In-vitro bone force-electrical property measuring device based on complex impedance and piezoelectric property measurement

Abstract

The invention discloses an in-vitro bone force-electrical property measuring device based on complex impedance and piezoelectric property measurement. The in-vitro bone force-electrical property measuring device comprises a workbench, an in-vitro bone clamping module, an axial pressure output module, a complex impedance measuring module and a main control module. The in-vitro bone clamping module is used for clamping an in-vitro bone; the axial pressure output module is used for applying axial pressure to the in-vitro bone clamped by the in-vitro bone clamping module, and a pressure sensor used for measuring the actual stress value of the in-vitro bone is arranged in the axial pressure output module; the complex impedance measurement module is used for collecting complex impedance data between any two points on the surface of the in-vitro bone under different axial pressures; the main control module is used for controlling the axial pressure output module to work and regulating and controlling the output pressure of the axial pressure output module according to the actual stress value fed back by the pressure sensor and the initial set value; and the main control module is also used for receiving the complex impedance data and calculating the piezoelectric voltage of the in-vitro bone according to the complex impedance data.

Description

Technical Field

[0001] The present invention belongs to the field of bone voltage measurement, and in particular relates to an in vitro bone force-electric property measurement device based on complex impedance and piezoelectric property measurement. Background Art

[0002] The mechanical-electrical properties of bone, namely stress-generated potentials (SGP), reflect the potential changes generated by bone when subjected to mechanical forces. As researchers delve into the biomechanical properties of bone, SGP is considered to be one of the important factors affecting bone reconstruction and adaptability. Specifically, when ex vivo bone is subjected to different mechanical forces, non-uniform piezoelectric voltage will be generated inside the bone due to the non-uniform distribution of charge. This piezoelectric voltage is not only related to the physical state of the bone, but may also play a key role in the physiological function and repair process of bone tissue. However, there are some challenges in measuring piezoelectric voltage. The charges generated by the piezoelectric effect are difficult to maintain because they can easily disappear through the discharge of the material itself. Therefore, the piezoelectric voltage of ex vivo bone can usually only be manifested under dynamic load, which requires the testing equipment to be able to adapt to a variety of loading conditions.

[0003] As researchers delve deeper into the study of bone piezoelectric voltage, direct piezoelectric response acquisition of different parts of ex vivo bone (such as the bone surface, bone layer, and bone marrow) has become an emerging research direction. In order to obtain accurate piezoelectric response signals, a suitable axial pressure method must be adopted. Published studies have shown that the use of trapezoidal pulses can effectively stimulate ex vivo bone and obtain the corresponding piezoelectric voltage waveform. By analyzing waveform characteristics and constructing fitting functions, researchers can perform theoretical simulations of experimental results, thereby gaining a deeper understanding of the mechanical-electrical properties of ex vivo bone under different mechanical conditions.

[0004] Currently, the following test modules are used to study the mechanical-electrical properties of bones: 1. An improved electro-hydraulic servo fatigue testing machine, which directly measures the piezoelectric voltage of bones by loading ex vivo bone slices and combining it with an acquisition module. The operator records and processes the data to analyze the mechanical-electrical properties of bones; 2. A micro-biomechanical testing machine, which mainly studies the mechanical properties of bones by performing tensile and compression experiments on ex vivo bones; 3. A bone potential measurement system, which collects the patient's in vivo bone potential in real time, improving the efficiency of medical staff in analyzing bone healing.

[0005] However, the current experimental devices used to study the mechanical-electrical properties of bone have the following defects during use:

[0006] First, existing solutions all directly measure piezoelectric voltage, which only reflects the magnitude of the force applied and does not contain internal information such as bone density and tissue status. Bone piezoelectric voltage is typically a weak signal with high impedance and is easily affected by EMI and environmental noise, making direct measurement difficult to ensure its accuracy.

[0007] Secondly, the micro biomechanical testing machine is limited to studying the mechanical properties of isolated bones and lacks the function of collecting biopotentials, making it impossible to synchronously collect the piezoelectric voltage under axial pressure.

[0008] In addition, due to the limitations of single-physics field monitoring (e.g., electrical signals or mechanical parameters only), existing bone potential measurement systems are unable to simultaneously apply and dynamically control axial mechanical pressure, resulting in the lack of multi-physics field coupling model construction, which in turn hinders researchers' in-depth exploration of the mechanical-electrical properties of bone.

[0009] Finally, the existing modules for detecting the mechanical and electrical properties of bones are only suitable for sliced ​​ex vivo bones. Slicing will destroy the integrity of the ex vivo bones, making it difficult to reflect the true structure and mechanical properties of the ex vivo bones in the living state. This limits the universality and clinical application value of the research results. Summary of the Invention

[0010] In order to overcome the shortcomings of the existing technology, the present invention provides an in vitro bone force-electric property measurement device based on complex impedance and piezoelectric property measurement. The in vitro bone force-electric property measurement device can measure the piezoelectric voltage of the in vitro bone under different axial pressures with higher measurement accuracy.

[0011] The technical solution of the present invention to solve the above technical problems is:

[0012] A device for measuring the mechanical and electrical properties of an ex vivo bone based on complex impedance and piezoelectric characteristic measurements, comprising a workbench, an ex vivo bone clamping module disposed on the workbench, an axial pressure output module, a complex impedance measurement module, and a main control module, wherein the ex vivo bone clamping module is used to clamp the ex vivo bone; the axial pressure output module is used to apply axial pressure to the ex vivo bone clamped by the ex vivo bone clamping module, the axial pressure output module being provided with a pressure sensor for measuring the actual force value of the ex vivo bone, the pressure sensor transmitting the actual force value to the main control module; the complex impedance measurement module is used to collect complex impedance data between any two points on the surface of the ex vivo bone under different axial pressures, and transmit the measured complex impedance data to the main control module; the main control module is used to control the operation of the axial pressure output module, and to regulate the output pressure of the axial pressure output module using a built-in PID algorithm model based on the actual force value fed back by the pressure sensor and an initial set value; the main control module is also used to receive the complex impedance data measured by the complex impedance measurement module and calculate the piezoelectric voltage of the ex vivo bone based on the complex impedance data.

[0013] Preferably, the ex vivo bone clamping module includes a clamping platform, a first clamp arranged on the clamping platform, a second clamp and a spacing adjustment mechanism for adjusting the horizontal spacing between the first clamp and the second clamp, wherein the clamping platform is installed on the workbench; the two ends of the ex vivo bone to be measured are clamped in the first clamp and the second clamp respectively.

[0014] Preferably, the axial force output module includes a fixing seat, a servo electric cylinder arranged on the fixing seat, and a transmission mechanism for transmitting the output force of the servo electric cylinder to the ex vivo bone, wherein the transmission mechanism includes an optical axis; one end of the optical axis is connected to the first clamp or the second clamp through a double-headed screw, and the second clamp or the first clamp is connected to the spacing adjustment mechanism; the other end of the optical axis is installed on the output shaft of the servo electric cylinder through a threaded connection structure.

[0015] Preferably, a linear guide mechanism is provided between the optical axis and the first clamp or the second clamp for guiding the linear motion of the optical axis; the linear guide mechanism includes a guide seat provided on the workbench and a linear bearing provided on the guide seat and the clamping platform and cooperating with the optical axis.

[0016] Preferably, the pressure sensor is arranged in the servo electric cylinder to monitor the actual force value applied to the ex vivo bone in real time, and convert it into an electrical signal and transmit it to the main control module.

[0017] Preferably, the complex impedance measurement module includes a flexible array electrode, a multiplexer module and an electrical impedance detection module, wherein the flexible array electrode is installed on the ex vivo bone, and the flexible array electrode includes an electrode carrier and a plurality of equally spaced metal circular electrode disks arranged in the electrode carrier; the electrode carrier adopts a flexible substrate; the back side of each metal circular electrode disk is electrically connected to the multiplexer module through a flexible wire; the multiplexer module is connected to the main control module; the electrical impedance detection module is connected to the multiplexer module, and is used to measure the complex impedance between any two points on the surface of the ex vivo bone.

[0018] Preferably, a human-computer interaction module is also included, which is used for researchers to set axial pressure parameters and to achieve synchronous real-time display, data storage and correlation analysis of mechanical parameters and electrical signals.

[0019] Preferably, the main control module includes an ADC unit, a PID regulator, a serial communication unit, a calculation unit and an SPI communication unit, wherein the serial communication unit is used to receive the axial pressure parameters transmitted by the human-computer interaction module and output them to the PID regulator; the ADC unit is used to convert the pressure signal monitored by the pressure sensor into a digital signal and output it to the PID regulator; the PID regulator is used to combine the axial pressure parameters input by the human-computer interaction module and the actual force value fed back by the pressure sensor, and generate a driving signal through a built-in PID algorithm model, and transmit it to the axial pressure output module; the SPI communication unit is used to receive the complex impedance value fed back by the electrical impedance detection module and transmit it to the calculation unit; the calculation unit calculates the piezoelectric voltage of the ex vivo bone based on the complex impedance data, combined with the equivalent circuit model and the piezoelectric model.

[0020] Preferably, the piezoelectric voltage of the isolated bone is calculated as follows:

[0021] Load the corresponding bone tissue equivalent circuit topology library based on anatomical partitioning;

[0022] An RC series equivalent circuit model was used, in which the internal environment of the bone cell was equivalent to a resistor and the double-layer cell membrane structure was equivalent to a capacitor. The complex impedance data corresponding to the measurement path were iteratively fitted using a nonlinear least squares algorithm to extract the equivalent resistance and capacitance values.

[0023] Calculating a first product of the equivalent capacitance value and the center-to-center distance between two metal circular electrode disks in the measurement path, and a second product of the area of ​​the metal circular electrode disk in the flexible array electrode and the vacuum dielectric constant, and calculating a first ratio of the first product and the second product to obtain the relative dielectric constant between any two metal circular electrode disks;

[0024] The piezoelectric constant of the isolated bone, the third product of the distance between the two metal circular electrode disks in the measurement path and the axial pressure, and the fourth product of the relative dielectric constant between any two metal circular electrode disks and the vacuum dielectric constant are calculated. The piezoelectric potential of the isolated bone is obtained by calculating the second ratio of the third product and the fourth product.

[0025] Preferably, the nonlinear least squares algorithm adopts the Levenberg-Marquardt nonlinear least squares algorithm.

[0026] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0027] 1. The in vitro bone force-electric property measurement device based on complex impedance and piezoelectric property measurement of the present invention can output programmable axial pressure to act on the research object (ex vivo bone), and at the same time accurately collect the complex impedance between any two points on the surface of the in vitro bone (for example, most in vitro bones such as tibia, femur, vertebrae, and skull) at different parts under different axial pressures. The piezoelectric voltage between the above two points is calculated by combining the equivalent circuit model and the piezoelectric model, and the relevant data is displayed and saved, thereby achieving the purpose of studying the force-electric properties of the in vitro bone under different axial pressures, allowing researchers to deeply explore the force-electric properties of the bone and provide reliable data support for the research and clinical application of the endogenous electric field of the bone.

[0028] 2. The present invention's in vitro bone mechano-electrical property measurement device, based on complex impedance and piezoelectric properties measurements, significantly enhances the ability to study bone mechano-electrical properties and enables multifunctional applications at a lower cost. Compared to traditional fatigue servo testing machines, the present invention's in vitro bone mechano-electrical property measurement device offers low cost, compact size, simple operation, low energy consumption, and high safety.

[0029] 3. The axial pressure output module in the in vitro bone force-electric property measurement device based on complex impedance and piezoelectric characteristic measurement of the present invention has sensitive dynamic response, supports precise control of small force values ​​or complex axial pressure, and the flexible in vitro bone clamping module can firmly and stably clamp in vitro bones at different parts. The flexibility of the in vitro bone clamping module is suitable for clamping a variety of complex in vitro bones to facilitate axial pressure output, thereby avoiding the limitations brought by a single loading method; therefore, the in vitro bone force-electric property measurement device of the present invention solves the problem of lack of precise control of axial pressure in existing bone potential measurement systems, and promotes the correlation research of the force-electric properties of bones.

[0030] 4. Compared with the traditional direct measurement method of piezoelectric signals, which is susceptible to electromagnetic interference, weak signals and difficult to collect stably, the in vitro bone mechanical-electrical property measurement device of the present invention indirectly infers the piezoelectric voltage through electrical impedance spectroscopy (EIS), and has higher stability and adaptability. Among them, the electrical impedance measurement adopts an excitation-response mechanism, which still has a good signal-to-noise ratio when facing high-impedance (MΩ level) biological tissues such as in vitro bones, and can effectively suppress the influence of environmental noise. At the same time, the EIS measurement not only reflects the voltage amplitude, but also provides the complex impedance characteristics of the material under multi-frequency response, which can reveal the microstructural information of bone tissue, such as bone density, cracks, porosity, etc., and provide rich structural basis for the accurate estimation of the piezoelectric model, thereby ensuring the scientific nature of the research on the mechanical-electrical properties of bones. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1This is a structural block diagram of the in vitro bone mechanical-electrical property measurement model based on complex impedance and piezoelectric property measurement of the present invention.

[0032] Figure 2 and Figure 3 Schematic diagrams of the three-dimensional structure of the in vitro bone mechanical-electrical property measurement model based on complex impedance and piezoelectric property measurement from two different perspectives of the present invention.

[0033] Figure 4 This is a front view of the in vitro bone mechanical-electrical property measurement model based on complex impedance and piezoelectric property measurement of the present invention.

[0034] Figure 5 This is a top view of the in vitro bone mechanical-electrical property measurement model based on complex impedance and piezoelectric property measurement of the present invention.

[0035] Figure 6 A three-dimensional diagram of a flexible array electrode.

[0036] Figure 7 This is the equivalent circuit model diagram.

[0037] Figure 8 This is the measurement result in Example 2.

[0038] In the figure: 1-workbench; 2-servo electric cylinder; 3-optical axis; 4-clamping platform; 5-guide seat; 6-main control module and complex impedance measurement module; 7-first clamp; 8-adjustment screw; 9-flexible array electrode; 901-electrode carrier; 902-metal circular electrode disk; 10-second clamp; 11-flexible wire. DETAILED DESCRIPTION

[0039] The present invention will be described in further detail below with reference to the embodiments and drawings, but the embodiments of the present invention are not limited thereto.

[0040] Example 1

[0041] See also Figures 1-7 The in vitro bone mechanical-electrical property measurement device based on complex impedance and piezoelectric characteristic measurement of the present invention includes a workbench 1, an in vitro bone clamping module arranged on the workbench 1, an axial pressure output module, a complex impedance measurement module and a main control module, wherein:

[0042] The workbench 1 serves as the foundation for the axial pressure output module, providing a stable experimental platform and supporting flexible adjustment of the positions of the ex vivo bone clamping module and the axial pressure output module. It offers both flexibility and stability. The workbench is equipped with M6 threaded holes spaced 25mm apart, allowing researchers to adjust the positions of the modules based on the size of the ex vivo bone. The entire workbench 1 is constructed of T6-6061 aluminum alloy and weighs 4kg. The bottom feet of the workbench 1 are equipped with anti-slip material to protect against external interference during the axial pressure output process.

[0043] The ex vivo bone clamping module is used to clamp the ex vivo bone;

[0044] The axial pressure output module is used to apply axial pressure to the ex vivo bone clamped by the ex vivo bone clamping module. The axial pressure output module is provided with a pressure sensor for measuring the actual force value of the ex vivo bone. The pressure sensor transmits the actual force value to the main control module;

[0045] The complex impedance measurement module is used to collect complex impedance data between any two points on the ex vivo bone surface under different axial pressures, and transmit the measured complex impedance data to the main control module;

[0046] The main control module is used to control the operation of the axial pressure output module, and according to the actual force value and the initial set value fed back by the pressure sensor, uses the built-in PID algorithm (or fuzzy control, adaptive control, neural network control) to regulate the output pressure of the axial pressure output module; the main control module is also used to receive the complex impedance data measured by the complex impedance measurement module, and use it to calculate the piezoelectric voltage of the ex vivo bone.

[0047] During operation, researchers can set the amplitude, cycle and output times of the axial pressure and the configuration of the multiplexer module through the human-machine interface (HMI) to meet different experimental needs; the in vitro bone clamping module can firmly clamp the research object (ex vivo bone), while the axial pressure output module can ensure the uniqueness of the force transmission direction and detect the force condition of the ex vivo bone in real time; by combining the negative feedback mechanism, precise control of the axial pressure amplitude is achieved, ensuring the stability of the axial pressure output; the complex impedance measurement module can accurately measure the complex impedance between any two points on the surface of different parts of the ex vivo bone; the main control module calculates the piezoelectric voltage between the above two points based on the equivalent circuit model and the piezoelectric model, and finally the main control module transmits the relevant data to the human-machine interface for display and saves the relevant data.

[0048] See also Figures 1-7 The ex vivo bone clamping module includes a clamping platform 4, a first clamp 7 arranged on the clamping platform 4, a second clamp 10, and a spacing adjustment mechanism for adjusting the horizontal spacing between the first clamp 7 and the second clamp 10, wherein the clamping platform 4 is installed on the workbench 1; the two ends of the ex vivo bone to be measured are clamped in the first clamp 7 and the second clamp 10 respectively.

[0049] In this embodiment, the ex vivo bone clamping module is used to firmly clamp ex vivo bones of different shapes, with both stability and flexibility; the clamping platform 4 adopts a mechanical structure with a length of 166 mm, a width of 80 mm and a height of 50 mm; the first clamp 7 and the second clamp 10 are both cylinders with a radius of 4 mm and a height of 4 mm, with an M3 thread with a depth of 2 mm at the bottom and a spherical groove with a radius of 1 mm at the top to adapt to the shape of the ex vivo bone; the spacing adjustment mechanism is an adjusting screw 8, the thread length of the adjusting screw 8 is 50 mm and the diameter is 3 mm, and the adjusting screw 8 passes through the threaded hole on the clamping platform 4 and is connected to the first clamp 7 through a threaded connection structure, which is used to adjust the spacing / relative position of the first clamp 7 and the second clamp 10, so as to fix different types of ex vivo bones and complete the clamping of the ex vivo bones; the second clamp 10 is connected to the optical axis 3 by a double-headed screw; the first clamp 7 and the second clamp 10 are used to clamp the two ends of the ex vivo bone.

[0050] In addition, the supporting models of the adjusting screw 8, the first clamp 7 and the second clamp 10 can be replaced to adapt to different sizes of ex vivo bones. That is, researchers can choose the models of the first clamp 7 and the second clamp 10 that are suitable according to the size and shape of the ex vivo bones. By turning the adjusting screw 8, the horizontal axial positions of the first clamp 7 and the second clamp 10 can be fine-tuned to achieve firm clamping of ex vivo bones of different lengths.

[0051] See also Figures 1-7 To accommodate the diverse shapes of ex vivo bones at different locations and ensure simple and precise control of axial pressure, the present device is designed with the following axial pressure output module. The axial force output module includes a fixed seat disposed on a workbench 1, a servo electric cylinder 2 (or pneumatic cylinder, hydraulic cylinder) disposed on the fixed seat, and a transmission mechanism for transmitting the output force of the servo electric cylinder 2 to the ex vivo bone. The transmission mechanism includes an optical axis 3. One end of the optical axis 3 is connected to the second clamp 10 by a stud screw, and the other end is mounted on the output shaft of the servo electric cylinder 2 by a threaded connection structure.

[0052] In this embodiment, the transmission mechanism is used to transmit the output force of the servo electric cylinder 2 to the ex vivo bone. The transmission mechanism is composed of an optical axis 3 with a length of 90 mm, a diameter of 5 mm and an M3 thread on the inner wall; in order to improve the movement accuracy of the optical axis 3, a linear guide mechanism is also provided between the optical axis 3 and the second clamp 10, and the linear guide mechanism includes a guide seat 5 arranged on the workbench 1 and a linear ball bearing matched with the optical axis 3 arranged on the guide seat 5 and the clamping platform 4, wherein there are two linear ball bearings, and the length of the two linear ball bearings is 8 mm, the outer diameter is 10 mm and the inner diameter is 5 mm; by equipping a circular flange with a diameter of 15 mm, the diameter of the mounting hole of the circular flange is 3 mm, so that the two linear ball bearings are respectively fixed to the clamping platform 4 and the guide seat 5 by M3 hexagon socket screws; the centers of the two linear ball bearings and the center of the cross section of the optical axis 3 are located on the same axis, and the optical axis 3 passes through the two linear ball bearings to form a stable transmission mechanism.

[0053] When the servo electric cylinder 2 outputs axial pressure, the optical axis 3 transmits the axial pressure to the second clamp 10 and the ex vivo bone; wherein, the two linear ball bearings can ensure that the axial pressure output by the servo electric cylinder 2 is stably transmitted along the axial direction, while decomposing the eccentric force, thereby avoiding deviations in the experimental data caused by the eccentric force; the transmission mechanism can achieve high efficiency and low loss in axial pressure transmission, thereby ensuring the uniqueness of the axial pressure direction, thereby reducing errors caused by eccentric force; in addition, the low friction characteristics of the transmission mechanism can reduce vibration and component wear during the force application process, thereby enhancing the reliability of the experiment and the service life of the device.

[0054] In this embodiment, the servo electric cylinder 2 is a linear actuator that integrates a servo motor and a screw transmission mechanism. It performs precise linear motion according to the drive signal sent by the main control module. The servo electric cylinder 2 has a motion stroke of 16 mm, an axial pressure accuracy of 0.1 N, and a maximum force value of 105 N. It has a built-in drive module for processing and executing the drive signal sent by the main control module to drive the screw transmission mechanism to achieve axial pressure output; in addition, the servo electric cylinder 2 combines a negative feedback mechanism to achieve rapid response to ensure high efficiency and robustness of the axial pressure output, thereby avoiding errors caused by manual adjustment and improving the accuracy and efficiency of the experiment.

[0055] See also Figures 1-7The pressure sensor is arranged in the servo electric cylinder 2, and is used to monitor the actual force value applied to the ex vivo bone in real time, and convert it into an electrical signal and transmit it to the main control module; in this embodiment, the pressure sensor is built into the servo electric cylinder 2, and has a measurement accuracy of 0.1N and a measurement range of -100N to 100N. Combined with a high response speed, it accurately captures the force changes of the ex vivo bone. The pressure sensor continuously collects force value data and feeds it back to the main control module in real time, thereby supporting the detection and adjustment of the axial pressure output.

[0056] See also Figures 1-7 The complex impedance measurement module includes a flexible array electrode 9, a multiplexer module and an electrical impedance detection module, wherein:

[0057] The flexible electrode array 9 is mounted on the ex vivo bone and includes an electrode carrier 901 and a plurality of equally spaced metal circular electrode disks 902 (i.e., electrodes) disposed within the electrode carrier 901. The electrode carrier 901 is made of a flexible substrate. The back surface of each metal circular electrode disk 902 is electrically connected to the multiplexer module via a flexible wire 11.

[0058] In order to adapt to the diversity of ex vivo bone shapes at different locations, this embodiment uses a flexible array electrode 9 suitable for placement on the surface of the ex vivo bone. The flexible array electrode 9 is made of a flexible, conformable material and has multiple channels (eight are used as an example in this embodiment and can be selected according to experimental needs). The flexible array electrode 9 is fixed to the surface of the ex vivo bone according to experimental requirements to construct multiple measurement paths.

[0059] In addition, the flexible array electrode 9 is as follows Figure 6 As shown, its overall size is 10mm×18mm and its thickness is about 1mm; the flexible array electrode 9 is composed of a plurality of equally spaced circular collection units, each collection unit being a metal circular electrode disk 902 with a diameter of 2mm, made of a metal material with stable conductive properties (such as silver-plated copper or metal composite film); the center spacing between each metal circular electrode disk 902 is 6mm; the minimum distance between the edge of the flexible array electrode 9 and the array frame is 1mm to ensure that the boundary effect is minimized and a mechanical buffer zone is left; the back of each metal circular electrode disk 902 is led out through a flexible wire 11 and electrically connected to an external multiplexer module for realizing dynamic switching of the conductive path between the metal circular electrode disks 902; in addition, the electrode carrier 901 is made of a flexible substrate (such as polyimide or PDMS), so that it has good adhesion and conformability, and can stably adhere to irregular surfaces such as bone tissue to realize multi-point collection of local electrical signals.

[0060] In addition, the flexible array electrode 9 is connected to the electrical impedance detection module through the multiplexer module, and the main control module activates the measurement channel between any two electrodes according to the set program to obtain their complex impedance spectrum data.

[0061] The multiplexer module is used to select and switch any measurement channel in the flexible array electrode 9, and constitutes the core electrode path control unit of the system. The multiplexer module is internally integrated with multiple programmable analog switch arrays, which supports flexible switching of connection relationships between multiple input / output channels; in this embodiment, the multiplexer module is connected to the flexible array electrode 9, and each metal circular electrode disk 902 is connected to the input port of the switch array through an independent wire; the main control module can program and configure the multiplexer module through SPI, thereby activating the conduction path of any two electrode channels; the use of this dynamic switching mechanism enables the system to measure the complex impedance data between any two points on the surface of the ex vivo bone, thereby greatly improving the spatial coverage and testing flexibility of the system.

[0062] The electrical impedance detection module is used to measure the complex impedance between any two points on the surface of ex vivo bone, realizing multi-frequency, high-resolution complex impedance measurement; the impedance of ex vivo bone is as high as the MΩ level, and the piezoelectric voltage signal is often weak and susceptible to electromagnetic interference. Complex impedance measurement is an excitation-response system with a higher signal-to-noise ratio, which can accurately measure the complex impedance so as to calculate the accurate piezoelectric voltage.

[0063] The electrical impedance detection module operates based on the principle of AC impedance spectroscopy analysis and employs an integrated impedance conversion chip (or a professional LCR impedance analyzer) internally. This integrated impedance conversion chip applies a set of sinusoidal excitation signals of preset frequencies to the bone tissue to be tested via a built-in frequency generator and synchronously measures the resulting current signal. The integrated impedance conversion chip has a built-in digital-to-analog converter (DAC) to output the excitation source, samples the response voltage via an analog-to-digital converter (ADC), and then uses a digital Fourier transform (DFT) algorithm to extract the real and imaginary parts of the signal at each frequency point to calculate the complex impedance value of the tissue at that frequency, thereby achieving impedance measurement with an accuracy of ±1% from 1 Hz to 1 MHz. This measurement method has the advantages of simple structure, high precision, and a wide measurement range, and is suitable for analyzing the electrical properties of biological tissues such as ex vivo bone.

[0064] See also Figures 1-7 The in vitro bone mechanical-electrical property measurement device based on complex impedance and piezoelectric characteristic measurement of the present invention also includes a human-computer interaction module, which is used for researchers to set axial pressure parameters and to achieve synchronous real-time display, data storage and correlation analysis of mechanical parameters and electrical signals;

[0065] In this embodiment, the human-computer interaction module (human-computer interaction interface) is the data analysis center of the device, which is responsible for setting the axial pressure parameters and receiving the data transmitted by the main control module in real time, realizing the synchronous real-time display, data storage and correlation analysis of mechanical parameters (pressure, frequency) and electrical signals (complex impedance, piezoelectric voltage); researchers conduct data analysis through the human-computer interaction interface, and then conduct in-depth research on the mechanical-electrical properties of bones; axial pressure parameters (including amplitude, period and output times), multiplexer configuration and complex impedance measurement parameters are sent through the human-computer interaction interface, and the main control module drives the axial pressure output module to generate a closed-loop loading sequence based on the preset parameters; real-time mechanical data fed back by the pressure sensor and piezoelectric voltage data calculated by the calculation unit are synchronously received, and after transmission via the SPI / serial port dual bus, the time domain waveform is synchronously visualized and structured stored on the human-computer interaction interface;

[0066] In addition, the main control module and the human-computer interaction module can use wireless communication (such as Bluetooth, WiFi) in addition to serial communication.

[0067] See also Figures 1-7 The main control module is the control center of the device, which is responsible for sending a driving signal to the axial pressure output module to generate accurate and stable axial pressure, receiving and processing the data output by the complex impedance measurement module in real time, and calculating the piezoelectric voltage and transmitting it to the human-computer interaction interface. The main control module includes an ADC unit, a PID regulator, a serial communication unit, a calculation unit and an SPI communication unit. The main control module uses a microprocessor as the core, has high performance and low power consumption, and is suitable for real-time signal processing and control tasks. Among them, the serial communication unit is used to receive the axial pressure parameters transmitted by the human-computer interaction module and output it to PID regulator; the ADC unit is used to convert the pressure signal monitored by the pressure sensor into a digital signal and output it to the PID regulator; the PID regulator is used to combine the axial pressure parameter input by the human-computer interaction module and the actual force value fed back by the pressure sensor, generate a driving signal through the built-in PID algorithm model, and transmit it to the axial pressure output module; the SPI communication unit is used to receive the complex impedance value fed back by the electrical impedance detection module and transmit it to the calculation unit; the calculation unit calculates the piezoelectric voltage of the ex vivo bone based on the complex impedance data, combined with the equivalent circuit model and the piezoelectric model;

[0068] In this embodiment, the ADC unit has high precision and fast response capabilities, and is suitable for collecting the output of the pressure sensor in the axial pressure output module; the PID regulator automatically adjusts the PID parameters according to the set value, generates a calibrated drive signal and transmits it to the servo cylinder 2 of the axial pressure output module, thereby achieving precise axial pressure control; the serial communication unit supports USART serial communication, transmits data with the human-computer interaction module, receives axial pressure parameters (i.e., set values), and supports system debugging and troubleshooting; the calculation unit is used to perform core computing tasks such as equivalent circuit model fitting and piezoelectric voltage estimation; the SPI communication unit performs high-speed data transmission with the electrical impedance detection module through the SPI communication protocol, supports parallel communication, and improves the data transmission efficiency of the overall system.

[0069] See also Figures 1-7 The working principle of the in vitro bone mechanical-electrical property measurement device based on complex impedance and piezoelectric property measurement of the present invention is:

[0070] On the workbench 1, researchers adjusted the positions of the bone clamping module, the transmission mechanism, and the servo electric cylinder 2 according to the size of the bone, and used the bone clamping module to firmly clamp the bone.

[0071] Subsequently, the amplitude, cycle and output times of the axial pressure are set in the human-computer interaction interface; in the main control module, the serial communication unit communicates with the human-computer interaction module, receives the target value of the axial pressure and transmits it to the PID regulator; the ADC unit receives the actual force value fed back by the pressure sensor in the axial pressure output module; the PID regulator outputs a driving signal according to the target value and the actual force value; the SPI communication unit receives the complex impedance data measured by the electrical impedance detection module; the calculation unit calculates the piezoelectric voltage based on the complex impedance data, combined with the equivalent circuit model and the piezoelectric model; the axial pressure output The servo electric cylinder 2 in the module outputs axial pressure after receiving the driving signal of the main control module, and ensures the unique transmission direction of the force through the transmission mechanism; the pressure sensor detects the actual force value of the isolated bone in real time and transmits it to the main control module. The axial pressure output module combines the negative feedback mechanism to achieve precise control of the axial pressure amplitude to ensure the stability and controllability of the axial pressure output; the multiplexer module communicates with the main control module and dynamically switches the measurement channel according to the settings of the host computer; the electrical impedance detection module is connected to the bone surface through the flexible array electrode 9 (adjustable spacing, electrode density ≥16 points / cm 2) applies a broadband AC excitation of 0.1 Hz-10 MHz, and a multiplexer module (switching time <100 ns) dynamically selects the measurement channel to obtain the complex impedance spectrum data (including resistance term (R), reactance term (X) and phase angle θ) between any two points on the bone surface, and transmits it back to the main control module via the SPI bus (transmission rate ≥10 Mbps); the built-in computing unit of the main control module loads the corresponding bone tissue equivalent circuit topology library (Cole-Cole model) based on the in vitro bone anatomical partition identifier (cortical bone / cancellous bone), and obtains the equivalent capacitance value C and the equivalent resistance value R through Levenberg-Marquardt algorithm fitting, and then inserts them into the piezoelectric equation to derive the piezoelectric voltage.

[0072] Ultimately, the human-computer interaction module realizes the synchronous real-time display, data storage and correlation analysis of mechanical parameters (pressure, frequency) and electrical signals (complex impedance, piezoelectric voltage); each module works together through a standardized communication protocol to accurately establish the mapping relationship between axial pressure excitation and piezoelectric voltage response, providing a high-precision experimental platform for in-depth research on the mechanical-electrical properties of bone tissue.

[0073] During the complex impedance measurement process, the SPI communication unit of the main control module uses the SPI communication protocol to perform high-speed data transmission with the complex impedance module, receiving complex impedance data in real time. From a bioelectrochemical perspective, the response of ex vivo bone tissue to an alternating electric field can be characterized by the frequency-varying characteristics of impedance (Z), which can be mathematically decomposed into a complex combination of resistance (R) and reactance (X):

[0074] Z(ω)=R(ω)+jX(ω);

[0075] In the process of fitting the equivalent circuit model of ex vivo bone tissue, the corresponding bone tissue equivalent circuit topology library (Cole-Cole model) is first loaded based on the anatomical partitioning (cortical bone / cancellous bone). The classic RC series equivalent circuit model is used, in which the internal environment of the bone cell is equivalent to the resistor R and the double-layer cell membrane structure is equivalent to the capacitor C. The impedance parameters corresponding to the measurement path are iteratively fitted using the Levenberg-Marquardt nonlinear least squares algorithm, and the equivalent resistance value R and capacitance value C are finally extracted. The frequency domain total impedance formula of this equivalent circuit model is described, and the parameters are optimized to achieve the best match between the simulation curve and the measured impedance spectrum data, thereby obtaining the key parameters reflecting the electrophysiological characteristics of bone tissue. The frequency domain total impedance is given by the following formula:

[0076]

[0077] Combined with the frequency conversion formula ω=2πf, the equivalent capacitance expression is derived as follows:

[0078]

[0079] Furthermore, the calculation unit substitutes the capacitance value C obtained by fitting and the known electrode structure parameters (including the electrode area A and the electrode spacing d) into the capacitance formula:

[0080]

[0081] To calculate the relative dielectric constant between any two points e r , among which ε0 is the dielectric constant of vacuum;

[0082] In the process of piezoelectric voltage calculation, based on the piezoelectric coupling equation and the open-circuit condition, the typical expression of the voltage generated by any two points of the isolated bone along the polarization direction under the action of force can be derived as follows:

[0083]

[0084] Its physical meaning is: when a normal stress F is applied to a piezoelectric material with a thickness of d, a voltage V will be generated in that direction. piezo , and is related to the piezoelectric constant and dielectric properties of the material; where d is the actual thickness distance between the electrodes, which is equivalent to the electrode spacing in the aforementioned capacitance calculation; the stress value F is detected by the pressure sensor, and the piezoelectric constant of the isolated bone d 33 Set by the human-computer interface;

[0085] Through the above-mentioned calculation process, the calculation unit can output the piezoelectric voltage caused by stress between any two points in the isolated bone; the serial communication unit of the main control module communicates with the human-computer interaction interface through the serial port, transmits, displays and stores piezoelectric voltage data and force values ​​in real time, and supports real-time data analysis.

[0086] In addition, the in vitro bone mechanical-electrical property measurement of the present invention is also applicable to in vivo bone detection of living animals, and only the in vitro bone clamping module needs to be replaced.

[0087] In summary, the in vitro bone force-electric property measurement device based on complex impedance and piezoelectric property measurement of the present invention can output a programmable axial pressure, act on the research object (ex vivo bone), and simultaneously accurately measure the complex impedance between any two points on the surface of the in vitro bone (most in vitro bones such as tibia, femur, vertebrae, and skull) at different locations under different axial pressures. The piezoelectric voltage is calculated by combining the equivalent circuit model and the piezoelectric model, and the relevant data is displayed and stored. Therefore, the in vitro bone force-electric property measurement device of the present invention has the following advantages:

[0088] (1) Synchronous acquisition, display and analysis of force-electricity curves:

[0089] The calculated piezoelectric voltage is displayed synchronously with the system's axial pressure curve. The force value curve and multi-point piezoelectric voltage curve are simultaneously plotted through the human-computer interaction interface, intuitively showing the relationship between the intrabone potential response and axial pressure, facilitating analysis and research by researchers and providing an efficient analysis tool.

[0090] (2) Axial pressure output is stable and controllable:

[0091] Equipped with an axial pressure output module with force feedback, it allows researchers to precisely control the axial pressure amplitude, cycle, and output times, and supports a variety of complex axial pressure output methods, including periodic axial compression.

[0092] (3) The flexible array electrode 9 is constructed so that the device can adapt to irregular bone surfaces and support complex impedance measurement between any electrode pairs;

[0093] (4) Impedance spectrum measurement and equivalent circuit fitting: The resistance and capacitance parameters in the equivalent RC series circuit model are fitted based on the complex impedance measured by the complex impedance measurement module;

[0094] (5) Piezoelectric model mapping: piezoelectric voltage is calculated based on the fitted capacitance value and piezoelectric model;

[0095] (6) Mathematical mapping model from equivalent circuit to dielectric constant to piezoelectric voltage: used to convert the parameters measured by complex impedance into piezoelectric voltage, suitable for accurate measurement and analysis of weak piezoelectric signals with high impedance;

[0096] (7) The present invention innovatively proposes an in situ piezoelectric response detection method based on fresh ex vivo bone tissue samples. By using fresh ex vivo bone samples from multiple anatomical parts including tibia, femur, vertebrae and skull, piezoelectric signal detection is performed while maintaining the physiological water content and intact microstructure of the tissue. Compared with the traditional bone slice drying detection method, the present invention can effectively avoid the destruction of the bone matrix collagen-hydroxyapatite microstructure caused by sample dehydration treatment, and the interference of stress release on the intrinsic piezoelectric properties of bone tissue during slice preparation, and for the first time achieves the precise capture of the characteristic signal of the piezoelectric effect of bone tissue.

[0097] Example 2

[0098] The in vitro bone force-electric property measurement device based on complex impedance and piezoelectric property measurement of the present invention is used to estimate the piezoelectric voltage between points 1 and 3 of the tibia of a 12-week-old mouse under cyclic compression conditions and draw a force-electric curve and an electrical impedance spectrum analysis curve. The axial pressure output module outputs axial compression with a period of 3 seconds, an amplitude of 8N, and 5 cycles. The specific implementation steps are as follows:

[0099] Step 1: Connect and start the device;

[0100] Connect the servo cylinder 2 and the main control module with a cable and turn on their respective power supplies. Then start the human-machine interface, servo cylinder 2, and main control module. In the human-machine interface, select the serial port corresponding to the main control module and open it to enable communication between the human-machine interface and the main control module.

[0101] Step 2: Installation of various mechanisms and modules;

[0102] Adjust the positions of the clamping platform 4, servo electric cylinder 2, and wire clamping platform 4 on the workbench 1 according to the size of the tibia, and fix them to the workbench 1 with M6 hexagon socket screws;

[0103] Step 3: Preparation of ex vivo bone (taking fresh ex vivo tibia as an example);

[0104] This experiment used freshly excised tibia specimens from 12-week-old mice. Rapid euthanasia was achieved using isoflurane anesthesia (5% induction concentration) combined with cervical dislocation. Anatomical-grade time-sensitive procedures were performed in a cleanroom: the hind limb bones were severed within 2 minutes of death and immediately transferred to a 4°C cryogenic operating platform. Minimally invasive muscle dissection was performed using microsurgery instruments (less than 8 minutes), preserving the periosteal structure and three-dimensional configuration of the bone units.

[0105] Step 4: Installing the isolated bone and the flexible array electrode 9;

[0106] Select the appropriate fixture, optical axis 3, and flexible array electrode 9 according to the size of the tibia, and turn the adjustment screw clockwise so that the tibia can be stably mounted between the first fixture 7 and the second fixture 10; install the treated tibia in the clamping platform 4, clamp the two ends of the tibia with the first fixture 7 and the second fixture 10 respectively, and use the flexible array electrode 9 to stably contact the tibia to be measured;

[0107] Step 5: Select the measurement point;

[0108] Select channels 1 and 3 through the human-computer interaction interface and configure the multiplexer module to activate channels 1 and 3;

[0109] Step 6: Tibia electromechanical characteristics experiment;

[0110] Enter an axial pressure amplitude of 8N, a period of 3 seconds, and 5 axial pressure output times on the human-computer interaction interface. Click the measurement function on the human-computer interaction interface, and the axial pressure output module will begin to apply axial pressure to the tibia. At the same time, the complex impedance measurement module will measure the electrical impedance data between points 1 and 3 on the tibia surface when squeezed by the axial pressure output module in real time. After the main control module calculates the piezoelectric voltage, the force-electricity characteristic curve is drawn on the human-computer interaction interface.

[0111] Step 7: Replace the ex vivo bone;

[0112] Turn the adjusting screw counterclockwise to remove the tibia. After removing the test probe from the tibia, the tibia is removed and stored in a test tube. The isolated bone can then be replaced and the experiment can be repeated, and then batch experiments can be carried out.

[0113] like Figure 8 As shown in the figure, the experimental results are: the human-computer interaction interface displays the tibial force curve, the electrical impedance spectrum analysis curve between points 1 and 3 on the tibia (taking the complex impedance of static measurement as an example) and the piezoelectric voltage curve in real time. The above curves are drawn synchronously, and researchers can analyze the mechanical and electrical characteristics of the bone based on the curves.

[0114] The above is a preferred embodiment of the present invention, but the embodiment of the present invention is not limited to the above content. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the scope of protection of the present invention.

Claims

1. An in vitro bone mechanical-electrical property measurement device based on complex impedance and piezoelectric property measurement, characterized in that: The invention comprises a workbench, an ex vivo bone clamping module arranged on the workbench, an axial pressure output module, a complex impedance measurement module and a main control module, wherein the ex vivo bone clamping module is used to clamp the ex vivo bone; the axial pressure output module is used to apply axial pressure to the ex vivo bone clamped by the ex vivo bone clamping module, and the axial pressure output module is provided with a pressure sensor for measuring the actual force value of the ex vivo bone, and the pressure sensor transmits the actual force value to the main control module; the complex impedance measurement module is used to collect complex impedance data between any two points on the surface of the ex vivo bone under different axial pressures, and transmit the measured complex impedance data to the main control module; the main control module is used to control the operation of the axial pressure output module, and adopts a built-in PID algorithm model to regulate the output pressure of the axial pressure output module according to the actual force value fed back by the pressure sensor and the initial set value; the main control module is also used to receive the complex impedance data measured by the complex impedance measurement module, and calculate the piezoelectric voltage of the ex vivo bone based on it.

2. The in vitro bone mechanical-electrical property measurement device based on complex impedance and piezoelectric characteristic measurement according to claim 1, characterized in that: The ex vivo bone clamping module includes a clamping platform, a first clamp arranged on the clamping platform, a second clamp, and a spacing adjustment mechanism for adjusting the horizontal spacing between the first clamp and the second clamp, wherein the clamping platform is installed on the workbench; the two ends of the ex vivo bone to be measured are clamped in the first clamp and the second clamp respectively.

3. The in vitro bone mechanical-electrical property measurement device based on complex impedance and piezoelectric property measurement according to claim 2, characterized in that: The axial force output module includes a fixing seat, a servo electric cylinder arranged on the fixing seat, and a transmission mechanism for transmitting the output force of the servo electric cylinder to the ex vivo bone, wherein the transmission mechanism includes an optical axis; one end of the optical axis is connected to the first clamp or the second clamp through a double-headed screw, and the second clamp or the first clamp is connected to the spacing adjustment mechanism; the other end of the optical axis is installed on the output shaft of the servo electric cylinder through a threaded connection structure.

4. The in vitro bone mechanical-electrical property measurement device based on complex impedance and piezoelectric property measurement according to claim 3, characterized in that: A linear guide mechanism is also provided between the optical axis and the first fixture or the second fixture for guiding the linear motion of the optical axis; the linear guide mechanism includes a guide seat provided on the workbench and a linear bearing provided on the guide seat and the clamping platform and cooperating with the optical axis.

5. The in vitro bone mechanical-electrical property measurement device based on complex impedance and piezoelectric property measurement according to claim 3, characterized in that: The pressure sensor is arranged in the servo electric cylinder and is used to monitor the actual force value applied to the isolated bone in real time, and convert it into an electrical signal to transmit to the main control module.

6. The in vitro bone mechanical-electrical property measurement device based on complex impedance and piezoelectric property measurement according to claim 5, characterized in that: The complex impedance measurement module includes a flexible array electrode, a multiplexer module and an electrical impedance detection module, wherein the flexible array electrode is installed on the ex vivo bone, and the flexible array electrode includes an electrode carrier and a plurality of equally spaced metal circular electrode disks arranged in the electrode carrier; the electrode carrier adopts a flexible substrate; the back of each metal circular electrode disk is electrically connected to the multiplexer module through a flexible wire; the multiplexer module is connected to the main control module; the electrical impedance detection module is connected to the multiplexer module, and is used to measure the complex impedance between any two points on the surface of the ex vivo bone.

7. The in vitro bone mechanical-electrical property measurement device based on complex impedance and piezoelectric characteristic measurement according to claim 6, characterized in that: It also includes a human-computer interaction module, which is used for researchers to set axial pressure parameters and to achieve synchronous real-time display, data storage and correlation analysis of mechanical parameters and electrical signals.

8. The in vitro bone mechanical-electrical property measurement device based on complex impedance and piezoelectric property measurement according to claim 7, characterized in that: The main control module includes an ADC unit, a PID regulator, a serial communication unit, a calculation unit and an SPI communication unit, wherein the serial communication unit is used to receive the axial pressure parameters transmitted by the human-computer interaction module and output them to the PID regulator; the ADC unit is used to convert the pressure signal monitored by the pressure sensor into a digital signal and output it to the PID regulator; the PID regulator is used to combine the axial pressure parameters input by the human-computer interaction module and the actual force value fed back by the pressure sensor, and generate a driving signal through a built-in PID algorithm model, and transmit it to the axial pressure output module; the SPI communication unit is used to receive the complex impedance value fed back by the electrical impedance detection module and transmit it to the calculation unit; the calculation unit calculates the piezoelectric voltage of the ex vivo bone based on the complex impedance data, combined with the equivalent circuit model and the piezoelectric model.

9. The in vitro bone mechanical-electrical property measurement device based on complex impedance and piezoelectric property measurement according to claim 8, characterized in that: The calculation process of the piezoelectric voltage of the isolated bone is: Load the corresponding bone tissue equivalent circuit topology library based on anatomical partitioning; An RC series equivalent circuit model was used, in which the internal environment of the bone cell was equivalent to a resistor and the double-layer cell membrane structure was equivalent to a capacitor. The complex impedance data corresponding to the measurement path were iteratively fitted using a nonlinear least squares algorithm to extract the equivalent resistance and capacitance values. Calculating a first product of the equivalent capacitance value and the center-to-center distance between two metal circular electrode disks in the measurement path, and a second product of the area of ​​the metal circular electrode disk in the flexible array electrode and the vacuum dielectric constant, and calculating a first ratio of the first product and the second product to obtain the relative dielectric constant between any two metal circular electrode disks; The piezoelectric constant of the isolated bone, the third product of the distance between the two metal circular electrode disks in the measurement path and the axial pressure, and the fourth product of the relative dielectric constant between any two metal circular electrode disks and the vacuum dielectric constant are calculated. The piezoelectric potential of the isolated bone is obtained by calculating the second ratio of the third product and the fourth product.

10. The in vitro bone mechanical-electrical property measurement device based on complex impedance and piezoelectric property measurement according to claim 9, characterized in that: The nonlinear least squares algorithm adopts the Levenberg-Marquardt nonlinear least squares algorithm.

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