Light-driven hydrogel micro-nano operation robot as well as preparation method and application thereof

Abstract

The invention relates to a light-driven hydrogel micro-nano operation robot as well as a preparation method and application thereof. The light-driven hydrogel micro-nano operation robot sequentially comprises a light recognition area and a deformation execution area. The light recognition area is formed by polymerizing a first hydrogel pre-polymerization solution containing a high-concentration photo-thermal nano material; the deformation execution area is formed by blending and polymerizing a first hydrogel pre-polymerization solution containing a high-concentration photo-thermal nano material and a second hydrogel pre-polymerization solution containing a low-concentration photo-thermal nano material according to different proportions; the concentration of the photo-thermal nanometer material contained in the deformation execution area is gradually reduced from the side close to the light recognition area to the side far away from the light recognition area. The hydrogel micro-nano robot provided by the invention has the advantages of accurate light control, multi-mode motion, controllable height and batch preparation, and can realize the operations of steering, twisting, grabbing, screwing, crawling, obstacle avoidance, reconstruction and the like in a complex microenvironment.

Description

Technical Field

[0001] This invention relates to the field of micro-nano manipulation robot technology, and in particular to a light-driven hydrogel micro-nano manipulation robot, its preparation method, and its application. Background Technology

[0002] Micro- and nano-manipulation robots are intelligent systems capable of performing complex tasks such as grasping, transporting, cutting, and injecting at the micrometer or nanometer scale. They have shown great application potential in fields such as biomedicine (e.g., targeted drug delivery, single-cell manipulation, minimally invasive surgery), micro-assembly, and environmental monitoring. Soft robots composed of stimulus-responsive hydrogels are considered one of the ideal carriers for realizing these applications due to their excellent biocompatibility, flexibility, and intelligent response to external stimuli such as light, heat, and pH.

[0003] Among numerous driving methods, optical actuation is considered one of the most suitable solutions for contactless manipulation at the micro-nano scale due to its unique advantages of being wireless, remote, clean, having precisely focused energy, and being easy to spatiotemporally programmable. Near-infrared light (NIR), in particular, is highly favored due to its high penetration and low damage to biological tissues. Its typical driving mechanism is based on "light-heat-mechanical" energy conversion: photothermal nanomaterials (such as graphene and carbon nanotubes) absorb light energy to generate localized heat, which in turn triggers a reversible volume phase transition (shrinkage / swelling) in thermosensitive hydrogels (such as poly(N-isopropylacrylamide) (PNIPAm)), thereby converting light energy into mechanical motion. 4D printing technology combines smart materials with additive manufacturing technology, enabling printed structures to change their pre-defined shape, properties, or functions over time (the fourth dimension) under external stimuli, providing powerful design freedom and integrated molding capabilities for manufacturing such intelligent micro-nano robots.

[0004] However, despite its promising prospects, existing light-driven hydrogel micro / nano robot technologies and their fabrication methods still face several significant technical bottlenecks, severely restricting their performance improvement and practical applications: First, the deformation modes are limited, resulting in limited actuation performance. Existing technologies largely rely on the uniform response of materials or simple bilayer structure designs. Such designs typically only produce simple bending deformations, making it difficult to achieve complex three-dimensional movements such as twisting, crawling, and spiraling, greatly limiting the robot's adaptability in unstructured microenvironments and its ability to perform complex tasks. Furthermore, the resulting driving force and movement speed often fall short of the requirements of practical micromanipulation. Second, the manufacturing process struggles to achieve complex material distribution programming. Traditional microfabrication techniques (such as bilayer lithography) or conventional 3D printing technologies are insufficient for the high-precision and high-efficiency fabrication of structures with complex three-dimensional geometries and non-uniform material functional distributions. In particular, existing methods struggle to achieve continuous, gradual gradient distribution of photothermal nanomaterials within micro / nano structures, and this functional gradient is the intrinsic key to generating superior and more complex actuation performance. How to achieve complex three-dimensional movements in micro / nano manipulators is currently the core manufacturing bottleneck. Secondly, there are limitations in the material system and its performance. Pure hydrogel materials have weak mechanical properties and are prone to fatigue fracture during cyclic operation. Although they can be reinforced by adding nanomaterials, nanofillers are prone to aggregation, making it difficult to achieve stable and uniform dispersion in the matrix, and even more difficult to achieve a precise gradient distribution as designed. This directly affects the performance consistency, reliability, and lifespan of the device. In addition, the photothermal conversion efficiency, response speed, and cycle stability of many systems still need to be improved.

[0005] Therefore, there is an urgent need for an innovative design and manufacturing method for micro-nano manipulators to overcome the above-mentioned technical bottlenecks and develop light-driven hydrogel micro-nano manipulators with complex motion modes, strong driving force, high controllability, and mass production capability. Summary of the Invention

[0006] To address one or more technical problems of existing light-driven hydrogel micro / nano robots, such as limited deformation modes, manufacturing process constraints, poor material properties, and insufficient intelligent control, this invention provides a light-driven hydrogel micro / nano manipulator robot, its fabrication method, and operating system. This invention provides a hydrogel micro / nano robot that can be precisely light-controlled, exhibits multimodal motion, is highly controllable, and can be mass-produced. It can perform complex movements such as turning, twisting, grasping, spiraling (spiraling forward), crawling, and obstacle avoidance, as well as multimodal and reconfigurable micromanipulations in complex and tortuous microenvironments (such as human vascular networks and interstitial spaces).

[0007] The present invention provides, in a first aspect, a light-driven hydrogel micro / nano manipulator robot, comprising a micro / nano manipulator body, the micro / nano manipulator body comprising, sequentially, a light recognition region and a deformation execution region; the light recognition region is formed by polymerization of a first hydrogel prepolymer containing a high concentration of photothermal nanomaterials under the action of a photoinitiator; the deformation execution region is formed by blending the first hydrogel prepolymer containing a high concentration of photothermal nanomaterials and a second hydrogel prepolymer containing a low concentration of photothermal nanomaterials in different proportions and then polymerizing them under the action of a photoinitiator, such that the concentration of photothermal nanomaterials in the deformation execution region gradually decreases from the side closer to the light recognition region to the side farther away from the light recognition region.

[0008] Preferably, the first hydrogel prepolymer contains N-isopropylacrylamide, N-tert-butylacrylamide, N,N'-methylenebisacrylamide, a photoinitiator, nanoclay, photothermal nanomaterials, and water. The concentration of photothermal nanomaterials in the first hydrogel prepolymer is 1.0 mg / mL to 1.5 mg / mL, the mass percentage of nanoclay in the first hydrogel prepolymer is 4 wt% to 6 wt%, and / or the molar ratio of N-isopropylacrylamide to N-tert-butylacrylamide in the first hydrogel prepolymer is (5~1). 0):1; and / or the second hydrogel prepolymer contains N-isopropylacrylamide, acrylamide, N,N'-methylenebisacrylamide, a photoinitiator, sodium alginate, photothermal nanomaterials and water, wherein the concentration of photothermal nanomaterials in the second hydrogel prepolymer is 0.05 mg / mL to 0.1 mg / mL, the mass percentage of sodium alginate in the second hydrogel prepolymer is 1 wt% to 2 wt%, and / or the molar ratio of N-isopropylacrylamide to acrylamide in the second hydrogel prepolymer is (8~12):1.

[0009] Preferably, the photothermal nanomaterial is a composite of reduced graphene oxide and carbon nanotubes. More preferably, the mass ratio of reduced graphene oxide to carbon nanotubes is (0.5~2):1. And / or when forming the deformation execution region, the first hydrogel prepolymer and the second hydrogel prepolymer are blended in different proportions by microfluidic co-extrusion. More preferably, the proportion of the first hydrogel prepolymer and the second hydrogel prepolymer changes continuously from 100:0 to 0:100 along the microfluidic co-extrusion direction.

[0010] Preferably, the micro-nano manipulation robot body has a biomimetic structure, preferably a micro-clamping structure, a micro-hand structure, a micro-basket structure, or a crab-like structure.

[0011] Preferably, the volume phase transition temperature of the photorecognition region is 35~40℃; the volume phase transition temperature of the deformation execution region is lower than that of the photorecognition region, and the volume phase transition temperature range of the deformation execution region is greater than that of the photorecognition region; and / or the deformation execution region is loaded with pH-responsive hydrogel and / or drug molecules.

[0012] In a second aspect, the present invention provides a method for fabricating the light-driven hydrogel micro / nano manipulator described in the first aspect, the method comprising the following steps: (1) Prepare the first hydrogel prepolymer as ink A, and prepare the second hydrogel prepolymer as ink B; (2) Design a printing model of a light-driven hydrogel micro-nano manipulation robot, which includes a light recognition area and a deformation execution area in sequence. Use ink A and ink B as printing materials for 4D printing. The printing head used in the 4D printing is a multi-channel microfluidic co-extrusion printing head. During the 4D printing process, the ratio of ink A and ink B in the multi-channel microfluidic co-extrusion printing head is adjusted to carry out the 4D printing of the light-driven hydrogel micro-nano manipulation robot, and the light-driven hydrogel micro-nano manipulation robot is obtained.

[0013] Preferably, the multi-channel microfluidic co-extrusion printhead includes an ink A channel, an ink B channel, a manifold, and a nozzle; one end of the manifold is connected to the ink A channel, the other end is connected to the ink B channel, and the middle part of the manifold is connected to the nozzle; the multi-channel microfluidic co-extrusion printhead further includes a microfluidic valve for controlling the ratio of ink A and ink B; preferably, the multi-channel microfluidic co-extrusion printhead further includes piezoelectric valves disposed at the outlets of the ink A channel and the ink B channel, the piezoelectric valves being controlled by a variable voltage electric device to adjust the ratio of ink A and ink B; preferably, the diameter of the nozzle is 50-200 μm; preferably, the temperature of the printing platform is 4-10℃ during 4D printing; preferably, an ultraviolet LED light source is used to irradiate the printing platform during 4D printing; preferably, the ultraviolet LED light source emits ultraviolet light with a wavelength of 365-405 nm.

[0014] In a third aspect, the present invention provides a multi-channel microfluidic co-extrusion printhead for implementing the preparation method described in the second aspect of the present invention. The multi-channel microfluidic co-extrusion printhead includes an ink A channel, an ink B channel, a manifold, and a nozzle. One end of the manifold is connected to the ink A channel, and the other end is connected to the ink B channel. The middle portion of the manifold is connected to the nozzle. The multi-channel microfluidic co-extrusion printhead further includes a microfluidic valve for controlling the ratio of ink A to ink B. Preferably, the multi-channel microfluidic co-extrusion printhead also includes piezoelectric valves disposed at the outlets of the ink A channel and the ink B channel. The piezoelectric valves are controlled by a variable voltage electric device to adjust the ratio of ink A to ink B.

[0015] In a fourth aspect, the present invention provides an operating system for manipulating the light-driven hydrogel micro / nano manipulator described in the first aspect or the light-driven hydrogel micro / nano manipulator prepared by the preparation method described in the second aspect. The operating system includes a near-infrared laser source, a light field modulation device, and a control unit. The near-infrared laser source is used to provide near-infrared laser light to the light-driven hydrogel micro / nano manipulator. The light field modulation device is used to modulate the near-infrared laser light into a dynamically programmable light pattern and irradiate the light-driven hydrogel micro / nano manipulator. The control unit is used to control the scanning path, irradiation time, and light intensity of the dynamically programmable light pattern to trigger and control the movement of the light-driven hydrogel micro / nano manipulator.

[0016] The present invention provides, in a fifth aspect, the application of the light-driven hydrogel micro / nano manipulator robot described in the first aspect or the light-driven hydrogel micro / nano manipulator robot prepared by the preparation method described in the second aspect of the present invention in the fields of biomedical micromanipulation or microassembly.

[0017] Compared with the prior art, this invention provides a light-driven hydrogel micro / nano manipulator robot based on microfluidic co-extrusion gradient 4D printing and its preparation method, which has at least the following significant technical effects: (1) The light-driven hydrogel micro-nano manipulator in this invention can achieve complex multi-dimensional motion patterns: due to the continuous and gradual photothermal nanomaterial concentration gradient constructed inside the robot, it can generate a huge and precise internal stress gradient under near-infrared light irradiation. This allows a single, uniform light stimulus to excite complex three-dimensional deformations far exceeding simple bending, such as twisting, spiraling, rolling, crawling, etc., which greatly enhances the robot's agility, adaptability and task execution capability in complex and narrow micro-environments (such as biological tissue gaps and microchannels), and solves the technical bottleneck of the traditional uniform or double-layer structure driving mode being single and only able to achieve simple deformation.

[0018] (2) The present invention improves the driving performance and response efficiency of the light-driven hydrogel micro-nano manipulation robot: the three-dimensional thermally conductive network formed by photothermal nanomaterials (such as rGO / CNTs composite) combined with gradient distribution realizes efficient absorption of light energy and rapid heat conduction; the light-driven hydrogel micro-nano manipulation robot of the present invention has high photothermal conversion efficiency, fast response speed (up to the second level or even the millisecond level), stronger driving force, and good deformation reversibility, and can withstand repeated cyclic driving without performance degradation.

[0019] (3) The preparation method of the present invention can achieve precise control of structure and performance at the micro-nano scale. By using microfluidic co-extrusion gradient 4D printing technology, complex three-dimensional micro-nano structures with preset deformation and functional response characteristics can be obtained in one molding process by continuously adjusting the material ratio and spatial distribution during the printing process. This method overcomes the technical bottleneck of traditional manufacturing processes that make it difficult to achieve precise and coordinated control of material composition and structure at the micro-scale, and the prepared structures have high repeatability and good uniformity.

[0020] (4) This invention introduces laponite as a physical crosslinking point and reinforcing phase, and works synergistically with the rGO / CNTs composite system to significantly improve the toughness, fatigue resistance, and mechanical strength of the hydrogel network. This results in the light-driven hydrogel micro / nano manipulation robot having higher structural stability and repeatability when performing micromanipulations. The material system in this invention makes the light-driven hydrogel micro / nano manipulation robot less prone to damage during operation, and it can stably output micro-Newton to nano-Newton level operating forces without cracking or performance degradation, significantly extending its service life and improving its operational reliability.

[0021] (5) Functional logic of the light-driven hydrogel micro / nano manipulation robot in this invention: The single "light-heat-deformation" response is broken down into a cascaded process of "sensing-triggering-execution", which is more similar to the working principle of a living organism, and the level of intelligence is significantly improved. The sharpening of the action of the light-driven hydrogel micro / nano manipulation robot in this invention: The abrupt phase transition in the light recognition area, that is, the rapid volume change of the light response area under light, forms instantaneous stress release or driving force output, making the grasping action faster and more decisive, the grasping action response speed is significantly accelerated, and the action process is more clear and stable, avoiding the shortcomings of slow response and insufficient output force of traditional uniform hydrogels. The performance optimization of the light-driven hydrogel micro / nano manipulation robot in this invention: The light recognition area is responsible for providing power, and the deformation execution area is responsible for achieving large deformation. Each performs its own function, and the overall performance is superior to that of a material system with uniform function. The enhanced controllability of the light-driven hydrogel micro / nano manipulation robot in this invention: By controlling the light intensity, it is possible to precisely control whether the trigger threshold is reached, thereby realizing digital control of the grasping action (i.e.: turning the light on / off = grasping / releasing).

[0022] (6) Material gradient design of the light-driven hydrogel micro / nano manipulator in this invention: By setting a functional component (photothermal nanomaterial) gradient along the robot's main axis, i.e., from the light-sensing end to the manipulating end, the concentration of the photothermal nanomaterial gradually decreases, which can produce torsional deformation (similar to a propeller) under light. By controlling the position of the light, the direction and force of the torsion can be changed in real time, thereby achieving autonomous steering and helical propulsion. This motion mode is extremely efficient in viscous fluids (such as blood) and is the only effective way to traverse complex microenvironments. The continuous functional gradient is equivalent to providing an infinite number of "double layers". Its deformation is continuous and gradual, similar to our muscle movements, and can smoothly transition from one posture to another. This gentle movement is crucial for non-destructive biological manipulation and cannot be achieved with homogeneous materials.

[0023] (7) The light-driven hydrogel micro / nano manipulation robot of this invention possesses excellent biocompatibility and application potential: the robot uses hydrogel as a matrix, which is soft and has a low modulus, and will not cause damage when manipulating fragile targets such as cells. Near-infrared light has good penetrability and is harmless to biological tissues. This makes this invention show great application prospects in biomedical fields such as targeted drug delivery, minimally invasive surgery, and intracellular manipulation, and it can also be used in non-biological fields such as micro-assembly and environmental monitoring. Attached Figure Description

[0024] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention and are only for more clearly illustrating the technical solutions of the embodiments of the present invention, and therefore should not be regarded as a limitation of the scope. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort. The drawings of the present invention are provided for illustrative purposes only, and the proportions, sizes, and quantities of the parts in the drawings may not be consistent with the actual product.

[0025] Figure 1 This is a schematic diagram of the structure of the multi-channel microfluidic co-extrusion printhead used in some specific embodiments of the present invention; Figure 1 In the diagram, 1: Ink A channel; 11: Ink A inlet; 2: Ink B channel; 21: Ink B inlet; 3: Manifold; 4: Nozzle; 5: Piezoelectric valve; 6: Variable voltage device; 7: Printing platform; Figure 2 These are schematic diagrams of the appearance of the light-driven hydrogel micro / nano manipulation robot in some specific embodiments of the present invention; Figure 3 This is a schematic diagram of a light-driven hydrogel micro / nano manipulator robot moving within human blood vessels in some specific embodiments of the present invention. Figure 4 These are schematic diagrams illustrating the motion changes of a light-driven hydrogel micro / nano manipulator robot in some specific embodiments of the present invention. Figure 4 The illustration shows the motion patterns of a light-driven hydrogel micro / nano manipulator robot before and after deformation, from static to activated. It demonstrates that a single uniform light stimulus is transformed into asymmetric contractile strain in space through internal gradient design, thereby outputting multi-degree-of-freedom motion. Detailed Implementation

[0026] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below in conjunction with the embodiments of this invention. Obviously, the described embodiments are only some, not all, of the embodiments of this invention. 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.

[0027] In a first aspect, this invention provides a light-driven hydrogel micro / nano manipulator robot, comprising a micro / nano manipulator robot body, the micro / nano manipulator robot body sequentially including a light recognition region and a deformation execution region, such as... Figure 2 As shown; the photorecognition region is formed by polymerization of a first hydrogel prepolymer containing a high concentration of photothermal nanomaterials under the action of a photoinitiator; the deformation execution region is formed by blending a first hydrogel prepolymer containing a high concentration of photothermal nanomaterials and a second hydrogel prepolymer containing a low concentration of photothermal nanomaterials in different proportions and then polymerizing them under the action of a photoinitiator, so that the concentration of photothermal nanomaterials in the deformation execution region gradually decreases from the side closer to the photorecognition region to the side farther away from the photorecognition region; in this invention, polymerization under the action of a photoinitiator is also the chemical process by which the hydrogel prepolymer is cured by ultraviolet light to form a three-dimensional network structure.

[0028] The light-driven hydrogel micro / nano manipulator described in this invention is preferably fabricated using microfluidic co-extrusion gradient 4D printing technology. It is a light-driven hydrogel micro / nano manipulator with a continuous functional gradient distribution. The light-driven hydrogel micro / nano manipulator of this invention integrates photothermal nanomaterials in a concentration gradient distribution in a temperature-sensitive hydrogel matrix, thereby generating asymmetric internal stress under near-infrared light irradiation, realizing complex three-dimensional deformation and movement. This gradient design achieves multi-degree-of-freedom and multi-modal deformation through internal stress gradient, greatly expanding the robot's motion capability. The structural feature of the light-driven hydrogel micro / nano manipulator described in this invention lies in its internal functionally differentiated material system and gradient distribution of photothermal nanomaterials, enabling intelligent cascade responses of light recognition, triggering, and execution. The robot body is composed of a stimulus-responsive hydrogel matrix, and its internal structure possesses a pre-designed functional gradient distribution of photothermal nanomaterials, achieved, for example, through microfluidic co-extrusion gradient 4D printing technology. This gradient distribution includes a light recognition region with high concentrations of photothermal nanomaterials and a deformation execution region with low concentrations of photothermal nanomaterials. The light recognition region undergoes a rapid phase transition upon reaching a specific photothermal trigger threshold, thereby driving the deformation execution region to generate preset, complex, non-uniform contraction strain, achieving complex three-dimensional movements including twisting, grasping, spiraling, crawling, and conveying. In this invention, the operational ends of the light recognition region and the deformation execution region form a continuous functional gradient, ensuring effective transmission of mechanical stress and endowing the structure with richer deformation capabilities.

[0029] According to some preferred embodiments, the first hydrogel prepolymer contains N-isopropylacrylamide (NIPAm), N-tert-butylacrylamide (TBAm), a crosslinking agent N,N'-methylenebisacrylamide (MBAA), a photoinitiator, nanoclay, photothermal nanomaterials, and water. The concentration of photothermal nanomaterials in the first hydrogel prepolymer is 1.0 mg / mL to 1.5 mg / mL (e.g., 1.0, 1.1, 1.2, 1.3, 1.4, or 1.5 mg / mL), and the mass percentage of nanoclay in the first hydrogel prepolymer is 4 wt% to 6 wt% (e.g., 4, 4.5, 5, 5.5, or 6 wt%). And / or in the first hydrogel prepolymer, the N-isopropylacrylamide and N-tert-butylacrylamide... The molar ratio of butylacrylamide is (5~10):1 (e.g., 5:1, 6:1, 7:1, 8:1, 9:1 or 10:1); In this invention, the addition of the nanoclay serves as a physical crosslinking point and reinforcing phase to sharpen the phase transition process and improve mechanical properties, thereby constructing a composite smart material with excellent photothermal responsiveness, superior mechanical properties and good biocompatibility for the light-driven hydrogel micro / nano manipulator; In this invention, the first hydrogel prepolymer is polymerized under the action of a photoinitiator to form a first hydrogel composite material, the first hydrogel composite material constitutes the photorecognition region, and the first hydrogel composite material contains a first thermosensitive polymer matrix and photothermal nanomaterials and nanoclay composited in the first thermosensitive polymer matrix.

[0030] In this invention, the mass percentage of nano-clay in the first hydrogel prepolymer is 4wt%~6wt%. This concentration range allows for the formation of appropriate physical cross-linking points and reinforcing phases in the hydrogel network, which not only sharpens the phase transition process of the hydrogel, making the light-driven response faster and the action more decisive, but also significantly improves the toughness, fatigue resistance, and mechanical strength of the hydrogel, thereby ensuring that the micro-nano manipulation robot is not easily damaged during operation. If the nano-clay content is lower than this range, there are insufficient physical cross-linking points, and the hydrogel network structure is relatively loose, resulting in a relatively slow phase transition process and less sharp action, while mechanical strength and fatigue resistance will also decrease. If the nano-clay content is higher than this range, the hydrogel network is relatively dense, which may reduce the phase transition capability of the hydrogel and increase the energy required for light-driven operation, affecting the response efficiency and reliability of the micro-nano manipulation robot.

[0031] According to some preferred embodiments, the second hydrogel prepolymer contains N-isopropylacrylamide (NIPAm), acrylamide (AAm), N,N'-methylenebisacrylamide (MBAA), a photoinitiator, sodium alginate, photothermal nanomaterials, and water. The concentration of the photothermal nanomaterials in the second hydrogel prepolymer is 0.05 mg / mL to 0.1 mg / mL (e.g., 0.05, 0.06, 0.07, 0.08, 0.09, or 0.1 mg / mL). The mass percentage of sodium alginate in the second hydrogel prepolymer is 1 wt% to 2 wt% (e.g., 1, 1.5, or 2 wt%). And / or in the second hydrogel prepolymer, the N- The molar ratio of isopropylacrylamide to acrylamide is (8~12):1 (e.g., 8:1, 9:1, 10:1, 11:1 or 12:1); in this invention, the addition of sodium alginate serves as a toughening agent to improve the elongation at break and flexibility of the network; the first hydrogel prepolymer and the second hydrogel prepolymer are blended in different proportions and polymerized under the action of a photoinitiator to form a second hydrogel composite material, the deformation execution area is composed of the second hydrogel composite material, the second hydrogel composite material includes a second thermosensitive polymer matrix and photothermal nanomaterials composited in the second thermosensitive polymer matrix, as well as nanoclay and / or sodium alginate composited in the second thermosensitive polymer matrix.

[0032] In this invention, preferably, the sodium alginate content in the second hydrogel prepolymer is 1wt%~2wt%. This concentration range can significantly improve the elongation at break and flexibility of the hydrogel composite material in the hydrogel network, enabling the deformation execution area to bend and twist under light drive without easily breaking, ensuring smooth and continuous movement of the micro-nano manipulation robot. If the sodium alginate content is lower than this range, the network toughness and elongation at break are low, and the hydrogel is prone to local breakage or insufficient deformation during operation. If the sodium alginate content is higher than this range, the hydrogel network is too dense or the viscosity is too high, which may affect the material's flowability and co-extrusion printing accuracy. In addition, it will also increase or decrease the response efficiency and reliability of the micro-nano manipulation robot.

[0033] This invention does not impose specific limitations on the type, amount, and crosslinking agent of the photoinitiator. Those skilled in the art can make conventional choices. In some specific embodiments, the photoinitiator used in the first hydrogel prepolymer and the second hydrogel prepolymer can be, for example, 2-hydroxy-2-methyl-1-phenyl-1-propanone and / or 1-(4-isopropylphenyl)-2-hydroxy-2-methyl-1-propanone. The amount of the photoinitiator is, for example, 0.05 to 1 wt% of the mass of N-isopropylacrylamide, and the amount of the crosslinking agent is, for example, 0.5 to 1.5 wt% of the mass of N-isopropylacrylamide.

[0034] According to some preferred embodiments, the photothermal nanomaterial is a composite of reduced graphene oxide (rGO) and carbon nanotubes (CNTs) (also referred to as an rGO / CNTs photothermal nanomaterial composite). Preferably, the composite of reduced graphene oxide and carbon nanotubes is formed by mixing the reduced graphene oxide and carbon nanotubes at a mass ratio of (0.5~2):1 (e.g., 0.5:1, 1:1, 1.5:1 or 2:1). In this invention, it is preferred to use the composite of reduced graphene oxide and carbon nanotubes as the photothermal nanomaterial, which has excellent photothermal effect and low cost. And / or when forming the deformation execution region, the first hydrogel prepolymer and the second hydrogel prepolymer are blended in different proportions (e.g., continuous blending) by microfluidic co-extrusion, preferably microfluidic co-extrusion gradient 4D printing. Preferably, the proportion (volume feed ratio) of the first hydrogel prepolymer and the second hydrogel prepolymer is along the microfluidic co-extrusion. The ratio of the first hydrogel prepolymer to the second hydrogel prepolymer changes continuously (gradually) from 100:0 to 0:100 in this invention, for example, along the microfluidic co-extrusion gradient 4D printing direction, to obtain a spatial gradient distribution in which the concentration of photothermal nanomaterials gradually decreases along the printing direction. That is, during the microfluidic co-extrusion process, the ratio (volume feed ratio) of the first hydrogel prepolymer to the second hydrogel prepolymer gradually changes along the co-extrusion direction, so that the volume percentage (volume content) of the first hydrogel prepolymer gradually decreases from 100% to 0% from the side closer to the photorecognition area to the side farther from the photorecognition area, while the volume percentage (volume content) of the second hydrogel prepolymer gradually increases from 0% to 100% from the side closer to the photorecognition area to the side farther from the photorecognition area, thereby forming a continuously decreasing distribution of photothermal nanomaterial concentration in the deformation execution area.

[0035] According to some preferred embodiments, the micro-nano manipulator body is a biomimetic structure, preferably a micro-pincer structure, a micro-hand structure, a micro-basket structure, or a crab-like structure (e.g., ...). Figure 2 (as shown); In this invention, the light recognition area is located, for example, at the end and / or engagement portion of the bionic structure, and the deformation execution area is located, for example, at the joint and / or body of the bionic structure.

[0036] The present invention does not impose a specific limitation on the size of the light-driven hydrogel micro-nano manipulator robot. Those skilled in the art can make conventional choices, for example, the outer contour size of the light-driven hydrogel micro-nano manipulator robot can be between 1 micrometer and 1000 micrometers.

[0037] According to some preferred embodiments, the volume phase transition temperature of the optical recognition region is 35~40℃, which can quickly reach and exceed this threshold under near-infrared light irradiation, producing abrupt contraction and playing a mechanical triggering role; the volume phase transition temperature of the deformation execution region is lower than that of the optical recognition region, and the volume phase transition temperature range of the deformation execution region is larger than that of the optical recognition region, and the deformation execution region maintains high flexibility and large deformation capability at the triggering temperature; in this invention, the volume phase transition temperature of the deformation execution region is, for example, 25℃~34℃, and the deformation execution region... The volumetric phase transition temperature range of the row region is wider than that of the photosensitive region. This design allows the deformation execution region to exhibit a gradual and continuous volumetric response when heated. When the photosensitive region undergoes abrupt contraction and a mechanical triggering force is applied, smooth and controllable bending or torsional deformation can be generated through stress transmission. Simultaneously, the lower and wider volumetric phase transition temperature range helps reduce the instantaneous requirements on the light-driven intensity, improving the smoothness and repeatability of the action. If the volumetric phase transition temperature is too high, the deformation execution region will struggle to produce the desired auxiliary response after being triggered by the photosensitive region, reducing propulsion / grabbing efficiency and increasing drive energy requirements. In this invention, the volumetric phase transition temperatures of the hydrogel in the photosensitive region and the deformation execution region are mainly controlled by adjusting the monomer molar ratio and the crosslinking agent content.

[0038] In this invention, different functional regions of the light-driven hydrogel micro / nano manipulator may also integrate other functional components.

[0039] According to some preferred embodiments, the deformable execution region is preferably loaded with pH-responsive hydrogel and / or drug molecules at the operating end of the deformable execution region, which can realize the integrated function of driving and treatment.

[0040] In a second aspect, the present invention provides a method for fabricating the light-driven hydrogel micro / nano manipulator described in the first aspect, the method comprising the following steps: (1) Prepare a first hydrogel prepolymer as ink A and a second hydrogel prepolymer as ink B; when preparing the first hydrogel prepolymer and the second hydrogel prepolymer, for example, perform ultrasonic dispersion and centrifugal degassing treatment by centrifugal degassing machine to obtain a uniform and printable ink system. (2) A printing model of a light-driven hydrogel micro-nano manipulation robot is designed, which includes a light recognition area and a deformation execution area. Ink A and ink B are used as printing materials for 4D printing. The printing head used in the 4D printing is a multi-channel microfluidic co-extrusion printing head. During the 4D printing process, the 4D printing of the light-driven hydrogel micro-nano manipulation robot (i.e., microfluidic co-extrusion gradient 4D printing) is carried out by adjusting the ratio of ink A and ink B in the multi-channel microfluidic co-extrusion printing head. The light-driven hydrogel micro-nano manipulation robot is obtained. In this invention, microfluidic co-extrusion gradient 4D printing can also be abbreviated as gradient 4D printing. It should be noted that the "microfluidic" in this invention does not only refer to the flow process of fluid in a micro-channel, but also refers to the real-time adjustment of the flow rate and mixing ratio of various inks during the printing process by setting the feed channel and piezoelectric valve and other precision control elements inside the printing head. Through this microfluidic technology, the ratio of different inks can be dynamically changed in the continuous printing path, thereby constructing a functional area with a continuous concentration gradient distribution inside the molded structure and realizing the precise manufacturing of the gradient structure.

[0041] The light-driven hydrogel micro / nano manipulator described in this invention solves the problem of limited deformation modes: traditional hydrogel robots can only perform simple bending, while the gradient design in this invention enables complex three-dimensional movements (such as twisting, grasping, spiraling, crawling, etc.). The microfluidic co-extrusion gradient 4D printing method employed in this invention achieves integrated molding of the robot, solving the challenges of manufacturing precision and functional integration. The microfluidic co-extrusion gradient 4D printing technology controls the ratio of the two ink streams, forming a lateral material concentration gradient in situ within the micro-nozzle during printing, and then curing it in situ with ultraviolet light. This achieves precise control of composition and structure at the micro / nano scale, essentially transforming complex... The "deformation program" is precisely and digitally encoded into the micro-nano scale structure of the light-driven hydrogel micro-nano manipulator, overcoming the limitation that traditional photolithography or 3D printing cannot achieve a continuous gradient distribution; it improves driving performance and response speed. The concentration gradient distribution of photothermal nanomaterials optimizes the heat conduction path, thereby improving photothermal conversion efficiency and response speed. In this invention, the concentration gradient distribution of the photothermal nanomaterials can be linearly or non-linearly continuous in a specific dimension of the robot structure (such as the height direction and / or the length direction). In some specific embodiments, linear continuous variation is preferred.

[0042] In this invention, the fabricated light-driven hydrogel micro / nano manipulator exhibits excellent environmental adaptability. Its material system is highly sensitive to environmental parameters such as temperature (T), pH, ionic strength (I), and enzyme concentration. Environmental signals can directly regulate the physicochemical states of the hydrogel network, including its swelling degree, phase transition temperature (LCST), and mechanical modulus, thereby establishing a fundamental bias in the overall driving state and automatically adjusting its motion mode and manipulation force. By introducing a continuous compositional gradient design into the material, minute and uniform differences in physical properties caused by environmental changes are amplified into non-uniform response regions distributed along the structure, thus forming a spatially distinguishable stress or deformation sensitivity field within the structure. When irradiated with near-infrared light, the photothermal effect in this gradient system couples linearly or non-linearly with the environmental modulation signal, and the driving system reaches a new thermo-chemical-mechanical dynamic equilibrium under the combined action of the photothermal field and the environmental field. The gradient interface avoids abrupt changes in material properties, ensuring the continuous transmission of stress and deformation within the structure. This allows the robot to output smooth, controllable, and environmentally adaptable continuous movements (smooth and continuous motion) under different environmental conditions. This makes the robot's movements gentle and continuous, and safer for fragile biological tissues (such as cells). In the micro-nano world where wiring is impossible, gradient design allows a single, uniform light stimulus to pass through the gradient interface within the material, generating complex movements such as twisting, crawling, and grasping—that is, a single stimulus can produce complex responses. This mechanism significantly improves the robot's operational stability and response accuracy in complex physiological or microfluidic environments.

[0043] According to some preferred embodiments, for example, Figure 1As shown, the multi-channel microfluidic co-extrusion printhead includes an ink A channel 1, an ink B channel 2, a manifold 3, and a nozzle 4. Ink A channel 1 and ink B channel 2 are two independent feed channels, with a stable feed back pressure provided by a constant pressure injection pump or a constant flow injection pump. Ink A enters ink A channel 1 from ink A inlet 11, and ink B enters ink B channel 1 from ink B inlet 21. In this invention, the injection pump can be, for example, a Harvard Apparatus PHD pump. Ultra; In this invention, when the feed channel of the multi-channel microfluidic co-extrusion printhead is composed of ink A channel and ink B, the multi-channel microfluidic co-extrusion printhead is also referred to as a dual-channel microfluidic co-extrusion printhead; one end of the manifold 3 is connected to the ink A channel 1, the other end is connected to the ink B channel 2, and the middle part of the manifold 3 is connected to the nozzle 4; In this invention, by connecting both ends of the manifold to the ink A channel and the ink B channel respectively, and connecting the middle part of the manifold to the nozzle, the two fluids are stably merged before entering the nozzle. This structure forms a controlled manifold area, allowing ink A and ink B to flow in parallel in a laminar state within the manifold, avoiding interface disturbances caused by turbulent mixing. Utilizing the laminar effect, a continuous concentration gradient distribution (without turbulent mixing) is formed laterally in the manifold, maintaining a clear interface between different components. As the feed ratio of each channel is adjusted... The multi-channel microfluidic co-extrusion printhead allows for dynamic control of the gradient distribution, enabling a smooth transition and continuous change in material composition during printing. This results in a light-driven hydrogel micro / nano manipulation robot with uniform structure and performance and a stable interface. The multi-channel microfluidic co-extrusion printhead also includes a microfluidic valve for controlling the ratio of ink A and ink B. Preferably, the multi-channel microfluidic co-extrusion printhead further includes a piezoelectric valve 5 located at the outlet (end of the feed channel) of ink A channel 1 and ink B channel 3. The piezoelectric valve 5 is controlled by a variable voltage device 6 to adjust the ratio of ink A to ink B. The nozzle 4 ejects (jets) printing material from the printing platform 7 for 4D printing. The piezoelectric valve in this invention is a piezoelectric microvalve (also referred to as a piezoelectric actuated microvalve). This invention does not specifically limit the piezoelectric actuated microvalve; those skilled in the art can choose conventionally, for example, using a valve such as Lee's. The company's product line features micro-valve based on the piezoelectric drive principle. Specifically, each feed channel has a micro-active switch integrated at its end, which is a piezoelectric actuated micro-valve. An independently adjustable voltage signal is applied to the piezoelectric actuated micro-valve via a variable voltage device, precisely controlling the displacement of the valve core of the piezoelectric actuated micro-valve. This allows for real-time and independent adjustment of the opening size of each feed channel outlet. By controlling the opening size, the instantaneous volume feed ratio (mixing ratio) of ink A and ink B can be directly and quickly adjusted. The two ink streams form a transverse, continuously transitioning concentration gradient in the confluence cavity of the printhead based on the laminar flow effect.The variable voltage device, for example, is a voltage controller. Its output voltage amplitude and rate of change can be set according to the printing path and material distribution requirements, enabling continuous adjustment of the material ratio in different areas. In this way, a smooth material composition gradient can be formed during printing, ensuring that the performance distribution of the resulting structure remains consistent with design requirements, guaranteeing printing accuracy and repeatability. In this invention, the voltage controller can be, for example, an Arduino. This voltage controller receives digital instructions from a host controller and outputs a precisely adjustable analog voltage signal (e.g., 0~10V) to drive a piezoelectric actuator, thereby precisely adjusting the micron-level displacement of the piezoelectric actuator microvalve core. This achieves continuous and dynamic control of the flow ratio of ink A and ink B. That is, applying a voltage signal, for example, 0~10V, can precisely adjust the valve core displacement of the piezoelectric valve, controlling the opening size (with micron-level accuracy). This invention does not impose specific limitations on the host controller; those skilled in the art can choose conventionally.

[0044] The multi-channel microfluidic co-extrusion printhead structure used in this invention features a piezoelectric adjustable feeding system, enabling high-precision dynamic control of the ratio of ink A to ink B. The printhead includes an independent multi-channel feeding structure, a manifold, and a piezoelectric valve located at the outlet of the feeding channel. Driven by a variable voltage device, the piezoelectric valve deforms, allowing for rapid and precise dynamic adjustment of the flow rates of the two channels, thus achieving real-time ratio control of ink A and ink B. This design also creates a stable laminar mixing state within the manifold, maintaining a clearly defined mixing interface between different inks. This interface position continuously moves with changes in the channel volume feeding ratio, enabling controllable spatial distribution of material components during printing. This printhead possesses advantages such as piezoelectric precision actuation, dynamic flow control, multi-channel laminar transport, and continuous interface adjustment, ensuring a smooth transition in component ratio conversion during printing (e.g., 100:0 → 50:50 → 0:100), avoiding structural inhomogeneity and performance fluctuations caused by abrupt mixing.

[0045] According to some preferred embodiments, the nozzle (also referred to as a micro-nozzle) has a diameter of 50-200 μm, which ensures the micro-nano scale of the extruded filament.

[0046] According to some preferred embodiments, the temperature of the printing platform 7 is 4~10°C during 4D printing; in this invention, it is preferred that the temperature of the printing platform is 4~10°C, which can slow down the reaction speed and ensure printing accuracy.

[0047] According to some preferred embodiments, when performing 4D printing, an ultraviolet LED light source is used to irradiate the printing platform; preferably, the ultraviolet LED light source used emits ultraviolet light with a wavelength of 365~405nm; in this invention, a composite ink with a concentration gradient distribution is extruded from a micro-nozzle (50-200μm in diameter) and printed layer by layer on a low-temperature printing platform (4~10℃) according to a preset three-dimensional model (printing model); while printing and extruding, an ultraviolet LED light source (e.g., 365nm) is used to synchronously scan and irradiate the extruded gradient hydrogel filaments to achieve in-situ curing, thereby accurately fixing the complex gradient distribution structure.

[0048] This invention utilizes microfluidic co-extrusion gradient 4D printing to print photothermal nanomaterials according to a concentration gradient from high to low. These nanomaterials interweave at the microscale, forming a light-driven micro / nano manipulator with a continuously varying gradient interface in composition, structure, and properties. During the printing process, aside from synchronously applying ultraviolet light to the printing path and controlling the printing platform temperature, parameters such as printing speed, jetting pressure, layer thickness, and printing spacing are not specifically limited and can be conventionally selected by those skilled in the art. The implementation of this invention is not limited by specific printing parameters. In some specific embodiments, the printing speed can be, for example, 2~4 mm / s, the jetting pressure can be, for example, 30~50 kPa, the layer thickness can be, for example, 70~90 μm, and the printing spacing can be, for example, 80~100 μm. In some more specific embodiments, the printing speed can be, for example, 3 mm / s, the jetting pressure can be, for example, 40 kPa, the layer thickness can be, for example, 80 μm, and the printing spacing can be, for example, 90 μm.

[0049] According to some preferred embodiments, in step (2), after using ink A and ink B as printing materials for 4D printing, the step of post-processing the 4D printed gel structure is also included; specifically, for example, the printed gel structure is removed from the platform and soaked in deionized water for more than 24 hours to remove unreacted monomers and reach a swelling equilibrium state, and finally obtains a light-driven hydrogel micro-nano manipulation robot.

[0050] In a third aspect, the present invention provides a multi-channel microfluidic co-extrusion printhead, which is used to implement the preparation method described in the second aspect of the present invention, for example, as... Figure 1As shown, the multi-channel microfluidic co-extrusion printhead includes an ink A channel 1, an ink B channel 2, a manifold 3, and a nozzle 4. Ink A enters the ink A channel 1 from the ink A inlet 11, and ink B enters the ink B channel 2 from the ink B inlet 21. One end of the manifold 3 is connected to the ink A channel 1, and the other end is connected to the ink B channel 2. The middle part of the manifold 3 is connected to the nozzle 4. The multi-channel microfluidic co-extrusion printhead also includes a microfluidic valve for controlling the ratio of ink A and ink B. Preferably, the multi-channel microfluidic co-extrusion printhead also includes a piezoelectric valve 5 disposed at the outlet of the ink A channel 1 and the ink B channel 2. The piezoelectric valve 5 is controlled by a variable voltage device 6 to adjust the ratio of ink A and ink B. The nozzle 4 ejects printing material directly onto the printing platform 7 for 4D printing.

[0051] In a fourth aspect, this invention provides an operating system for manipulating the light-driven hydrogel micro / nano manipulator described in the first aspect or prepared by the method described in the second aspect. The operating system (also referred to as a drive control system) includes a near-infrared laser source, a light field modulation device, and a control unit. The near-infrared laser source provides near-infrared laser light to the light-driven hydrogel micro / nano manipulator. The light field modulation device modulates the near-infrared laser light into a dynamically programmable light pattern and irradiates the light-driven hydrogel micro / nano manipulator. The control unit controls the scanning path, irradiation time, and light intensity of the dynamically programmable light pattern. This invention triggers and controls the movement of a light-driven hydrogel micro / nano manipulator robot. In this invention, the near-infrared laser source provides near-infrared light with a wavelength of 808nm or 980nm as the driving source. The light field modulation device, for example selected from a digital micromirror device (DMD) or a galvanometer scanning system, serves as a wireless control means to modulate the light emitted by the laser source into a dynamic, programmable light pattern, which can precisely illuminate the robot's light recognition area. The control unit is connected to the light field modulation device and controls the scanning path, irradiation time, and light intensity of the light pattern, thereby triggering and controlling the robot's bending, grasping, releasing, and conveying movements, achieving non-contact, intelligent, and advanced manipulation.

[0052] The present invention provides, in its fifth aspect, the application of the light-driven hydrogel micro / nano manipulator robot described in the first aspect or the light-driven hydrogel micro / nano manipulator robot prepared by the preparation method described in the second aspect of the present invention in the field of biomedical micromanipulation or microassembly; in the present invention, the biomedical micromanipulation includes, for example, targeted drug delivery, cell manipulation, minimally invasive surgery, etc.

[0053] In this invention, when the light-driven hydrogel micro / nano manipulator is applied in biomedical micromanipulation, such as in the human body, the movement of the light-driven hydrogel micro / nano manipulator in the human body is divided into three stages: the delivery stage, in which the robot group is transported to the vicinity of the target area by an external carrier (such as an injection catheter or magnetic navigation); the navigation and execution stage, in the target area (such as tumor tissue), the robot is controlled by an operating system driven by an external light field to perform precise navigation and manipulation (such as grasping, cutting, and releasing drugs); and the recycling or degradation stage, in which the robot is biodegraded or safely excreted from the body after the task is completed.

[0054] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Unless otherwise specified, all raw materials used in the embodiments of the present invention and comparative examples can be obtained commercially or synthesized by existing methods.

[0055] Example 1 ① Preparation of Ink A (First Hydrogel Prepolymer): N-isopropylacrylamide, N-tert-butylacrylamide, N,N'-methylenebisacrylamide, photoinitiator, nanoclay, and photothermal nanomaterials are mixed evenly with water, and then ultrasonically dispersed and centrifuged to obtain Ink A. Ink A contains 1.2 mg / mL of photothermal nanomaterials, 5% nanoclay by mass, and the molar ratio of N-isopropylacrylamide to N-tert-butylacrylamide is 7. 1. The amount of N,N'-methylenebisacrylamide used is 1% of the mass of N-isopropylacrylamide; the photoinitiator is 2-hydroxy-2-methyl-1-phenyl-1-propanone, and the amount of the photoinitiator used is 0.08% of the mass of N-isopropylacrylamide; the photothermal nanomaterial is a composite of reduced graphene oxide (rGO) and carbon nanotubes (CNTs), and the composite of reduced graphene oxide and carbon nanotubes is formed by mixing reduced graphene oxide and carbon nanotubes at a mass ratio of 1:1. Preparation of Ink B (Second Hydrogel Prepolymer): N-isopropylacrylamide, acrylamide, N,N'-methylenebisacrylamide, photoinitiator, sodium alginate, and photothermal nanomaterials are mixed evenly with water, and then ultrasonically dispersed and centrifuged to obtain Ink B. Ink B contains photothermal nanomaterials at a concentration of 0.065 mg / mL, sodium alginate at a mass percentage of 1.5%, and the molar ratio of N-isopropylacrylamide to acrylamide is 10:1. The amount of N,N'-methylenebisacrylamide is 1% of the mass of N-isopropylacrylamide. The photoinitiator is 2-hydroxy-2-methyl-1-phenyl-1-propanone, and the amount of the photoinitiator is 0.08% of the mass of N-isopropylacrylamide. The photothermal nanomaterial is a composite of reduced graphene oxide (rGO) and carbon nanotubes (CNTs), and the composite of reduced graphene oxide and carbon nanotubes is formed by mixing reduced graphene oxide and carbon nanotubes in a mass ratio of 1:1.

[0056] ② Design such as Figure 2The image shown depicts a 3D model of a light-driven hydrogel micro / nano manipulator robot, comprising a light recognition area and a deformation execution area. 4D printing (microfluidic co-extrusion gradient 4D printing) was performed using inks A and B as printing materials. Ink A and B were injected into two independent feed channels of a dual-channel microfluidic co-extrusion printhead, resulting in a concentration gradient composite ink that was extruded from a micro-nozzle (80 μm in diameter) through a manifold. The model was then printed layer by layer on a low-temperature printing platform at 5°C according to a pre-set 3D model. Simultaneously with the printing and extrusion, a 365°C ultraviolet LED light source was used. The extruded gradient hydrogel filaments are simultaneously scanned and irradiated with a nanometer (nm) sensor to achieve in-situ solidification, resulting in a printed gel structure. The dual-channel microfluidic co-extrusion printhead includes an ink A channel, an ink B channel, a manifold, and a nozzle (micro-nozzle). The ink A and ink B channels are two independent feed channels, with a stable back pressure provided by a constant-pressure injection pump. Ink A enters the ink A channel from the ink A inlet, and ink B enters the ink B channel from the ink B inlet. One end of the manifold is connected to the ink A channel, and the other end is connected to the ink B channel. The middle of the manifold is connected to the nozzle. The dual-channel microfluidic co-extrusion printhead also includes piezoelectric valves disposed at the outlets of the ink A and ink B channels. The valve is controlled by a variable voltage device (voltage controller) to adjust the ratio of ink A to ink B. During the microfluidic co-extrusion gradient 4D printing process, when printing the corresponding photorecognition area, the volume feed ratio of ink A to ink B is 100:0, that is, ink B is not fed. When printing the corresponding deformation execution area, the volume feed ratio of ink A to ink B changes continuously along the printing direction, so that the volume percentage of ink A gradually decreases from 100% to 0% from the side closer to the photorecognition area to the side farther away from the photorecognition area, while the volume percentage of ink B gradually increases from 0% to 100% from the side closer to the photorecognition area to the side farther away from the photorecognition area, forming a continuously decreasing distribution of photothermal nanomaterial concentration in the corresponding deformation execution area.

[0057] ③ The printed gel structure was removed from the printing platform and soaked in deionized water for 48 hours to finally obtain a light-driven hydrogel micro-nano manipulation robot.

[0058] The volumetric phase transition temperature of the optical recognition region of the optically driven hydrogel micro / nano manipulator prepared in this embodiment is 35~40℃, and the volumetric phase transition temperature of the deformation execution region is 25~34℃.

[0059] In this invention, ink A in this embodiment was separately photocured under a UV LED light source (365nm) to obtain a hydrogel composite material, and its tensile strength was measured to be 1.38 MPa. Additionally, ink C was prepared and photocured under a UV LED light source (365nm) to obtain a hydrogel composite material, whose tensile strength was measured to be only 0.57 MPa. Ink C was prepared by uniformly mixing N-isopropylacrylamide, N-tert-butylacrylamide, N,N'-methylenebisacrylamide, a photoinitiator, and photothermal nanomaterials with water, followed by ultrasonic dispersion and centrifugal degassing to obtain ink C. Ink C contains... The concentration of the photothermal nanomaterial is 1.2 mg / mL. The molar ratio of N-isopropylacrylamide to N-tert-butylacrylamide is 7:1. The amount of N,N'-methylenebisacrylamide is 1% of the mass of N-isopropylacrylamide. The photoinitiator is 2-hydroxy-2-methyl-1-phenyl-1-propanone. The amount of the photoinitiator is 0.08% of the mass of N-isopropylacrylamide. The photothermal nanomaterial is a composite of reduced graphene oxide (rGO) and carbon nanotubes (CNTs). The composite of reduced graphene oxide and carbon nanotubes is formed by mixing reduced graphene oxide and carbon nanotubes at a mass ratio of 1:1.

[0060] In addition, the present invention separately photocured ink B in this embodiment under a UV LED light source (365nm) to obtain a hydrogel composite material, and its elongation at break was measured to be 526%. Furthermore, ink D was also prepared and photocured under a UV LED light source (365nm) to obtain a hydrogel composite material, whose elongation at break was measured to be only 175%. The preparation of ink D was as follows: N-isopropylacrylamide, acrylamide, N,N'-methylenebisacrylamide, a photoinitiator, and photothermal nanomaterials were mixed evenly with water, and then ultrasonically dispersed and centrifuged to obtain ink D. Ink D contains photothermal nanomaterials. The concentration of the nanomaterial is 0.065 mg / mL, the molar ratio of N-isopropylacrylamide to acrylamide is 10:1, the amount of N,N'-methylenebisacrylamide is 1% of the mass of N-isopropylacrylamide, the photoinitiator is 2-hydroxy-2-methyl-1-phenyl-1-propanone, the amount of the photoinitiator is 0.08% of the mass of N-isopropylacrylamide, and the photothermal nanomaterial is a composite of reduced graphene oxide (rGO) and carbon nanotubes (CNTs), which is formed by mixing reduced graphene oxide and carbon nanotubes in a mass ratio of 1:1.

[0061] The parts of this invention not described in detail are techniques known to those skilled in the art.

[0062] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A light-driven hydrogel micro / nano manipulator robot, characterized in that, The light-driven hydrogel micro / nano manipulation robot includes a micro / nano manipulation robot body, which sequentially includes a light recognition area and a deformation execution area. The photorecognition region is formed by the polymerization of a first hydrogel prepolymer containing a high concentration of photothermal nanomaterials under the action of a photoinitiator. The deformation execution region is formed by blending a first hydrogel prepolymer containing a high concentration of photothermal nanomaterials and a second hydrogel prepolymer containing a low concentration of photothermal nanomaterials in different proportions and polymerizing them under the action of a photoinitiator, so that the concentration of photothermal nanomaterials in the deformation execution region gradually decreases from the side closer to the photorecognition region to the side farther away from the photorecognition region.

2. The light-driven hydrogel micro / nano manipulator robot according to claim 1, characterized in that: The first hydrogel prepolymer contains N-isopropylacrylamide, N-tert-butylacrylamide, N,N'-methylenebisacrylamide, a photoinitiator, nanoclay, photothermal nanomaterials, and water. The concentration of photothermal nanomaterials in the first hydrogel prepolymer is 1.0 mg / mL to 1.5 mg / mL, the mass percentage of nanoclay in the first hydrogel prepolymer is 4 wt% to 6 wt%, and / or the molar ratio of N-isopropylacrylamide to N-tert-butylacrylamide in the first hydrogel prepolymer is (5~10):1; and / or The second hydrogel prepolymer contains N-isopropylacrylamide, acrylamide, N,N'-methylenebisacrylamide, a photoinitiator, sodium alginate, photothermal nanomaterials, and water. The concentration of photothermal nanomaterials in the second hydrogel prepolymer is 0.05 mg / mL to 0.1 mg / mL. The mass percentage of sodium alginate in the second hydrogel prepolymer is 1 wt% to 2 wt%. And / or the molar ratio of N-isopropylacrylamide to acrylamide in the second hydrogel prepolymer is (8~12):

1.

3. The light-driven hydrogel micro / nano manipulator robot according to claim 1, characterized in that: The photothermal nanomaterial is a composite of reduced graphene oxide and carbon nanotubes, preferably with a mass ratio of reduced graphene oxide to carbon nanotubes of (0.5~2):1; and / or When forming the deformation execution area, the first hydrogel prepolymer and the second hydrogel prepolymer are blended in different ratios by microfluidic co-extrusion. Preferably, the ratio of the first hydrogel prepolymer to the second hydrogel prepolymer changes continuously from 100:0 to 0:100 along the microfluidic co-extrusion direction.

4. The light-driven hydrogel micro / nano manipulator robot according to claim 1, characterized in that: The micro-nano manipulation robot body has a biomimetic structure, preferably a micro-clamping structure, a micro-hand structure, a micro-basket structure, or a crab-like structure.

5. The light-driven hydrogel micro / nano manipulator robot according to claim 1, characterized in that: The volume phase transition temperature of the optical recognition region is 35~40℃; The volume phase transition temperature of the deformation execution region is lower than that of the optical recognition region, and the volume phase transition temperature range of the deformation execution region is greater than that of the optical recognition region. and / or The deformation execution region is loaded with pH-responsive hydrogel and / or drug molecules.

6. A method for fabricating a light-driven hydrogel micro / nano manipulator according to any one of claims 1 to 5, characterized in that, The method includes the following steps: (1) Prepare the first hydrogel prepolymer as ink A, and prepare the second hydrogel prepolymer as ink B; (2) Design a printing model of a light-driven hydrogel micro-nano manipulation robot, which includes a light recognition area and a deformation execution area in sequence. Use ink A and ink B as printing materials for 4D printing. The printing head used in the 4D printing is a multi-channel microfluidic co-extrusion printing head. During the 4D printing process, the ratio of ink A and ink B in the multi-channel microfluidic co-extrusion printing head is adjusted to carry out the 4D printing of the light-driven hydrogel micro-nano manipulation robot, and the light-driven hydrogel micro-nano manipulation robot is obtained.

7. The preparation method according to claim 6, characterized in that: The multi-channel microfluidic co-extrusion printhead includes an ink A channel, an ink B channel, a manifold, and a nozzle; One end of the manifold is connected to the ink A channel, and the other end is connected to the ink B channel. The middle part of the manifold is connected to the nozzle. The multi-channel microfluidic co-extrusion printhead also includes a microfluidic valve for controlling the ratio of ink A and ink B. Preferably, the multi-channel microfluidic co-extrusion printhead also includes a piezoelectric valve disposed at the outlet of the ink A channel and the ink B channel. The piezoelectric valve is controlled by a variable voltage electric device to achieve the adjustment of the ratio of ink A and ink B. Preferably, the diameter of the nozzle is 50-200 μm; Preferably, the temperature of the printing platform is 4~10℃ during 4D printing; Preferably, when performing 4D printing, an ultraviolet LED light source is used to irradiate the printing platform; Preferably, the ultraviolet LED light source used emits ultraviolet light with a wavelength of 365~405nm.

8. A multi-channel microfluidic co-extrusion printhead, characterized in that, The multi-channel microfluidic co-extrusion printhead is used to implement the preparation method described in claim 6 or 7, and the multi-channel microfluidic co-extrusion printhead includes an ink A channel, an ink B channel, a manifold, and a nozzle; One end of the manifold is connected to the ink A channel, and the other end is connected to the ink B channel. The middle part of the manifold is connected to the nozzle. The multi-channel microfluidic co-extrusion printhead also includes a microfluidic valve for controlling the ratio of ink A and ink B. Preferably, the multi-channel microfluidic co-extrusion printhead also includes a piezoelectric valve disposed at the outlet of the ink A channel and the ink B channel. The piezoelectric valve is controlled by a variable voltage device to achieve the adjustment of the ratio of ink A and ink B.

9. An operating system for manipulating the light-driven hydrogel micro / nano manipulator robot according to any one of claims 1 to 5 or the light-driven hydrogel micro / nano manipulator robot prepared by the preparation method according to claim 6 or 7, characterized in that, The operating system includes a near-infrared laser source, a light field modulation device, and a control unit. The near-infrared laser source is used to provide near-infrared laser light to the light-driven hydrogel micro / nano manipulator. The light field modulation device is used to modulate the near-infrared laser light into a dynamically programmable light pattern and irradiate it onto the light-driven hydrogel micro / nano manipulator. The control unit is used to control the scanning path, irradiation time, and light intensity of the dynamically programmable light pattern to trigger and control the movement of the light-driven hydrogel micro / nano manipulator.

10. The application of the light-driven hydrogel micro / nano manipulator robot according to any one of claims 1 to 5 or the light-driven hydrogel micro / nano manipulator robot prepared by the preparation method according to claim 6 or 7 in the field of biomedical micromanipulation or microassembly.

Images