Design method and device of force-position switching controller of piezoelectric driven cell microinjector and injection method thereof

Abstract

The application discloses a design method and device of a force-position switching controller of a piezoelectric-driven cell microinjector and an injection method thereof, and comprises the following steps: S1: based on the deformation and viscoelasticity of cells, a mass-spring-damper system is used to establish a dynamic model for describing a system formed by the microinjector and the cells; S2: based on the dynamic model, an adaptive integral terminal sliding mode impedance force controller is designed; S3: based on a feedforward compensator and a feedback control law, a composite PID position controller is designed; S4: a switching function is designed; and S5: the switching control law of the final force-position switching controller is calculated by combining the adaptive integral terminal sliding mode impedance force controller, the PID position controller and the switching function. The force-position switching controller can provide accurate force and position tracking performance in each control mode, and still has small chattering and cell damage degree when different modes are switched multiple times.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of biological cell microinjection, and particularly relates to a design method and device of a force-position switching controller of a piezoelectric-driven cell microinjector and an injection method thereof. BACKGROUND

[0002] Microinjection technology has become a key means in biological research and medical applications, which helps to accurately deliver exogenous substances into cells and is widely used in intracytoplasmic sperm injection, drug research and development, and gene editing. It is crucial for a microinjection system to achieve high precision and reliability, especially when dealing with biological cells with complex characteristics. Piezoelectric-driven microinjectors can significantly improve system control and rapid response capabilities. However, due to the deformation, fragility, and complex viscoelastic mechanical properties of biological cells (such as stress relaxation), it is difficult to predict the relationship between the puncture force and cell deformation, resulting in the inability to control mechanical damage. In addition, the inherent nonlinear hysteresis effect (with rate-dependent and non-symmetric characteristics) of the piezoelectric driver also poses a major challenge to the accurate position output of the microinjector. In addition, dynamic switching between force control and position control modes needs to be performed multiple times during the entire cell injection process, which can easily trigger force overshoot and chattering phenomena, which may lead to unstable control systems. SUMMARY

[0003] The first object of the present application is to provide a design method of a force-position switching controller of a cell microinjector that can achieve stable and smooth transition during switching.

[0004] The second object of the present application is to provide a force-position switching device of a piezoelectric-driven cell microinjector.

[0005] The third object of the present application is to provide an injection method of a force-position switching device of a piezoelectric-driven cell microinjector.

[0006] Technical solution: The design method of a force-position switching controller of a piezoelectric-driven cell microinjector disclosed by the present application comprises the following steps,

[0007] S1: Based on the deformation and viscoelasticity of cells, a mass-spring-damper system is used to establish a dynamic model for describing the system formed by the microinjector and the cells;

[0008] S2: Based on the dynamic model, an adaptive integral terminal sliding mode impedance force controller is designed to suppress the influence of the viscoelastic mechanical characteristics of the cells;

[0009] S3: A compound PID position controller is designed to suppress the piezoelectric hysteresis nonlinearity by selecting a feedforward compensator and a feedback control law;

[0010] S4: Design a switching function for switching the adaptive integral terminal sliding mode impedance force controller and the composite PID position controller based on the double Sigmoid function switching criterion;

[0011] S5: Obtain the switching control law of the final force-position switching controller by combining the adaptive integral terminal sliding mode impedance force controller, the PID position controller and the switching function.

[0012] Further, the expression of the dynamic model in step S1 is as follows:

[0013] ,

[0014] where m represents the mass of the cell microinjector, c represents the damping of the cell microinjector, k represents the stiffness of the cell microinjector, x represents the measured output displacement of the cell microinjector, represents the output velocity of the cell microinjector, represents the output acceleration of the cell microinjector, b represents the voltage coefficient, u represents the input voltage of the piezoelectric driving device, represents the measured contact force between the cell microinjector and the cell membrane, represents the lumped disturbance term.

[0015] Further, the steps of designing the adaptive integral terminal sliding mode impedance force controller for suppressing the influence of the cell viscoelastic mechanical characteristics in step S2 are as follows:

[0016] S21: Use the nonlinear Hunt-Crossley model to establish the H-C model for describing the cell viscoelastic mechanical characteristics, and the H-C model is used to characterize the contact force between the cell microinjector and the cell membrane ;

[0017] S22: When the cell microinjector contacts the cell and the cell membrane no longer deforms, it is called that the cell reaches a steady state, and the position of the cell when it reaches the steady state is set as the equilibrium position , and the cell is in the equilibrium position , the force output by the adaptive integral terminal sliding mode impedance force controller is set as the desired force , and the Taylor formula is used to expand the H-C model at , to obtain the expansion formula of the H-C model for describing the contact force and the desired force ;

[0018] S23: When the cell microinjector contacts the cell, the force applied to the cell microinjector by the cell membrane is resistance, and when the cell reaches a steady state, the adaptive integral terminal sliding mode resistance force controller adjusts the contact force by adjusting the desired resistance between the cell microinjector and the cell, and sets the desired resistance equation based on the generalized resistance control idea;

[0019] S24: Based on the expansion formula of the H-C model and the desired resistance equation, the desired viscoelastic resistance kinetic model when the cell reaches a steady state is calculated, the corresponding steady state force error equation when the cell reaches a steady state is calculated based on the viscoelastic resistance kinetic model, the convergence condition when the steady state force error converges to zero is calculated based on the steady state force error equation, and the desired resistance equation in step S23 is updated based on the convergence condition to obtain an updated desired resistance equation;

[0020] S25: The auxiliary variable g of the terminal sliding mode for establishing the adaptive integral terminal sliding mode resistance force controller is designed in combination with the updated desired resistance equation;

[0021] S26: The integral type terminal sliding mode surface of the adaptive integral terminal sliding mode resistance force controller is designed based on the auxiliary variable g in step S25;

[0022] S27: Based on the integral type terminal sliding mode surface in step S26, the state variable is selected; and where s refers to the sliding mode surface of the integral type terminal sliding mode, refers to the first derivative of s;

[0023] S28: The expected value of the state variable is defined as , and where , , are constant parameters, is a time-varying parameter, and , , ; and the error z between the state variable and its expected value ;

[0024] S29: Based on the kinetic model, the auxiliary variable g, and the state variable , the final adaptive integral terminal sliding mode resistance force controller is obtained.

[0025] Further, the expression of the H-C model in step S21 is: where represents the stiffness coefficient of the cell, represents the damping coefficient of the cell, and n represents a constant greater than zero;

[0026] The expression of the H-C model in step S22 is: wherein , ;

[0027] The expression of the desired impedance equation in step S23 is: wherein denotes the desired position; denotes the position tracking error, ; denotes the force tracking error, ; , , , denotes the target parameter of the generalized impedance;

[0028] The expression of the viscoelastic impedance dynamics model in step S24 is as follows:

[0029] ;

[0030] When the cell is in a steady state, , , , that is, wherein is a steady-state position error; the steady-state force error is calculated in combination with the desired impedance equation and the steady-state position error , and the expression of the steady-state force error is , and the convergence condition is determined based on the expression , and the updated desired impedance equation is ;

[0031] The expression of the auxiliary variable g in step S25 is wherein denotes the force tracking error filtered by a first-order filter, and the expression of the first-order filter is wherein is the first-order derivative of , , ;

[0032] The expression of the sliding surface of the integral terminal sliding mode in step S26 is: wherein k1, k2 and are constant parameters, and , , , ;

[0033] The expression for the error z in step S28 is: ;

[0034] The expression for the adaptive integral terminal sliding mode impedance controller in step S29 is as follows: ,in , , For robustness, It is the upper bound of the unknown disturbance. The estimated value, and , where parameters .

[0035] Furthermore, the feedforward compensator in step S3 is a feedforward compensator based on the fractional-order Bouc-Wen model, and the expression for this feedforward compensator is: ,in As an auxiliary lagged variable, and , where parameters , , , , , , Used to determine the shape of the hysteresis loop, and , , , This represents the Caputo fractional derivative.

[0036] Furthermore, the feedback control law in step S3 employs PID control. ,in For proportional control gain, For integral control gain, This is the differential control gain.

[0037] Furthermore, the switching function in step S4 is: ,in , , This indicates the current moment; the cell microinjector begins its uniform delivery from a preset position until it contacts the cell. The uniform movement of the cell microinjector towards the cell is position-controlled, and the moment of contact between the cell microinjector and the cell is [the current moment]. ; The timing at which the cell microinjector begins to switch from position control to force control is preset with a time interval for this switch. This indicates the initial moment when the control has switched from position control to force control; This indicates the moment when the cell membrane is penetrated by the cell microinjector. The cell microinjector is switched from force control to position control at time t0, and the time interval for switching from force control to position control is set in advance, represents the initial time at which the switching from force control to position control is performed; and parameter is used to adjust the shape of the switching function, and the numerical value is proportional to the switching rate.

[0038] Further, the switching control law of the force-position switching controller in step S5 is .

[0039] Based on the same inventive concept, the application further discloses a piezoelectric-driven cell microinjector, comprising a piezoelectric driver, a force-position switching controller for controlling and electrically connected to the output end of the piezoelectric driver, a connecting rod connected to the output end of the electric driver through a connecting member, a micro-force sensor connected to the other end of the connecting rod through another connecting member and used for measuring the contact force, and a micro-injection needle installed at the end of the micro-force sensor, and the micro-force sensor is electrically connected to an external displacement sensor for measuring the output displacement thereof.

[0040] Based on the same inventive concept, the application further discloses an injection method of a piezoelectric-driven cell microinjector force-position switching device, comprising the following steps,

[0041] switching the force-position switching controller to position control and driving the micro-injection needle to move to a preset position;

[0042] The micro-injection needle moves at a constant speed to the target cell under the position control mode of the force-position switching controller, the micro-force sensor detects the contact force between the micro-injection needle and the target cell membrane in real time, when the contact force exceeds a preset threshold, the force-position switching controller is switched from position control to force control, and the switching time interval is set in advance; wherein the time at which the contact force exceeds the preset threshold is time t1, based on the switching time interval and time t0, the time t2 is calculated, at which time the force-position switching controller is switched to force control;

[0043] The micro-injection needle contacts the target cell membrane under the force control mode of the force-position switching controller, the micro-force sensor detects the contact force between the micro-injection needle and the target cell membrane in real time, when the detected contact force starts to decrease, the force-position switching controller is switched from force control to position control, and the switching time interval is set in advance; wherein the time at which the contact force starts to decrease is time t3, based on the switching time interval and time t0, the time t4 is calculated, at which time the force-position switching controller is switched to position control;

[0044] The micro-injection needle remains in its current position under the position control mode of the force-position switching controller, and controls the micro-injector to complete the injection of exogenous substances;

[0045] The microinjection needle is removed from the cell in the position control mode of the force-position switching controller, and the cell microinjection task ends.

[0046] Beneficial Effects: Compared with existing technologies, this invention has the following significant advantages: The adaptive integral terminal sliding mode impedance force controller of this invention simultaneously possesses the finite-time convergence characteristics of terminal sliding mode control and the compliance force characteristics of impedance control. It is independent of environmental parameter information and can estimate the boundary of uncertain disturbances online through an adaptive law, thereby effectively enhancing the system's robustness to unknown cellular viscoelastic properties. The composite PID position controller designed in this invention, by combining feedback PID control and a feedforward fractional-order Bouc-Wen model, effectively suppresses rate-dependent and asymmetric hysteresis nonlinear effects. The dual Sigmoid function switching criterion designed in this invention enables a stable and smooth transition during switching, reducing switching chatter. The force-position switching controller of this invention provides accurate force and position tracking performance in each control mode, and still exhibits low chatter and cell damage even during multiple switching between different modes. Attached Figure Description

[0047] Figure 1 This is a flowchart of the design method of the present invention;

[0048] Figure 2 This is a schematic diagram of the force-position switching device of the present invention;

[0049] Figure 3 This is a timing diagram of the control mode of the force-position switching controller of the present invention;

[0050] Figure 4 This is a structural block diagram of the force-position switching controller of the present invention;

[0051] Figure 5 This is the trajectory tracking curve of the micro-injection needle in the force control mode of the force-position switching controller in an embodiment of the present invention;

[0052] Figure 6 This is the trajectory tracking curve of the micro-injection needle in the position control mode of the force-position switching controller in an embodiment of the present invention;

[0053] Figure 7 This is the trajectory tracking curve of the micro-injection needle under the action of the force-position switching controller in the embodiment of the present invention. Detailed Implementation

[0054] The technical solution of the present invention will be further described below with reference to the accompanying drawings.

[0055] Example 1

[0056] This invention discloses a design method for a force-position switching controller of a piezoelectrically driven cell microinjector, such as... Figure 1 As shown, it includes the following steps:

[0057] S1: Based on cell deformation and viscoelasticity, a dynamic model of the system describing the formation of the microinjector with the cell is established using a mass-spring-damper system.

[0058] The expression for the dynamic model is as follows:

[0059] ,

[0060] Where m represents the mass of the cell microinjector, c represents the damping of the cell microinjector, k represents the stiffness of the cell microinjector, and x represents the measured output displacement of the cell microinjector. Indicates the output speed of the cell microinjector. denoted by , b represents the output acceleration of the cell microinjector, 'b' represents the voltage coefficient, and 'u' represents the input voltage of the piezoelectric actuator. This represents the measured contact force between the cell microinjector and the cell membrane. This represents the lumped disturbance term. The lumped disturbance term includes hysteresis nonlinearity, dynamic model uncertainty, and external disturbances, and its rate of change is bounded, i.e. ,in The upper bound of the unknown perturbation, and It is a constant greater than zero.

[0061] In actual calculation It is obtained by calculating the first derivative of x. It is obtained by calculating the second derivative of x.

[0062] S2: An adaptive integral terminal sliding mode impedance controller is designed based on a dynamic model to suppress the influence of cell viscoelastic mechanical characteristics.

[0063] The design of the adaptive integral terminal sliding mode impedance controller follows these steps:

[0064] S21: A nonlinear Hunt-Crossley model was used to establish an HC model to describe the viscoelastic mechanical characteristics of cells, and the HC model was used to characterize the contact force between the cell microinjector and the cell membrane. .

[0065] The expression for the HC model is as follows:

[0066] ,

[0067] in Represents the stiffness coefficient of the cell. denoted by , where n represents the damping coefficient of the cell, and n represents a constant greater than zero.

[0068] Because cells exhibit nonlinear viscoelastic mechanical properties, it is difficult to describe the relationship between cell contact forces and deformation using traditional linear models such as the Maxwell model and the Kelvin-Voigt model. The HC model, by employing a nonlinear model expression, can accurately describe the nonlinear viscoelastic process; therefore, the HC model is chosen to describe the nonlinear viscoelastic mechanical properties of cells, a microscale object.

[0069] S22: When the cell microinjector comes into contact with the cell and the cell membrane no longer deforms, the cell is said to have reached steady state. Let the position of the cell at the point of steady state be the equilibrium position. The cells are in a state of equilibrium. Let the force output by the adaptive integral terminal sliding mode impedance controller be the desired force. Using Taylor's formula Expanding the HC model yields the HC model used to describe contact forces. With Expectation The expansion of .

[0070] According to the Taylor expansion formula, The corresponding first-order linearized HC model has the following expression:

[0071] .

[0072] exist The corresponding expected force The calculation is performed using the HC primitive expression as follows:

[0073] ,

[0074] In the formula Therefore, we can further obtain the following relationship:

[0075] , , Substituting the three obtained relations into the first-order linearized HC model and simplifying, we obtain the final expansion of the linearized HC model as follows:

[0076] ,

[0077] in , The higher-order terms ignored in the expansion of the HC model are regarded as the modeling error of the dynamic model, and the modeling error is included in the lumped disturbance term. It is then processed by the adaptive integral terminal sliding mode impedance controller, that is, by step S23.

[0078] S23: When the cell microinjector comes into contact with the cell, the force exerted by the cell membrane on the cell microinjector in the opposite direction is the impedance. When the cell reaches a steady state, the adaptive integral terminal sliding mode impedance force controller adjusts the contact force by adjusting the desired impedance between the cell microinjector and the cell, and sets the desired impedance equation based on the idea of ​​generalized impedance control.

[0079] The expression for the desired impedance equation is as follows:

[0080] ,

[0081] ,

[0082] ,

[0083] like Figure 4 As shown, where This indicates the desired position, where the desired position refers to the desired output force of the adaptive integral terminal sliding mode impedance controller. At that time, the theoretical output displacement of the cell microinjector; This represents the position tracking error, which is the difference between the measured output displacement x of the cell microinjector and the expected position. The difference; The force tracking error refers to the measured contact force. With Expectation The difference; , , , The target parameter represents the generalized impedance.

[0084] S24: Calculate the expected viscoelastic impedance dynamics model when the cell reaches steady state based on the expansion of the HC model and the expected impedance equation. Calculate the steady-state force error equation corresponding to the cell reaching steady state based on the viscoelastic impedance dynamics model. Calculate the convergence condition when the steady-state force error converges to zero based on the steady-state force error equation. Update the expected impedance equation in step S23 based on the convergence condition to obtain the updated expected impedance equation.

[0085] The expression for the viscoelastic impedance dynamics model is as follows: The expression for the steady-state force error equation is: .

[0086] The derivation of the steady-state force error equation is as follows: Based on the expression of the viscoelastic impedance dynamics model above, it can be seen that when the cell is in a steady state... , Therefore, there is

[0087] ,

[0088] After simplifying the above equation, we can obtain

[0089] ,

[0090] In the above formula This represents the steady-state position error. Combined with the expression for the desired impedance equation... The steady-state force error can then be obtained:

[0091] .

[0092] Based on the steady-state force error equation, it can be derived that, to ensure the steady-state force error of the closed-loop system of the adaptive integral terminal sliding mode impedance force controller converges to zero, the following must be satisfied: or When satisfied At this time, the desired position needs to be calculated in advance. The trajectory is used to calculate the desired position. It is necessary to accurately obtain the HC model parameters , , n, and these parameters are difficult to obtain accurately. Therefore, screening As a condition for the steady-state force error to converge to zero, i.e., screening This serves as a condition for ensuring the desired steady state.

[0093] Conditions Substituting the desired impedance equation from step S23, we obtain the updated desired impedance equation. .

[0094] S25: Based on the updated desired impedance equation, design an auxiliary variable g for establishing the terminal sliding mode of the adaptive integral terminal sliding mode impedance controller. The auxiliary variable g is an intermediate variable in the process of establishing the terminal sliding mode.

[0095] The formula for calculating the auxiliary variable g is: ,in express The filtered force tracking error. The filtering method involves using a first-order filter. Perform filtering, and the expression for the first-order filter is: right Perform filtering processing, where for The first derivative, , .

[0096] The adaptive integrator-terminal sliding mode impedance controller designed in this invention exhibits strong stability, meaning it can converge to zero. The derivation process for the adaptive integrator-terminal sliding mode impedance controller converging to zero is as follows:

[0097] Theoretically, the left and right sides of the updated expected impedance equation are equal, but in reality they are not equal. The difference between them is defined as the impedance error. The formula for calculating impedance error is as follows:

[0098] .

[0099] Substitute the auxiliary variable g into the impedance error The calculation formula is used to obtain the updated impedance error. The calculation formula is obtained by taking the first derivative with respect to the auxiliary variable g. and will and Substitution The updated impedance error is obtained. Calculation formula .

[0100] To ensure impedance error Converging to zero is equivalent to the auxiliary variable g converging to zero under the action of an adaptive integral terminal sliding mode impedance controller.

[0101] S26: Based on the auxiliary variable g in step S25, design the integral terminal sliding surface of the adaptive integral terminal sliding mode impedance controller.

[0102] The sliding surface expression for the integral-type terminal sliding mode is as follows:

[0103] ,

[0104] Where k1, k2 and It is a constant parameter, and , , , Using this integral-type terminal sliding mode, the impedance error... It can converge to zero within a finite amount of time.

[0105] Compared to traditional linear sliding surfaces, such as The advantage of the sliding mode in this invention lies in its use of a nonlinear terminal sliding manifold, which ensures that the impedance error converges to zero within a finite time, thus improving the dynamic response capability of the control system. Furthermore, the auxiliary variable g in the designed sliding surface contains... for The filtered force tracking error, whereas traditional sliding mode directly uses the original force tracking error. Integrating this signal can lead to the accumulation and amplification of force measurement noise, causing saturation or even instability in the control system.

[0106] The proof that the designed sliding surface converges in finite time is as follows:

[0107] Consider the following Lyapunov function: Taking the derivative of this expression with respect to time, we get Based on the defined sliding surface function, and let... You can get Substituting this equation into the first derivative of the Lyapunov function, we get:

[0108]

[0109] The above equation can be further rewritten as: ,in Therefore, convergence will occur within the following finite timeframe:

[0110]

[0111] In the formula, for The initial value.

[0112] S27: Based on the integral terminal sliding surface in step S26, select the state variable. .

[0113] State variables The expression is Where 's' refers to the sliding surface of the integral terminal sliding mode. The first derivative of s, and the state variable The following relationship must be satisfied: .

[0114] To complete the design of an adaptive integrator terminal sliding mode impedance controller and make the sliding mode function and its integral approach zero, a positive definite Lyapunov function is first defined. as follows:

[0115]

[0116] In the formula , .

[0117] Taking the derivative of the above equation with respect to time, we can obtain... .

[0118] S28: Define state variables The expected value is ,and ,in , , where are constant parameters. The parameter is time-varying, and , , And state variables Compared with expectations The error between them is z. .

[0119] Among them, state variables Expected value This was derived by working backwards from the stability proof, and the stability proof process is as follows: The first derivative is obtained by taking the derivative. ,Will Substitution get ;

[0120] Furthermore, we define the Lyapunov function. as follows:

[0121]

[0122] In the formula, , .

[0123] right Differentiating with respect to time yields... .

[0124] S29: Based on dynamic model, auxiliary variable g, and state variable The adaptive integral terminal sliding mode impedance controller is designed as follows:

[0125] ,

[0126] in , , For robustness, It is the upper bound of the unknown disturbance. The estimated value, and Determined by the following adaptive law , where parameters .and and It is a constant parameter.

[0127] To ensure the stability of the designed adaptive integral terminal sliding mode impedance controller, a Lyapunov function is defined. as follows:

[0128]

[0129] in Indicates the upper bound of the unknown perturbation. The estimation error.

[0130] right Regarding the time derivative, and combining it with the adaptive law, we can obtain:

[0131] ,

[0132] Will Substitution We can obtain:

[0133] ,

[0134] To calculate the above formula This term, firstly, is obtained by differentiating with respect to the auxiliary variable g. And combined with dynamic models and state variables From the expression, we can derive:

[0135] ,

[0136] Then, the designed adaptive integral terminal sliding mode impedance controller Substituting u into the above formula, we get:

[0137] ,

[0138] That is Thus, we obtain the following equation: ,

[0139] because and According to the Lyapunov stability principle, the designed adaptive integral terminal sliding mode impedance controller is stable.

[0140] S3: Select a feedforward compensator and feedback control law to design a composite PID position controller to suppress piezoelectric hysteresis nonlinearity. ,in This indicates a feedforward compensator used to suppress nonlinear hysteresis in piezoelectrically driven microinjectors; It is a feedback control law that handles unmodeled dynamics, external disturbances, and residual hysteresis compensation errors.

[0141] The feedforward compensator in step S3 is a feedforward compensator based on the fractional-order Bouc-Wen model.

[0142] The reason for choosing the fractional-order Bouc-Wen model for the feedforward compensator is its advantage in describing asymmetric and rate-dependent behavior. The expression for the feedforward compensator described in step S3 is as follows: ,in As an auxiliary lagged variable, and , where parameters , , , , , , Used to determine the shape of the hysteresis loop, and , , And operators This represents the Caputo fractional derivative.

[0143] The feedback control law mentioned in step S3 adopts PID control. ,in For proportional control gain, For integral control gain, This is the differential control gain.

[0144] The design of the composite PID position controller aims to combine the advantages of a feedforward compensator based on a fractional-order Bouc-Wen model and a PID feedback controller. The fractional-order Bouc-Wen model is used as the feedforward compensator to suppress the nonlinear rate-dependent hysteresis effect in the piezoelectric actuator; while PID control is used as the feedback controller to handle unmodeled dynamics, external disturbances, and residual hysteresis compensation errors. Because piezoelectric microinjectors exhibit complex nonlinear disturbances, while a single PID control can suppress external disturbances through feedback adjustment, it struggles to effectively suppress nonlinear rate-dependent hysteresis. A single feedforward compensator can only handle hysteresis nonlinearity, and its control accuracy depends on the accuracy of the hysteresis model, thus failing to achieve satisfactory performance and struggling to suppress other external disturbances. Combining the two approaches helps to completely suppress nonlinear disturbances in the piezoelectric-driven microinjector system and improve position tracking accuracy.

[0145] S4: Design a switching function for switching based on the double Sigmoid function switching criterion.

[0146] Switching between a PID position controller and an adaptive integral terminal sliding mode impedance controller can cause jitter in the control input (the input voltage of the piezoelectric drive), resulting in additional mechanical damage to the cells. To ensure a smooth transition between the two control modes, a switching function is designed based on a dual Sigmoid function switching criterion. ,in , , Indicates the current time; This indicates the moment when the force-position controller switches during microinjection. The cell microinjector begins to move at a constant speed from the preset position until it contacts the cell. Position control is applied during the constant-speed movement of the cell microinjector towards the cell, and the moment of contact between the cell microinjector and the cell is... ; The timing at which the cell microinjector begins to switch from position control to force control is preset with a time interval for this switch. This indicates the initial moment when the control has switched from position control to force control; This indicates the moment when the cell membrane is penetrated by the cell microinjector. At a certain moment, the cell microinjector switches from force control to position control, with the time interval for switching between force control and position control preset. This indicates the initial moment when the control has switched from force control to position control; in practical applications, , , , These four time points were obtained through multiple trials, and the average value of these trials was used as the empirical value for each time point. Parameters This is used to adjust the shape of the switching function. A value greater than 0 indicates a steeper slope in the switching curve, while a smaller value indicates a shallower slope. The derivative of the above function expression shows that it remains mathematically continuous, thus demonstrating that this criterion guarantees smooth switching.

[0147] By employing a dual Sigmoid function switching criterion, a smooth transition between the two control modes of the force-position switching controller is achieved, while also compensating for hysteresis and viscoelastic effects, thereby reducing cell damage during microinjection.

[0148] S5: Combining the adaptive integral terminal sliding mode impedance controller, PID position controller, and switching function, the final force-position switching control law is calculated as follows: , , These represent the force controller in step S2. The weighting coefficients and the position controller in step S3 The weighting coefficients. And .

[0149] Example 2

[0150] This invention discloses a force-position switching device for a piezoelectrically driven cell microinjector, such as... Figure 2As shown, the device includes a piezoelectric actuator 1, a force-position switching controller, a connecting rod 3, a micro-force sensor 4, and a micro-injection needle 5. The force-position switching controller is electrically connected to the piezoelectric actuator 1 and controls its output. The piezoelectric actuator 1 outputs displacement to provide the stroke required for cell microinjection. The connecting rod 3 is connected to the output end of the piezoelectric actuator 1 via a connector. The connector can be selected according to actual conditions, preferably a bolt connection, but is not limited to a bolt connection. The micro-force sensor 4 is connected to the other end of the connecting rod 3 via another connector. The micro-injection needle 5 is fixedly mounted on the micro-force sensor 4, and the micro-force sensor 4 is used to measure the contact force between the micro-injection needle 5 and the cell. The micro-force sensor 4 is also electrically connected to an external displacement sensor that measures its output displacement.

[0151] Preferably, the piezoelectric actuator 1 is a flexible amplification mechanism with amplified output displacement function.

[0152] Example 3

[0153] This invention discloses an injection method for a piezoelectrically driven force-position switching device for cell microinjectors, such as... Figure 3 As shown, it includes the following steps:

[0154] Switch the force-position switching controller to position control and drive the microinjection needle to the preset position, which is the designated puncture position for the target cell.

[0155] The microinjection needle moves at a constant speed towards the target cell under the position control mode of the force-position switching controller. A micro-force sensor detects the contact force between the microinjection needle and the target cell membrane in real time. When the contact force exceeds a preset threshold, the force-position switching controller switches from position control to force control, with a pre-set switching time interval. The moment when the contact force exceeds the preset threshold is... Time, based on the switching time interval and Time calculation obtained time, The force-position switching controller switches to force control. The process of the microinjection needle moving at a constant speed from the preset position towards the target cell is recorded as the approach phase. The speed at which the microinjection needle moves towards the target cell is set according to the actual situation, and the approach phase ranges from 0 to... time.

[0156] The microinjection needle contacts the target cell membrane in force-position control mode of the force-position switching controller. A micro-force sensor detects the contact force between the microinjection needle and the target cell membrane in real time. When the detected contact force begins to decrease, the force-position switching controller switches from force control to position control, with a pre-set switching time interval. The start time of the contact force decrease is... Time; based on switching time interval and Time calculation obtained time, The force-position switching controller switches to position control. The process from the microinjection needle contacting the target cell membrane to penetrating the target cell membrane is recorded as the puncture phase, and the puncture phase is... Time to time.

[0157] In practical applications, under uniformly determined preset positions, the speed at which the microinjection needle moves uniformly towards the target cell in the position control mode of the force-position switching controller, and the switching time interval, the results were determined through multiple experiments. , , , These four empirical values ​​are used as the switching function in step S4 of Example 1.

[0158] The microinjection needle remains in its current position under the position control mode of the force-position switching controller, and controls the microinjector to complete the injection of exogenous substances. The microinjection process is recorded as the injection phase. The injection time required to inject the exogenous substance is set according to the actual situation, based on the injection time... Time calculation obtained At that time, and the injection phase is Time to time.

[0159] The microinjection needle removes the cell under the position control mode of the force-position switching controller, ending the cell microinjection task. The process of the microinjection needle removing the cell is recorded as the retraction phase. The removal time required is set according to the actual situation, based on the removal time... Time calculation obtained At that time, and the injection phase is Time to time.

[0160] Example 4

[0161] This invention discloses a design method for a force-position switching controller of a piezoelectrically driven cell microinjector. An example of its application in a cell microinjection experiment is given. Steps S1-S5 of Example 1 are performed to conduct the cell microinjection experiment. The results of the cell microinjection experiment are as follows: Figures 5 to 7 As shown. By Figure 5 and Figure 6 It can be seen that when the piezoelectrically driven micro-injector is in either the force control mode or the position control mode of the force-position switching controller, it can achieve high-precision trajectory tracking performance, which verifies the effectiveness of the force-position switching controller designed in this invention. Figure 7The figure shows the force, position, and control voltage time response curves of two control modes under the action of the designed force-position switching controller during the complete cell microinjection process. As can be seen from the figure, the force-position switching controller can still maintain stable tracking performance when multiple switching occurs. The control voltage signal output by the controller only generates small switching jitter, which has little impact on the output position and force error, thereby reducing cell damage. This verifies that the design method of the force-position switching controller of the present invention can complete the cell microinjection task well, with stable performance and small jitter during switching.

Claims

1. A design method for a force-position switching controller of a piezoelectrically driven cell microinjector, characterized in that: Includes the following steps, S1: Based on the deformability and viscoelasticity of cells, a dynamic model of the system describing the formation of microinjectors with cells is established using a mass-spring-damper system; S2: Based on a dynamic model, an adaptive integral terminal sliding mode impedance controller is designed to suppress the influence of cellular viscoelastic mechanical characteristics; the steps for designing the adaptive integral terminal sliding mode impedance controller to suppress the influence of cellular viscoelastic mechanical characteristics are as follows: S21: A nonlinear Hunt-Crossley model was used to establish an HC model to describe the viscoelastic mechanical characteristics of cells, and the HC model was used to characterize the contact force between the cell microinjector and the cell membrane. ; S22: When the cell microinjector comes into contact with the cell and the cell membrane no longer deforms, the cell is said to have reached steady state. Let the position of the cell at the point of steady state be the equilibrium position. The cells are in a state of equilibrium. Let the force output by the adaptive integral terminal sliding mode impedance controller be the desired force. Using Taylor's formula Expanding the HC model yields the HC model used to describe contact forces. With Expectation The expansion of; S23: When the cell microinjector comes into contact with the cell, the force exerted by the cell membrane on the cell microinjector in the opposite direction is the impedance. When the cell reaches a steady state, the adaptive integral terminal sliding mode impedance force controller adjusts the contact force by adjusting the desired impedance between the cell microinjector and the cell, and sets the desired impedance equation based on the idea of ​​generalized impedance control. S24: Calculate the expected viscoelastic impedance dynamics model when the cell reaches steady state based on the expansion of the HC model and the expected impedance equation, and calculate the steady-state force error equation corresponding to the cell reaching steady state based on the viscoelastic impedance dynamics model. The convergence condition when the steady-state force error converges to zero is calculated based on the steady-state force error equation. The desired impedance equation in step S23 is updated based on the convergence condition to obtain the updated desired impedance equation. S25: Design an auxiliary variable g for the terminal sliding mode of the adaptive integral terminal sliding mode impedance controller by combining the updated desired impedance equation; S26: Design the integral terminal sliding surface of the adaptive integral terminal sliding mode impedance controller based on the auxiliary variable g in step S25; S27: Based on the integral terminal sliding surface in step S26, select the state variable. ;and Where 's' refers to the sliding surface of the integral terminal sliding mode. The first derivative of s; S28: Define state variables The expected value is ,and ,in , , where are constant parameters. The parameter is time-varying, and , , And state variables Compared with expectations The error between them is z; S29: Based on dynamic model, auxiliary variable g, and state variable Thus, the final adaptive integral terminal sliding mode impedance controller is obtained; S3: Select a feedforward compensator and feedback control law to design a composite PID position controller to suppress piezoelectric hysteresis nonlinearity; S4: A switching function based on a dual Sigmoid function switching criterion is designed for switching between an adaptive integral terminal sliding mode impedance controller and a composite PID position controller; where the switching function is... ,in , , This indicates the current moment; the cell microinjector begins its uniform delivery from a preset position until it contacts the cell. The uniform movement of the cell microinjector towards the cell is position-controlled, and the moment of contact between the cell microinjector and the cell is [the current moment]. ; The timing at which the cell microinjector begins to switch from position control to force control is preset with a time interval for this switch. This indicates the initial moment when the control has switched from position control to force control; This indicates the moment when the cell membrane is penetrated by the cell microinjector. At a certain moment, the cell microinjector switches from force control to position control, with the time interval for switching between force control and position control preset. This indicates the initial moment when the control has switched from force control to position control; parameters Used to adjust the shape of the switching function; its value is proportional to the switching rate. S5: Combining the adaptive integral terminal sliding mode impedance force controller, PID position controller and switching function, the switching control law of the final force-position switching controller is calculated.

2. The design method of the force-position switching controller for the piezoelectrically driven cell microinjector according to claim 1, characterized in that: The expression for the dynamic model described in step S1 is as follows: ， Where m represents the mass of the cell microinjector, c represents the damping of the cell microinjector, k represents the stiffness of the cell microinjector, and x represents the measured output displacement of the cell microinjector. Indicates the output speed of the cell microinjector. denoted by , b represents the output acceleration of the cell microinjector, 'b' represents the voltage coefficient, and 'u' represents the input voltage of the piezoelectric actuator. This represents the measured contact force between the cell microinjector and the cell membrane. This represents the lumped disturbance term.

3. The design method of the force-position switching controller for the piezoelectrically driven cell microinjector according to claim 2, characterized in that: The expression for the HC model in step S21 is: ,in Represents the stiffness coefficient of the cell. This represents the damping coefficient of the cell, where n represents a constant greater than zero; The expansion of the HC model in step S22 is as follows: ,in , ; The expression for the desired impedance equation in step S23 is: ,in Indicates the desired location; Indicates position tracking error. ; Indicates force tracking error, ; , , , The target parameter represents the generalized impedance; The expression for the viscoelastic impedance dynamics model in step S24 is as follows: ； When cells are in a homeostatic state , , , that is ,in For steady-state position error; combined with the desired impedance equation and steady-state position error The steady-state force error was calculated. And steady-state force error The expression is Based on this expression, the convergence condition is determined as follows: The updated expected impedance equation is then: ; The expression for the auxiliary variable g in step S25 is: ,in This indicates that a first-order filter is used for... The filtered force tracking error, and the expression for the first-order filter is: ,in for First derivative, , ; The sliding surface expression for the integral terminal sliding mode in step S26 is: Where k1, k2 and It is a constant parameter, and , , , ; The expression for the error z in step S28 is: ; The expression for the adaptive integral terminal sliding mode impedance controller in step S29 is as follows: ,in , , For robustness, It is the upper bound of the unknown disturbance. The estimated value, and , where parameters .

4. The design method of the force-position switching controller for the piezoelectrically driven cell microinjector according to claim 3, characterized in that: The feedforward compensator in step S3 is a feedforward compensator based on the fractional-order Bouc-Wen model, and the expression for this feedforward compensator is: ,in As an auxiliary lagged variable, and , where parameters , , , , , , Used to determine the shape of the hysteresis loop, and , , , This represents the Caputo fractional derivative.

5. The design method of the force-position switching controller for the piezoelectrically driven cell microinjector according to claim 4, characterized in that: The feedback control law in step S3 adopts PID control. ,in For proportional control gain, For integral control gain, This is the differential control gain.

6. The design method of the force-position switching controller for the piezoelectrically driven cell microinjector according to claim 5, characterized in that: The switching control law of the force-position switching controller in step S5 is as follows: .

7. A force-position switching device for a piezoelectrically driven cell microinjector, characterized in that: The design method of the force-position switching controller of the piezoelectrically driven cell microinjector as described in claim 1 includes a piezoelectric actuator, a force-position switching controller for controlling and electrically connecting the output end of the piezoelectric actuator, a connecting rod connected to the output end of the piezoelectric actuator via a connector, a micro-force sensor connected to the other end of the connecting rod via another connector and used for measuring contact force, and a micro-injection needle installed at the end of the micro-force sensor, wherein the micro-force sensor is electrically connected to an external displacement sensor for measuring its output displacement.

8. An injection method for a force-position switching device of a piezoelectrically driven cell microinjector according to claim 7, characterized in that: Includes the following steps, Switch the force-position switching controller to position control and drive the microinjection needle to the preset position; The microinjection needle moves at a constant speed towards the target cell under the position control mode of the force-position switching controller. A micro-force sensor detects the contact force between the microinjection needle and the target cell membrane in real time. When the contact force exceeds a preset threshold, the force-position switching controller switches from position control to force control, with a pre-set switching time interval. The moment when the contact force exceeds the preset threshold is... Time, based on the switching time interval and Time calculation obtained time, The force-position switching controller switches to force control at any time. The microinjection needle contacts the target cell membrane in force-position control mode of the force-position switching controller. A micro-force sensor detects the contact force between the microinjection needle and the target cell membrane in real time. When the detected contact force begins to decrease, the force-position switching controller switches from force control to position control, with a pre-set switching time interval. The start time of the contact force decrease is... Time; based on switching time interval and Time calculation obtained time, The force-position switching controller switches to position control at any time. The micro-injection needle remains in its current position under the position control mode of the force-position switching controller, and controls the micro-injector to complete the injection of exogenous substances; The microinjection needle is removed from the cell in the position control mode of the force-position switching controller, and the cell microinjection task ends.

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