Method for obtaining machining parameters of pH-magnetic micro-nano robot, pH-magnetic micro-nano robot and manufacturing method and application of pH-magnetic micro-nano robot

Abstract

The invention provides a method for acquiring machining parameters of a pH-magnetic micro-nano robot, the pH-magnetic micro-nano robot and a manufacturing method and application of the pH-magnetic micro-nano robot, and belongs to the technical field of micro-nano robots. The method comprises the following steps: carrying out theoretical modeling on a design model of the double-layer film holder to obtain a state matrix about curvature; the target model of the double-layer film holder is subjected to timoshe beam model modeling, and a target matrix about the curvature is obtained; and obtaining the machining parameters according to the state matrix about the curvature and the target matrix about the curvature. According to the method, the machining parameters of the double-layer film holder in the pH-magnetic micro-nano robot are obtained on the basis of theoretical modeling and reverse design, the trial and error processes are effectively reduced in the micro-nano robot preparation process, the time and the manufacturing cost are saved, and therefore the micro-nano robot can be accurately and efficiently prepared.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of micro-nano robots, in particular to a method for obtaining processing parameters of a pH-magnetic micro-nano robot, a pH-magnetic micro-nano robot, a manufacturing method and an application. BACKGROUND

[0002] Micro-nano robots have become a research object widely used in micro fields due to their limited movement ability and small size, especially in aspects of material delivery, minimally invasive surgery, cell operation, detection and diagnosis. At present, the energy supply of micro-nano robots mainly depends on internal biochemical reactions or external energy fields such as magnetic field, pH value, electric field or light field. However, the optimization process of processing parameters in the preparation process of micro-nano robots is complex, and the time and manufacturing cost are high. SUMMARY

[0003] The present application relates to the technical field of micro-nano robots, in particular to a method for obtaining processing parameters of a pH-magnetic micro-nano robot, a pH-magnetic micro-nano robot, a manufacturing method and an application.

[0004] In order to achieve the above-mentioned application purposes, the present application provides the following technical solutions: The present application provides a method for obtaining processing parameters of a double-layer film gripper in a pH-magnetic micro-nano robot, The double-layer film gripper comprises a first jaw body and a second jaw body, and the first jaw body and the second jaw body are in a ring structure when clamped. The double-layer film structure of the first jaw body and the second jaw body independently comprises a pH response layer and a non-pH response layer which is stacked on the inner surface of the pH response layer. The first jaw body and the second jaw body are expanded and bent inward to change into a clamped state under the action of pH stimulation from an initial state. The processing parameters comprise h and m, h = h1 + h2, and m = h1 / h2. h1 is the initial thickness of the pH response layer, and h2 is the initial thickness of the non-pH response layer. The method comprises the following steps: The design model of the double-layer film gripper is theoretically modeled to obtain a state matrix related to curvature. The design model of the double-layer film gripper corresponds to the initial state of the first jaw body and the second jaw body in the double-layer film gripper. The target model of the double-layer film gripper is modeled by the Timoshenko beam model to obtain a target matrix related to curvature. The target model of the double-layer film gripper corresponds to the clamped state of the first jaw body and the second jaw body bent inward under the action of pH stimulation. obtaining the processing parameter according to the state matrix about curvature and the target matrix about curvature; The state matrix about curvature is expressed by formula 7: Formula 7; Wherein k1 is the curvature of the corresponding arc of the first jaw or the second jaw clamping state, R1 is the curvature radius of the corresponding arc of the first jaw or the second jaw clamping state, k0 is the curvature of the corresponding arc of the first jaw or the second jaw initial state, θ is the central angle of the corresponding arc of the first jaw or the second jaw initial state, H is the distance between the bottom end of the first jaw or the second jaw and the center of symmetry. The target matrix about curvature is expressed by formula 11: Formula 11; Wherein R0 is the curvature radius of the corresponding arc of the first jaw or the second jaw initial state, λ1 is the expansion rate of the pH responsive layer, λ2 is the expansion rate of the non-pH responsive layer, and n is the ratio of the Young's modulus of the pH responsive layer to the Young's modulus of the non-pH responsive layer.

[0005] Preferably, the formula 7 is obtained according to formula 1-6: Formula 1; Formula 2; Formula 3; Formula 4; Formula 5; Formula 6; Wherein The arc length of the corresponding arc of the first jaw or the second jaw, L is the chord length of the corresponding arc of the first jaw or the second jaw initial state, y0 is the vertical distance between the center of the corresponding arc of the first jaw or the second jaw clamping state and the bottom end, and y is the vertical distance between the top point and the bottom end of the corresponding arc of the first jaw or the second jaw clamping state. The formula 11 is obtained according to formula 8-10: Formula 8; Formula 9; Formula 10; Wherein P1 is the tension of the pH responsive layer, P2 is the tension of the non-pH responsive layer, M1 is the bending moment of the pH responsive layer, M2 is the bending moment of the non-pH responsive layer, E1 is the Young's modulus of the pH responsive layer, E2 is the Young's modulus of the non-pH responsive layer, I1 is the moment of inertia of the pH responsive layer, and I2 is the moment of inertia of the non-pH responsive layer.

[0006] The application provides a system for obtaining a processing parameter of a double-layer membrane gripper in a pH-magnetic micro-nano robot, comprising: a theoretical modeling module configured to perform theoretical modeling on a design model of the double-layer membrane gripper to obtain a state matrix related to curvature; the design model of the double-layer membrane gripper corresponds to an initial state of a first gripper body and a second gripper body in the double-layer membrane gripper; a Timoshenko beam modeling module configured to perform Timoshenko beam modeling on a target model of the double-layer membrane gripper to obtain a target matrix related to curvature; the target model of the double-layer membrane gripper corresponds to a clamping state in which the first gripper body and the second gripper body in the double-layer membrane gripper are bent inward under the action of pH stimulation; a data processing and output module configured to perform data processing and output on the state matrix related to curvature and the target matrix related to curvature to obtain the processing parameters h and m in the method described in the above technical solution.

[0007] The application provides a computer readable storage medium storing a computer program or instructions, which, when executed, cause a computer to perform the method described in the above technical solution.

[0008] The application provides a manufacturing method of a double-layer membrane gripper in a pH-magnetic micro-nano robot, comprising the following steps: a non-pH responsive layer with an initial thickness of h2 is obtained by sequentially performing first printing and first developing on a photoresist; a pH responsive layer with an initial thickness of h1 is formed on the surface of the non-pH responsive layer by sequentially performing second printing and second developing on the pH hydrogel, thereby obtaining the double-layer membrane gripper; The h1 and h2 are calculated by the processing parameters obtained by the method described in the above technical solution.

[0009] Preferably, the raw materials for preparing the pH hydrogel include N-isopropyl acrylamide, acrylic acid, tetraethyl Michler's ketone and dipentaerythritol pentaacrylate.

[0010] Preferably, the photoresist is IP-L photoresist.

[0011] Preferably, the developing reagent used in the first developing and the second developing is isopropyl alcohol.

[0012] The application provides a pH-magnetic micro-nano robot, which comprises a magnetic main body and a double-layer film holder, the double-layer film holder comprises a first clamp body and a second clamp body, the bottom end of the first clamp body and the bottom end of the second clamp body are connected with the magnetic main body; the first clamp body and the second clamp body are in a ring structure when clamped, the double-layer film structure of the first clamp body and the second clamp body independently comprises a pH-responsive layer and a non-pH-responsive layer which is arranged on the inner surface of the pH-responsive layer in a laminated mode; the material of the pH-responsive layer is a pH hydrogel; the material of the non-pH-responsive layer is photoresist; the material of the magnetic main body is a magnetic hydrogel, and the magnetic hydrogel comprises a NIPAM hydrogel and magnetic powder dispersed in the NIPAM hydrogel.

[0013] The application provides an application of the pH-magnetic micro-nano robot in preparation of a cell micro-operation system or a drug delivery system.

[0014] Beneficial effects: the processing parameters of the double-layer film holder in the pH-magnetic micro-nano robot are obtained based on theoretical modeling and reverse design, the in-plane bending deformation caused by the expansion of the pH hydrogel (i.e. the expansion of the pH hydrogel under the stimulation of the pH field) is considered for the sake of simplicity, therefore, the mapping of the double-layer film holder from the driving space to the conformal space can be described by using the Timoshenko bending theory (Timoshenko beam model), the relationship between the two is established by combining the theoretical modeling, and the optimal processing parameters are obtained. The results of the embodiments show that the design and trial time can be greatly reduced by using the method, and the optimal processing parameters can be directly obtained, and the robot with a size of 100 mu m level can be prepared.

[0015] In addition, the pH-magnetic micro-nano robot in the application is a kind of multifunctional response micro-nano robot, which can be precisely controlled in various environments through the dual control of pH responsiveness and magnetic field driving, solves the limitation of the function integration of the traditional micro-nano robot, and expands the application range. BRIEF DESCRIPTION OF DRAWINGS

[0016] Figure 1 It is a structural schematic diagram of the pH-magnetic micro-nano robot in the embodiment; Figure 2 It is a preparation process flow schematic diagram of the pH-magnetic micro-nano robot in the embodiment; Figure 3 It is a process schematic diagram of obtaining the processing parameters of the pH-magnetic micro-nano robot based on theoretical modeling and reverse design in the application; Figure 4 It is a pH hydrogel polymerization principle schematic diagram in the embodiment; Figure 5An optical image (TIE inverted microscope) of the pH-magnetic micro robot in the example; Figure 6 An optical image (TIE inverted microscope, scale bar: 10 μm) of the gradual merging of the double-layer film gripper from the initial state in the example. DETAILED DESCRIPTION

[0017] The application provides a method for obtaining processing parameters of a pH-magnetic micro-nano robot based on theoretical modeling and reverse design, The double-layer film gripper comprises a first gripper body and a second gripper body, the first gripper body and the second gripper body are in a ring structure when clamped, and the double-layer film structure of the first gripper body and the second gripper body independently comprises a pH-responsive layer and a non-pH-responsive layer which is arranged on the inner surface of the pH-responsive layer in a stack, and the first gripper body and the second gripper body are transformed into a clamped state by inward bending under the action of pH stimulation from an initial state; The processing parameters comprise h and m, the h = h1 + h2, the m = h1 / h2, the h1 is the initial thickness of the pH-responsive layer, and the h2 is the initial thickness of the non-pH-responsive layer; The method comprises the following steps: The design model of the double-layer film gripper is theoretically modeled to obtain a state matrix related to curvature; the design model of the double-layer film gripper corresponds to the initial state of the first gripper body and the second gripper body in the double-layer film gripper; The target model of the double-layer film gripper is modeled according to the Timoshenko beam model to obtain a target matrix related to curvature; the target model of the double-layer film gripper corresponds to the clamped state of the first gripper body and the second gripper body in the double-layer film gripper which is inward bent under the action of pH stimulation; The processing parameters are obtained according to the state matrix related to curvature and the target matrix related to curvature; The state matrix related to curvature is expressed by formula 7: Formula 7; Wherein k1 is the curvature of the corresponding arc of the clamped state of the first gripper body or the second gripper body, R1 is the curvature radius of the corresponding arc of the clamped state of the first gripper body or the second gripper body, k0 is the curvature of the corresponding arc of the initial state of the first gripper body or the second gripper body, θ is the central angle of the corresponding arc of the initial state of the first gripper body or the second gripper body, and H is the distance between the bottom end of the first gripper body or the second gripper body and the center of symmetry; The target matrix related to curvature is expressed by formula 11: Formula 11; wherein R0 is the radius of curvature of the corresponding arc of the first jaw or the second jaw in the initial state, λ1 is the expansion rate of the pH-responsive layer, λ2 is the expansion rate of the non-pH-responsive layer, and n is the ratio of the Young's modulus of the pH-responsive layer to the Young's modulus of the non-pH-responsive layer.

[0018] In the present application, a state matrix about curvature is obtained by theoretically modeling the design model of the double-layer film holder, a target matrix about curvature is obtained by modeling the target model of the double-layer film holder into a Timoshenko beam model, and the output value h and m are obtained by solving the two together; the present application assumes that the arc length of the corresponding arc of the first jaw and the second jaw is constant during the entire bending process.

[0019] As an embodiment of the present application, the formula 7 is obtained according to the formula 1 to formula 6. The formula 1 is: The formula 2 is: The formula 3 is: The formula 4 is: The formula 5 is: The formula 6 is: wherein is the arc length of the corresponding arc of the first jaw or the second jaw, L is the chord length of the corresponding arc of the first jaw or the second jaw in the initial state, y0 is the vertical distance between the center and the bottom end of the corresponding arc of the first jaw or the second jaw in the clamped state, and y is the vertical distance between the top and the bottom end of the corresponding arc of the first jaw or the second jaw in the clamped state.

[0020] As an embodiment of the present application, the formula 11 is obtained according to the formula 8 to formula 10. The formula 8 is: The formula 9 is: The formula 10 is: wherein P1 is the tension of the pH-responsive layer, P2 is the tension of the non-pH-responsive layer, M1 is the bending moment of the pH-responsive layer, M2 is the bending moment of the non-pH-responsive layer, E1 is the Young's modulus of the pH-responsive layer, E2 is the Young's modulus of the non-pH-responsive layer, I1 is the moment of inertia of the pH-responsive layer, and I2 is the moment of inertia of the non-pH-responsive layer.

[0021] The application obtains the processing parameters of the double-layer film gripper by decoupling the head of the bionic Oryctes and theoretical modeling. Specifically, the double-layer film gripper is decoupled into a double-layer film, which is transformed from an initial state (i.e. a relaxed state) into a clamping state due to the directional bending caused by the stress mismatch between the pH-responsive layer and the non-pH-responsive layer. In the application, the double-layer film gripper is simplified into a mathematical model and a bending beam thermal expansion and contraction bending. Firstly, the curvature k1 of the corresponding arc in the clamping state is obtained by the geometric relationship, the arc length formula, the curvature formula, simultaneous equations 1, 2, 3, 4, 5 and 6 (formula 7); secondly, the in-plane bending deformation caused by the swelling of the pH hydrogel is considered by simplifying the hydrogel bending, and the curvature k1 of the corresponding arc in the clamping state is obtained by the Timoshenko beam formula, simultaneous equations 8, 9 and 10 (formula 11); and then the processing parameters m and h are obtained by combining the curvature k1 obtained from the mathematical model and the k1 obtained by using the Timoshenko beam model. That is, according to the formula 7 and the formula 11, the processing parameters m and h can be obtained under the condition that k0, θ, H, λ1, λ2 and n are known.

[0022] The application provides a system for obtaining the processing parameters of a double-layer film gripper in a pH-magnetic micro-nano robot, comprising: a theoretical modeling module configured to theoretically model a design model of the double-layer film gripper to obtain a state matrix related to curvature; the design model of the double-layer film gripper corresponding to an initial state of a first jaw body and a second jaw body in the double-layer film gripper; a Timoshenko beam model modeling module configured to model a target model of the double-layer film gripper by using the Timoshenko beam model to obtain a target matrix related to curvature; the target model of the double-layer film gripper corresponding to a clamping state in which the first jaw body and the second jaw body in the double-layer film gripper are bent inward under the action of pH stimulation; a data processing and output module configured to perform data processing and output on the state matrix related to curvature and the target matrix related to curvature to obtain the processing parameters h and m in the method of the above technical solution.

[0023] The application provides a computer readable storage medium storing a computer program or instructions, which, when executed, cause a computer to perform the method of the above technical solution.

[0024] The application provides a manufacturing method of a double-layer film gripper in a pH-magnetic micro-nano robot, comprising the following steps: a non-pH-responsive layer with an initial thickness of h2 is obtained by sequentially performing first printing and first developing on a photoresist; a pH-responsive layer with an initial thickness of h1 is formed on the surface of the non-pH-responsive layer by sequentially performing second printing and second developing on a pH hydrogel, so as to obtain the double-layer film gripper; The h1 and h2 are calculated by the processing parameters obtained by the method in the technical solution.

[0025] In the present application, if not otherwise specified, the raw materials used are all commercially available or prepared by methods well known to those skilled in the art.

[0026] As an embodiment of the present application, the pH-magnetic micro / nanorobot can be prepared on the surface of a glass sheet. Preferably, the glass sheet is pretreated before use, and the pretreatment comprises sequentially performing ultrasonic treatment, plasma hydrophilic treatment, and preparing a sacrificial layer. As an embodiment of the present application, the reagent used for ultrasonic treatment can be ethanol, specifically anhydrous ethanol, and the present application does not have special limitations on the conditions of the ultrasonic treatment. As an embodiment of the present application, the power of the plasma hydrophilic treatment can be 25-30 W, and the time can be 90-100 s. As an embodiment of the present application, the thickness of the sacrificial layer can be 450-500 nm; the reagent used for preparing the sacrificial layer can be a dextran aqueous solution, and the concentration of dextran in the dextran aqueous solution can be 10% (w / v); the method for preparing the sacrificial layer can be coating the dextran aqueous solution on the surface of the glass sheet and drying, thereby forming a sacrificial layer on the surface of the glass sheet; the coating method can be spin coating, and the drying method can be oven drying. The present application prepares a sacrificial layer, which facilitates subsequent peeling of the pH-magnetic micro / nanorobot.

[0027] The present application adopts photoresist to sequentially perform first printing and first developing to obtain a non-pH-responsive layer with an initial thickness of h2. As an embodiment of the present application, specifically, photoresist is added dropwise on the surface of the sacrificial layer on the glass sheet, and sequentially performs first printing and first developing to obtain a non-pH-responsive layer with an initial thickness of h2. As an embodiment of the present application, the photoresist can be IP-L photoresist; the first printing is two-photon printing using a 63X lens OIL mode, and a two-photon polymerization reaction occurs in the process; and the developing reagent used for the first developing is isopropyl alcohol. The present application does not have special limitations on the specific method of the first printing and the first developing, and a method well known to those skilled in the art can be used.

[0028] The pH hydrogel is used to form a pH response layer with an initial thickness of h1 on the surface of the non-pH response layer by second printing and second developing, so as to obtain the double-layer film holder. As an embodiment of the present application, the preparation raw materials of the pH hydrogel include N-isopropyl acrylamide (NIPAM), acrylic acid (AAc), tetraethyl methyl ketone (EMK) and dipentaerythritol pentaacrylate (DPEPA). In the embodiment of the present application, the preparation raw materials of the pH hydrogel specifically include: NIPAM 7.5-8 g, AAc 3.5-4 mL, polyvinylpyrrolidone (PVP) 0.70-0.75 g, ethyl lactate (EL) 4.5-5 mL, tetraethyl methyl ketone N,N-dimethylformamide (DMF) solution (abbreviated as EMK / DMF solution) 90-100 μL, triethanolamine (TEA) 0.35-0.4 mL and DPEPA 0.45-0.5 mL; the concentration of EMK in the EMK / DMF solution can be 18-20 wt%. As an embodiment of the present application, the developing reagent used in the second developing is isopropyl alcohol. The present application does not have special limitations on the specific ways of the second printing and the second developing, and the ways known to those skilled in the art can be used.

[0029] The present application provides a pH-magnetic micro-nano robot, which comprises a magnetic body and a double-layer film holder, the double-layer film holder comprises a first jaw body and a second jaw body, the bottom end of the first jaw body and the bottom end of the second jaw body are connected with the magnetic body; the first jaw body and the second jaw body are in a ring structure when clamped, and the double-layer film structure of the first jaw body and the second jaw body independently comprises a pH response layer and a non-pH response layer arranged on the inner surface of the pH response layer; the material of the pH response layer is a pH hydrogel; the material of the non-pH response layer is a photoresist; the material of the magnetic body is a magnetic hydrogel, which comprises a NIPAM hydrogel and magnetic powder dispersed in the NIPAM hydrogel.

[0030] In the present application, the second jaw body and the first jaw body are arranged in axial symmetry, and the size, structure and material are the same.

[0031] As an embodiment of the present application, the size of the pH-magnetic micro-nano robot can be 100 μm.

[0032] The pH-magnetic micro-nano robot can be held under the action of a pH field and be controlled under the action of a magnetic field (the magnetic body is a moving part), specifically, it can actively grasp target objects, anchor at target positions in the body, actively release the clamped objects, and can also load drugs and release drugs in the pores of hydrogels, so that it can be better applied in the fields of cell micro-operation or drug delivery. As an embodiment of the present application, the double-layer film gripper of the pH-magnetic micro-nano robot can be bent under the condition that the pH value is 11-12, and the pH value can be provided by a NaOH solution.

[0033] As an embodiment of the present application, the preparation method of the pH-magnetic micro-nano robot comprises the following steps: The magnetic body is obtained by sequentially performing third printing and third developing on the magnetic hydrogel, and then the double-layer film gripper is prepared according to the above method to obtain the pH-magnetic micro-nano robot.

[0034] As an embodiment of the present application, the surface of the sacrificial layer on the glass sheet is dripped with a magnetic hydrogel, and then a magnetic body is obtained by sequentially performing third printing and third developing. As an embodiment of the present application, the magnetic hydrogel comprises a NIPAM hydrogel and magnetic powder dispersed in the NIPAM hydrogel; the magnetic powder can be Fe3O4 powder, and the average particle size of the Fe3O4 powder can be 50 nm. As an embodiment of the present application, the raw materials for preparing the magnetic hydrogel comprise: NIPAM 3.8-4 g, N-isopropyl acrylamide polymer (p-NIPAM) 0.38-0.4 g, PVP 0.08-0.1 g, ethylene glycol (EG) 6.5-7 mL, EMK / DMF solution 90-100 μL, TEA 0.45-0.5 mL, DPEPA 0.38-0.4 mL, and Fe3O4 suspension 300-350 μL; the content of Fe3O4 in the Fe3O4 suspension is 8-10 wt%, and the average particle size of the Fe3O4 can be 50 nm; the present application controls the amount of solvent EG to be 6.5-7 mL, which can ensure that all components are completely dissolved, if the amount is less (such as 2.5-6 mL), complete dissolution cannot be achieved. As an embodiment of the present application, the developing reagent used for the third developing is isopropyl alcohol. The present application does not have special limitations on the specific ways of the third printing and the third developing, and the ways well known to those skilled in the art can be used.

[0035] In one embodiment of the present invention, after obtaining the magnetic body, photoresist is dropped onto the surface of the sacrificial layer on the glass slide and connected to the magnetic body. A non-pH responsive layer is obtained by sequentially performing a first printing and a first development. Then, pH hydrogel is dropped onto the surface of the non-pH responsive layer and connected to the magnetic body. A pH responsive layer is formed by sequentially performing a second printing and a second development, thus obtaining the pH-magnetic micro-nano robot.

[0036] In one embodiment of the present invention, after the second development, taking advantage of the property that the sacrificial layer is soluble in water, a Tween-20 aqueous solution with a volume fraction of 0.4~0.5% can be dropped onto the glass slide to dissolve the sacrificial layer and realize the release of the pH-magnetic micro-nano robot.

[0037] This invention provides the application of the pH-magnetic micro / nano robot described above in the preparation of cell micro-operating systems or drug delivery systems.

[0038] The technical solutions of this invention will be clearly and completely described below with reference to the embodiments thereof. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0039] Example 1 like Figure 1 As shown, in this embodiment, the pH-magnetic micro / nano robot includes a magnetic body and a double-layer membrane gripper. The double-layer membrane gripper includes a first clamp and a second clamp. The bottom ends of the first clamp and the second clamp are both connected to the magnetic body. When the first clamp and the second clamp are gripping each other, they form a ring-like structure. The double-layer membrane structure of the first clamp and the second clamp independently includes a pH-responsive layer and a non-pH-responsive layer stacked on the inner surface of the pH-responsive layer. The pH-responsive layer is made of pH hydrogel, and the non-pH-responsive layer is made of IP-L photoresist. The first clamp and the second clamp expand and bend inward under pH stimulation from the initial state.

[0040] like Figure 2 As shown, the manufacturing method of the pH-magnetic micro / nano robot in this embodiment includes the following steps: (1) The glass slide was ultrasonically treated with anhydrous ethanol, and then subjected to plasma hydrophilic treatment (the plasma cleaner was 30W and the treatment time was 100s). Then, a dextran aqueous solution (10%w / v) was spin-coated onto the surface of the glass slide and dried to obtain a sacrificial layer (500nm thick) on the surface of the glass slide, which facilitates the subsequent removal of the microrobot. (2) Magnetic hydrogel was dropped onto the surface of the sacrificial layer on the glass slide, coordinate calibration was performed, and the magnetic body was obtained after printing and development with isopropanol. The magnetic hydrogel was formulated as follows: 4g NIPAM, 0.4g p-NIPAM, 0.1g PVP, 6.5mL EG, 100μL EMK / DMF solution (EMK concentration is 20wt%), 0.5mL TEA, 0.4mL DPEPA and 350μL Fe3O4 suspension (Fe3O4 content is 10wt%, average particle size is 50nm) (the components of the magnetic hydrogel were purchased from Aladdin). (3) Obtaining the processing parameters of the pH-magnetic micro / nano robot based on theoretical modeling and reverse design (e.g.) Figure 3 As shown, where B and B1 represent the endpoints of the arc, and O and O1 represent the centers of the arc, the processing parameters include h and m, where h = h1 + h2, m = h1 / h2, h1 is the initial thickness of the pH-responsive layer, and h2 is the initial thickness of the non-pH-responsive layer; specifically, the design model of the double-layer membrane holder is theoretically modeled to obtain a state matrix about curvature (represented by Equation 7, which is obtained from Equations 1 to 6); the target model of the double-layer membrane holder is modeled using the Timoshenko beam model to obtain a target matrix about curvature (represented by Equation 11, which is obtained from Equations 8 to 10); the processing parameters are obtained based on the state matrix about curvature and the target matrix about curvature; IP-L photoresist (nanoscribe) was dropped onto the surface of the sacrificial layer on a glass slide and connected to the magnetic host. Two-photon printing (two-photon polymerization reaction) was performed using a 63X lens in OIL mode. After development with isopropanol, a non-pH responsive layer was obtained. A pH-responsive hydrogel was dropped onto the surface of the non-pH-responsive layer and attached to the magnetic substrate. Coordinate calibration was performed using alignment marks from the modeling process, followed by printing (as a polymerization reaction occurs, e.g.) Figure 4 As shown, the precursor solution, i.e., the pH hydrogel, undergoes a polymerization reaction under 405nm wavelength irradiation to form a cross-linked network. After development with isopropanol, a pH-responsive layer is obtained, thus forming a pH-responsive-non-pH-responsive bilayer membrane structure, resulting in a bilayer membrane holder. The pH hydrogel formulation is as follows: NIPAM 8g, AAc 4mL, PVP 0.75g, EL 5mL, EMK / DMF solution (EMK concentration is 20wt%) 100μL, TEA 0.4mL, DPEPA 0.5mL (the components of the pH hydrogel were purchased from Aladdin). (4) Taking advantage of the property that the sacrificial layer is soluble in water, a 0.5% Tween-20 aqueous solution was added to the glass slide to dissolve the sacrificial layer and realize the release of the pH-magnetic micro-nano robot.

[0041] Figure 5 For the optical diagram of the pH-magnetic micro robot in the embodiment, specifically, the pH-magnetic micro robot is observed by using a TIE inverted microscope, which is a robot with a size of 100 μm level.

[0042] The pH-responsive layer of the pH-magnetic micro-nano robot in the present application is prepared by using a pH hydrogel, can swell and shrink under pH response, so that the micro robot can respond to external pH stimulation at any time, produce bending deformation under the stress difference of the double-layer membrane hetero-material, and complete operation actions such as grabbing and releasing. Figure 6 For the optical diagram of the double-layer membrane gripper gradually merging from the initial state in the embodiment, specifically, the double-layer membrane gripper is observed under a TIE inverted microscope, NaOH solution with pH = 12 is added, and the state is observed after 5 min, and the result shows that the double-layer membrane gripper is bent.

[0043] The above only describes the preferred embodiments of the present application, and it should be noted that for ordinary skilled persons in the art, some improvements and refinements can be made without departing from the principles of the present application, and these improvements and refinements should also be considered as the protection scope of the present application.

Claims

1. A method for obtaining processing parameters of a bilayer membrane gripper in a pH-magnetic micro / nano robot. The double-layer membrane clamp includes a first clamp and a second clamp. When the first clamp and the second clamp are clamped, they form a ring-shaped structure. The double-layer membrane structure of the first clamp and the second clamp independently includes a pH-responsive layer and a non-pH-responsive layer stacked on the inner surface of the pH-responsive layer. The first clamp and the second clamp expand inward due to pH stimulation in the initial state and change to the clamping state. The processing parameters include h and m, where h = h1 + h2, m = h1 / h2, h1 is the initial thickness of the pH-responsive layer, and h2 is the initial thickness of the non-pH-responsive layer. The method includes the following steps: The design model of the double-layer membrane holder is theoretically modeled to obtain the state matrix with respect to curvature; the design model of the double-layer membrane holder corresponds to the initial state of the first clamp and the second clamp in the double-layer membrane holder; The target model of the double membrane clamp is modeled using the Timoshenko beam model to obtain the target matrix about curvature; the target model of the double membrane clamp corresponds to the clamping state in which the first clamp and the second clamp in the double membrane clamp bend inward under the effect of pH stimulation. The processing parameters are obtained based on the state matrix and the target matrix regarding curvature. The state matrix regarding curvature is represented by Equation 7: Formula 7; Where k1 is the curvature of the arc corresponding to the clamping state of the first or second clamp, R1 is the radius of curvature of the arc corresponding to the clamping state of the first or second clamp, k0 is the curvature of the arc corresponding to the initial state of the first or second clamp, θ is the central angle of the arc corresponding to the initial state of the first or second clamp, and H is the distance between the bottom end of the first or second clamp and the center of symmetry. The target matrix regarding curvature is represented by Equation 11: Formula 11; Where R0 is the radius of curvature of the arc corresponding to the initial state of the first or second clamp, λ1 is the expansion rate of the pH-responsive layer, λ2 is the expansion rate of the non-pH-responsive layer, and n is the ratio of the Young's modulus of the pH-responsive layer to the Young's modulus of the non-pH-responsive layer.

2. The method according to claim 1, characterized in that, Equation 7 is derived from Equations 1 to 6: Formula 1; Formula 2; Formula 3; Equation 4; Formula 5; Formula 6; in L is the arc length of the corresponding arc of the first or second clamp, L is the chord length of the corresponding arc of the first or second clamp in the initial state, y0 is the vertical distance between the center and the bottom of the corresponding arc of the first or second clamp in the clamping state, and y is the vertical distance between the vertex and the bottom of the corresponding arc of the first or second clamp in the clamping state. Equation 11 is obtained from Equations 8 to 10: Formula 8; Equation 9; Formula 10; Where P1 is the tensile force of the pH-responsive layer, P2 is the tensile force of the non-pH-responsive layer, M1 is the bending moment of the pH-responsive layer, M2 is the bending moment of the non-pH-responsive layer, E1 is the Young's modulus of the pH-responsive layer, E2 is the Young's modulus of the non-pH-responsive layer, I1 is the moment of inertia of the pH-responsive layer, and I2 is the moment of inertia of the non-pH-responsive layer.

3. A system for acquiring processing parameters of a bilayer membrane gripper in a pH-magnetic micro / nano robot, comprising: The theoretical modeling module is used to theoretically model the design model of the double-layer membrane holder to obtain the state matrix with respect to curvature. The design model of the double-layer membrane holder corresponds to the initial state of the first clamp and the second clamp in the double-layer membrane holder; The Temoshenko beam modeling module is used to model the target model of the double membrane clamp using the Temoshenko beam model to obtain a target matrix about curvature; the target model of the double membrane clamp corresponds to the clamping state in which the first clamp and the second clamp in the double membrane clamp bend inward under pH stimulation. The data processing and output module is used to process and output the state matrix and the target matrix about curvature to obtain the processing parameters h and m in the method of claim 1 or 2.

4. A computer-readable storage medium storing a computer program or instructions that, when executed, cause a computer to perform the method as described in claim 1 or 2.

5. A method for manufacturing a bilayer membrane gripper in a pH-magnetic micro / nano robot, comprising the following steps: A non-pH-responsive layer with an initial thickness of h2 is obtained by sequentially printing and developing photoresist. A pH-responsive layer with an initial thickness of h1 is formed on the surface of the non-pH-responsive layer by a second printing and a second development process using pH hydrogel, thus obtaining the double-layer membrane holder; h1 and h2 are calculated from the processing parameters obtained by the method described in claim 1 or 2.

6. The manufacturing method according to claim 5, characterized in that, The raw materials for preparing the pH hydrogel include N-isopropylacrylamide, acrylic acid, tetraethylmielone, and dipentaerythritol pentaacrylate.

7. The manufacturing method according to claim 5, characterized in that, The photoresist is an IP-L photoresist.

8. The manufacturing method according to any one of claims 5 to 7, characterized in that, The developing agent used in the first and second developing processes is isopropanol.

9. A pH-magnetic micro / nano robot, comprising a magnetic body and a bilayer membrane gripper, the bilayer membrane gripper comprising a first clamp and a second clamp, the bottom ends of the first clamp and the second clamp being connected to the magnetic body; the first clamp and the second clamp forming a ring-like structure when gripping, the bilayer membrane structure of the first clamp and the second clamp independently comprising a pH-responsive layer and a non-pH-responsive layer stacked on the inner surface of the pH-responsive layer; the pH-responsive layer is made of pH hydrogel; the non-pH-responsive layer is made of photoresist; the magnetic body is made of magnetic hydrogel, the magnetic hydrogel comprising NIPAM hydrogel and magnetic powder dispersed in the NIPAM hydrogel.

10. The application of the pH-magnetic micro / nano robot of claim 9 in the preparation of cell microoperating systems or drug delivery systems.

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