws, the contact time between the jaws and the spinal cord is calculated based on the number of the images of the jaws contacting the spinal cord and the number of the images of the jaws separating from the spinal cord in the image set, as well as the frame rate of the high-speed camera (6).

7. A method for transient traumatic spinal cord modeling according to claim 6, characterized in that, In step three, the operation of the piezoelectric-electromagnetic composite actuator (5) is adjusted according to the following steps: S31: Obtain the data stream; S32: Process the data stream to obtain the jaw pressure distribution data, jaw instantaneous clamping force data, jaw opening and closing displacement data, and jaw contact time with the spinal cord when the jaws of the clamp (2) are closed, and determine whether the data meets the experimental target. If it meets the experimental target, proceed to S33; if it does not meet the experimental target, proceed to S34. S33: Control the clamp (2) and the robotic arm (1) to work according to the preset experimental route; S34: Execute S31 to process the data stream and determine whether the clamp (2) is in contact with the spinal cord. If it is in contact, execute S35; if it is not in contact, execute S36. S35: Perform step one and replace the mouse; S36: Perform step one and replan the motion path of the robotic arm (1) and the clamp (2).

8. A method for transient traumatic spinal cord modeling according to claim 4, characterized in that, In step four, the consistency of spinal cord injury in mice is verified through one or more of the following steps: S41: Real-time biomechanical verification: Process the data in the data stream and determine whether the data is within the error range of the spinal cord injury modeling experimental design. If so, the injury is consistent; otherwise, the injury is inconsistent. S42: Postoperative functional assessment: Long-term behavioral tracking of mice that meet the modeling goals to assess the damage and recovery of their neurological function. S43: Quantitative histopathological analysis: Spinal cord tissue from mice with spinal cord injury model was prepared into sections, stained, and analyzed to assess collagen deposition and nerve damage in the spinal cord injury area.

9. A method for transient traumatic spinal cord modeling according to claim 4, characterized in that, After step three is completed, the mouse is hemostatically stopped and sutured. A heating pad is used to maintain the mouse's body temperature until it wakes up. Depending on the mouse's condition, physiological saline is administered subcutaneously and analgesics are given to relieve pain.

10. A method for transient traumatic spinal cord modeling according to claim 4, characterized in that, After step four is completed, the mechanical data and displacement data of the clamp (2) are recorded and the mechanical data and displacement data are processed to verify the stability of the repeated modeling experiment.

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