Piezoelectric driving device for dynamic testing of mechanical characteristics of cells

Abstract

The invention relates to a piezoelectric driving device for dynamic testing of mechanical characteristics of cells, and belongs to the technical field of precise motion driving. The device comprises a driving foot, a clamping foot, a fixed guide rail, a movable guide rail, a pre-tightening force adjusting unit, a base, a T-shaped bracket, an extension bar, a biological pressure head, a cell container, a force sensor and a displacement sensor. The driving foot and the clamping foot are composed of piezoelectric stacks, triangular amplification driving heads and square blocks. The device has two working modes, wherein the first mode is stepping motion and is used for large-stroke positioning to the preloading depth; and the mode II is cyclic dynamic loading and is used for dynamically exciting the cells. The mechanical response and displacement data of the cells are obtained in real time through the force sensor and the displacement sensor, so that the mechanical characteristics such as the energy storage modulus and the loss modulus are calculated. The device is simple in structure, integrates two working modes, can realize broadband dynamic testing, and is suitable for the fields of biomedicine and precision engineering.

Description

Technical Field

[0001] This invention relates to the field of piezoelectric precision drive technology, and in particular to a piezoelectric drive device for dynamic testing of cellular mechanical properties. Background Technology

[0002] With the deepening of life science and medical research, the mechanical properties of cells have become a key indicator for assessing their physiological state and diagnosing related diseases (such as cancer and arteriosclerosis). Traditional methods for detecting cellular mechanical properties, such as static indentation and micropipette adsorption using atomic force microscopy (AFM), mostly rely on static or quasi-static loading methods. These methods can usually only obtain a single parameter of the cell in equilibrium (such as static elastic modulus), but cannot reflect the viscoelastic response of the cell under dynamic loading. This dynamic property is crucial for understanding the true physiological behavior of cells because: First, cells exist in a dynamic physiological environment. Within the living body, cells are constantly subjected to dynamic mechanical stimuli. For example, vascular endothelial cells experience the periodic shear forces of blood flow; cardiomyocytes contract and relax rhythmically with the heartbeat; and chondrocytes endure reciprocating compressive loads during joint movement. Therefore, the mechanical properties of cells are inherently frequency-dependent, and their response to external loads includes both elastic (energy storage) and viscous (dissipation) components, i.e., viscoelasticity. Static testing alone cannot capture this frequency-dependent mechanical behavior.

[0003] Secondly, viscoelasticity is directly related to cell structure and function. Cellular viscoelasticity primarily stems from the dynamic reorganization of the internal cytoskeleton (such as actin and microtubules) and the flow characteristics of the cytoplasm. Storage modulus (G') reflects the solid elastic characteristics and structural stability of the cytoskeleton, while loss modulus (G'') reflects the degree of energy dissipation within the cell, closely related to the flow and reorganization of intracellular substances. Dynamic viscoelastic parameters (such as the loss factor tanδ = G'' / G') can reveal the pathological state of cells more sensitively and comprehensively than static elastic modulus. For example, numerous studies have shown that cancer cells typically exhibit lower storage modulus and higher loss factor compared to normal cells—that is, they are "softer and stickier"—a characteristic key to their highly invasive behavior.

[0004] Furthermore, static testing has limitations. Existing detection devices that combine electromechanical characteristics (such as those disclosed in CN117210320B), although functionally integrated, still fall into the quasi-static category in their mechanical testing components. They cannot provide wide-bandwidth, controllable dynamic excitation, making it difficult to accurately measure the dynamic modulus of cells or to study the mechanical relaxation and creep behavior of cells under simulated physiological dynamic environments.

[0005] In summary, designing a piezoelectric drive device that can provide wide-bandwidth, controllable dynamic excitation to achieve precise measurement of cell dynamic viscoelasticity has become the key to breaking through existing technological bottlenecks and promoting biomedical research from static characterization to dynamic biomimetic testing. Summary of the Invention

[0006] The purpose of this invention is to overcome the shortcomings of existing technologies and provide a wideband, controllable dynamic excitation piezoelectric drive device. This device, through a dual-operating-mode design, integrates the functions of achieving large-stroke stepping motion and performing micro-nano-level dynamic excitation. Based on a high-frequency response piezoelectric stack and a high-rigidity mechanical structure, it provides the core capability for generating wideband, precise dynamic excitation, specifically for high-precision testing of the dynamic mechanical properties of cells.

[0007] To achieve the above objectives, the present invention adopts the following technical solution: a piezoelectric driving device for dynamic testing of cell mechanical properties, comprising: a base, a movable guide rail slidably mounted on the base, a driving unit, a clamping unit, and a measuring unit; the driving unit includes a driving foot, and the clamping unit includes at least one clamping foot arranged along the movable guide rail; both the driving foot and the clamping foot contain at least one piezoelectric driving element and act on the movable guide rail; The device is configured to have two operating modes: Working mode 1: Stepping motion mode, which uses alternating excitation clamping to clamp / release the moving guide rail and excitation drive to generate stepping displacement, thus realizing the large stroke stepping motion of the moving guide rail; Working mode 2: Cyclic load dynamic loading mode, which applies a dynamic excitation signal to the drive foot to make the moving guide rail reciprocate micro-motion; the measurement unit includes a displacement sensor for detecting the displacement of the moving guide rail and a force sensor for detecting the loading force; In this mode, the pressure head connected to the moving guide rail is driven to the preload position through working mode one, and then the working mode two is switched to dynamically load the sample. The dynamic mechanical properties of the sample are calculated based on the real-time data from the displacement sensor and the force sensor.

[0008] Furthermore, the clamping unit includes clamping feet one and clamping feet two arranged at intervals along the moving guide rail.

[0009] Furthermore, the driving foot is positioned between the clamping foot one and the clamping foot two.

[0010] Furthermore, both the drive foot and the clamping foot include a triangular amplification drive head for outputting driving force.

[0011] Furthermore, the piezoelectric drive device also includes a preload adjustment unit for adjusting the force between the drive foot and the clamping foot and the moving guide rail.

[0012] Furthermore, the preload adjustment unit includes a micrometer screw.

[0013] Furthermore, in operating mode one, the rise time of the excitation signal for the foot is greater than the rise time of the excitation signal for the clamping foot.

[0014] Furthermore, in operating mode two, the dynamic excitation signal applied to the driving foot is a sine wave signal.

[0015] Furthermore, dynamic mechanical properties include energy storage modulus, loss modulus, and loss factor.

[0016] The core of this invention lies in providing a piezoelectric driving device, which integrates large-stroke coarse positioning and micro / nano-level dynamic precision excitation functions through the coordinated arrangement of a driving foot and at least one clamping foot, configured to perform two working modes: stepping motion and dynamic cyclic load loading. Both the driving foot and the clamping foot contain piezoelectric driving elements and act on the same moving guide rail. By controlling the timing and waveform of the excitation signal, the two modes are switched and coordinated. Based on this, combined with displacement and force sensors, high-precision measurement of the dynamic viscoelastic properties of cells is achieved. Specifically: (1) Dynamic testing capability: Through a high-stiffness, low-inertia direct drive structure, high-fidelity broadband dynamic excitation is achieved in working mode 2 to fully characterize the viscoelastic properties of cells and overcome the limitations of traditional static testing. (2) Structural integration innovation: The alternating excitation mechanism of driving foot and clamping foot is adopted to replace the complex flexible hinge mechanism, which makes the structure simpler and the control more precise; (3) Dual-mode collaboration: Integrating step positioning and dynamic loading, it achieves seamless switching from macro positioning to micro excitation, ensuring the in-situ nature of the test and the accuracy of the benchmark; (4) Real-time monitoring and analysis: Data is acquired in real time through sensors and dynamic parameters are calculated to improve testing efficiency and accuracy. Attached Figure Description

[0017] Figure 1 This is a schematic diagram of the overall structure of the present invention; Figure 2 This is a schematic diagram of the driver of the present invention; Figure 3 This is a diagram of the driving signals for the first working mode of the present invention; Figure 4 This is a diagram of the driving signals for the second working mode of the present invention; Figure 5 A diagram of the experimental apparatus of the present invention; Figure 6 Force-displacement diagram; Figure 7Plots showing the changes in storage modulus and loss modulus of mouse mammary tumor cells with frequency. Figure 8 This is a comparison image of mouse mammary tumor cells and normal mammary cells. Detailed Implementation

[0018] The present invention will now be further described with reference to the accompanying drawings.

[0019] like Figure 1 and Figure 2 As shown, the present invention includes a driving foot 2, a clamping foot one 1, a clamping foot two 3, a fixed guide rail 14, a moving guide rail 13, a preload adjustment unit 4, a base 6, a T-shaped bracket 7, a fixing screw one 5, a fixing screw two 12, an extension rod 11, a bio-pressure head 10, a cell container 9, a force sensor 8, a support 15, and a displacement sensor 16. The base 6 is fixed to the T-shaped bracket 7 with screws. The driving foot 2, clamping foot one 1, and clamping foot two 3 are fixed in the sliding holes of the base 6 with fixing screw one 5. The fixed guide rail 14 is fixed to the base 6 with fixing screw two 12 and slides relative to the moving guide rail 13 via bearings. The six micrometer screws of the preload adjustment unit 4 are used to adjust the preload. The extension rod 11 connects the moving guide rail 13 and the bio-pressure head 10. The cell container 9 and the force sensor 8 are located below the bio-pressure head 10. The displacement sensor 16 is fixed to the support 15 and points towards the moving guide rail 13. Clamping foot 1 consists of piezoelectric stack 1-1, piezoelectric stack 2-2, delta amplifier drive head 1-5, and square block 1-3, and is connected by two long screws 1-4. Clamping foot 2 consists of piezoelectric stack 3-1, piezoelectric stack 2-2, delta amplifier drive head 3-5, and square block 3-3, and is connected by two long screws 3-4. Driving foot 2 consists of piezoelectric stack 2-1, piezoelectric stack 2-2, delta amplifier drive head 2-5, and square block 2-3, and is connected by two long screws 2-4.

[0020] like Figure 5 As shown, the experimental system of the present invention is connected in the following manner: the output terminal of the signal generator is connected to the piezoelectric drive device via a power amplifier to provide it with an excitation signal; the output terminals of the force sensor 8 and the displacement sensor 16 are respectively connected to the digital-to-analog converter and the controller to convert the analog signal into a digital signal and transmit it to the host computer for processing, wherein the digital-to-analog converter is powered by a DC power supply.

[0021] The work process is as follows: First, the bio-pressure head 10 is moved downwards to the preload depth using operating mode one (stepping motion). For example... Figure 3As shown, initially, clamping foot 1 and clamping foot 2 are activated to lock the moving guide rail 13. Then, clamping foot 1 and clamping foot 2 are released and driving foot 2 is activated to slowly extend, pushing the moving guide rail 13 downward. This process is repeated until the preload depth is reached, which is monitored by displacement sensor 16.

[0022] Then, switch to working mode two (dynamic loading), as follows: Figure 4 As shown, the clamping foot is stopped, and only the driving foot 2 is given a sinusoidal signal to dynamically load the cell with the bio-pressure head 10. Simultaneously, the force sensor 8 detects the cell's mechanical response, and the displacement sensor 16 detects the displacement. The data is uploaded to the host computer, and a force-displacement diagram is plotted (e.g., ...). Figure 6 ), and calculate the mechanical properties of the cells.

[0023] The host computer processes the collected force and displacement data, specifically including the following steps: 1. The voltage signals collected by the force sensor and displacement sensor are converted into time series data of stress σ(t) and strain ε(t) respectively through calibration coefficients.

[0024] 2. Draw a force-displacement diagram, perform spectral analysis on the stress and strain signals, and extract the stress amplitude σ0, strain amplitude ε0, and phase difference δ between them at the excitation frequency.

[0025] 3. Based on linear viscoelasticity theory, the dynamic mechanical properties of cells are calculated using the following formula: The formula for calculating the storage modulus is as follows: The formula for calculating the loss modulus is: The formula for calculating the loss factor is: .

[0026] like Figure 7 As shown, the storage modulus significantly increases with increasing excitation frequency, while the loss modulus remains relatively stable. This phenomenon clearly reveals the solid-like mechanical behavior dominated by the cytoskeleton network within the tested cells: under high-frequency rapid deformation, the molecular network exhibits a "lock-in" effect due to insufficient time for recombination, resulting in enhanced elastic response; the stable loss modulus indicates that its viscous dissipation mechanism was not activated within the test frequency band. This typical viscoelastic spectral characteristic not only verifies the effectiveness of the dynamic detection method of this invention, but also provides a crucial dynamic mechanical fingerprint for distinguishing cell states (such as the stable structure of normal cells and the softening characteristics of cancer cells).

[0027] like Figure 8As shown, the loss factor of mouse mammary tumor cells (0.12) was lower than that of normal mammary cells (0.17). This data indicates that tumor cells exhibit more significant "solid-like" elastic characteristics in their physical nature, with a weakened internal viscous dissipation mechanism. This change in mechanical properties is closely related to the enhanced invasiveness of tumor cells, thus verifying that the method described in this invention can identify the pathological state of cells and providing a novel, quantitative biophysical marker for the mechanical diagnosis of cancer.

[0028] This invention has a simple structure, integrates two working modes, and realizes dynamic testing of cell mechanical properties, which has broad application prospects.

[0029] The above description is merely a preferred embodiment of the present invention, and the scope of protection of the present invention is not limited thereto. Any modifications, equivalent substitutions, and improvements made within the principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A piezoelectric drive device for dynamic testing of cellular mechanical properties, characterized in that, include: The base (6), a movable guide rail (13) slidably mounted on the base (6), a drive unit, a clamping unit, and a measuring unit; the drive unit includes a drive foot (2), and the clamping unit includes at least one clamping foot arranged along the movable guide rail (13); both the drive foot (2) and the clamping foot contain at least one piezoelectric drive element and act on the movable guide rail (13). The device is configured to have two operating modes: Working mode 1: Stepping motion mode, by alternately stimulating the clamp to clamp / release the moving guide rail (13) and stimulating the driving foot (2) to generate stepping displacement, the large stroke stepping motion of the moving guide rail (13) is realized; Working mode 2: Cyclic load dynamic loading mode, by applying a dynamic excitation signal to the driving foot (2), the moving guide rail (13) is made to reciprocate micro-motion; the measuring unit includes a displacement sensor (16) for detecting the displacement of the moving guide rail (13) and a force sensor (8) for detecting the loading force. In this process, after the pressure head (10) connected to the moving guide rail (13) is driven to the preload position by working mode one, the working mode two is switched to dynamically load the sample, and the dynamic mechanical properties of the sample are calculated based on the real-time data of the displacement sensor (16) and the force sensor (8).

2. The piezoelectric drive device for dynamic testing of cell mechanical properties according to claim 1, characterized in that, The clamping unit includes clamping feet one (1) and clamping feet two (3) arranged at intervals along the moving guide rail (13).

3. The piezoelectric drive device for dynamic testing of cell mechanical properties according to claim 2, characterized in that, The driving foot (2) is positioned between the clamping foot one (1) and the clamping foot two (3).

4. The piezoelectric drive device for dynamic testing of cell mechanical properties according to claim 1, characterized in that, Both the driving foot (2) and the clamping foot include a triangular amplifying driving head (1-5) for outputting driving force.

5. The piezoelectric drive device for dynamic testing of cell mechanical properties according to claim 1, characterized in that, It also includes a preload adjustment unit (4) for adjusting the force between the drive foot (2) and the clamping foot and the moving guide rail (13).

6. The piezoelectric drive device for dynamic testing of cell mechanical properties according to claim 5, characterized in that, The preload adjustment unit (4) includes a micrometer screw.

7. The piezoelectric drive device for dynamic testing of cell mechanical properties according to claim 1, characterized in that, In the first working mode, the rise time of the signal that excites the driving foot (2) is greater than the rise time of the signal that excites the clamping foot.

8. The piezoelectric drive device for dynamic testing of cell mechanical properties according to claim 1, characterized in that, In the second working mode, the dynamic excitation signal applied to the driving foot (2) is a sine wave signal.

9. The piezoelectric drive device for dynamic testing of cell mechanical properties according to claim 1, characterized in that, The dynamic mechanical properties include energy storage modulus, loss modulus, and loss factor.

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