Microneedle preparation system with stepped tip

Abstract

The invention discloses a microneedle preparation system with a stepped tail end, and belongs to the technical field of micro-nano manufacturing. The invention aims to solve the problem of low efficiency of an existing preparation method of a microneedle with a stepped tail end. Comprising the following steps: obtaining a collimated metal wire through a metal wire pretreatment unit; feeding of the collimated metal wire in the axial direction is achieved through the metal wire clamping unit, so that the metal wire is assembled into the metal tube, and an initial microneedle structure with a stepped tail end is formed; the pose of the metal tube is adjusted to correspond to the collimated metal wire through the metal tube clamping unit, so that the collimated metal wire is inserted into the metal tube after being fed in the axial direction of the metal tube; acquiring relative attitude information of the collimated metal wire and the metal tube through a visual feedback unit, and feeding back the relative attitude information to a metal wire clamping unit; and performing electrochemical etching on the metal wire section at the step-shaped tail end of the initial microneedle structure through the tail end processing unit to realize the forming of the tip of the microneedle and finish the preparation of the microneedle. The method is used for preparing the microneedle with the stepped tail end.

Description

Technical Field

[0001] The invention relates to a microneedle preparation system with a stepped end, belonging to the technical field of micro-nano manufacturing. Background Art

[0002] With the rapid development of microelectronics technology, the demand for microneedles with stepped end structures in the field of precision microdevice operations is growing. For example, in applications such as flexible electrode implantation in the field of brain-computer interface, microneedles with stepped ends can achieve precise grasping, delivery and release of flexible microdevices. This places higher demands on the manufacturing accuracy and reliability of the microneedle end structure.

[0003] At present, the following technical solutions are mainly used to prepare microneedles with stepped ends: one is focused ion beam processing technology, which requires the use of special equipment and has high equipment investment and maintenance costs; the other is femtosecond laser processing technology, which also has problems such as low processing efficiency and high equipment costs. Both solutions are difficult to meet the needs of efficient production.

[0004] In order to solve the above problems, a technical solution for realizing microneedle microassembly has emerged. This microassembly method has the potential to realize high-precision microstructures. However, this microassembly technology has extremely high requirements for assembly accuracy and must rely on complex force feedback control systems and high-precision force sensors. This not only increases the complexity of the system, but also makes the assembly process cumbersome and time-consuming. In addition, in the process of high-precision alignment of microneedles, the slightest carelessness may cause damage to parts, reducing production efficiency.

[0005] Although the micro-assembly process uses flexible clamps, it still faces many challenges in achieving accurate assembly of stepped end structures. For example, positional deviations during assembly are difficult to effectively control, workpieces are prone to deformation or damage due to the difficulty in accurately controlling the clamping force, and there is a lack of targeted automated control strategies. These technical issues make it difficult to ensure the accuracy and consistency of the manufactured components, affecting the quality of the final product.

[0006] In summary, the existing technologies have deficiencies in assembly precision control, workpiece protection, and automated control strategies, which lead to reduced component quality and production efficiency. These problems need to be solved urgently to meet the needs of efficient production of microneedles with stepped ends. Summary of the invention

[0007] In view of the problem that the existing method for preparing microneedles with stepped ends is inefficient, the present invention provides a system for preparing microneedles with stepped ends.

[0008] A microneedle preparation system with a stepped end of the present invention comprises:

[0009] A metal wire pretreatment unit is used to stretch the metal wire in a heated state to release internal stress and obtain a straightened metal wire;

[0010] The wire clamping unit is used to clamp the collimated wire and dynamically adjust the clamping position of the collimated wire to change the stiffness of the collimated wire; at the same time, based on the relative posture information fed back by the visual feedback unit, the position and stiffness of the collimated wire are adjusted, and the collimated wire is fed along its axial direction to be assembled into the metal tube to form an initial microneedle structure with a stepped end;

[0011] The metal tube clamping unit is used to clamp the metal tube and adjust the posture of the metal tube to correspond to the collimated metal wire, so that the collimated metal wire is fed along its axial direction and inserted into the metal tube;

[0012] A visual feedback unit, used to obtain the relative posture information of the metal wire and the metal tube after alignment, and feed it back to the metal wire clamping unit;

[0013] The end processing unit is used to electrochemically etch the metal wire segment at the stepped end of the initial microneedle structure to achieve the molding of the microneedle tip and complete the preparation of the microneedle.

[0014] According to the microneedle preparation system with stepped ends of the present invention, the axial direction of the aligned metal wire is taken as the X-axis direction;

[0015] The visual feedback unit includes a Y-axis camera and a Z-axis camera, which are used to respectively obtain the Y-axis viewing angle relative posture image and the Z-axis viewing angle relative posture image of the collimated metal wire and the metal tube, and obtain the relative posture information of the collimated metal wire and the metal tube based on image processing.

[0016] According to the microneedle preparation system with stepped ends of the present invention, the metal wire clamping unit realizes assembly control of the metal wire and the metal tube after alignment based on a finite state machine; the finite state machine performs state transfer and control strategy switching according to the relative posture information fed back by the visual feedback unit, including:

[0017] Separation state: adjust and control the clamping point of the metal wire clamping unit to align the clamped metal wire with the metal tube along the X-axis direction and feed along the X-axis direction; make the length L of the metal microwire inserted into the metal microtube after alignment inserted From the current state at the initial moment L inserted = 0 to the end time L inserted →0;

[0018] Low-rigidity contact state: Control the wire clamping unit to continue feeding along the X-axis direction; make the end of the metal microwire and the head of the metal tube realize low-stress contact after low-rigidity state alignment; from the initial moment of the current state σ<σ s Until the end time σ→σs ; L inserted →0; where σ is the internal stress of the wire, σ s is the maximum stress of the wire;

[0019] Low-rigidity stuck state: Control the wire clamping unit to continue feeding along the X-axis direction; make the end of the metal microwire after low-rigidity state alignment and the head end of the metal tube achieve high-stress contact; from the initial moment of the current state σ→σ s , L inserted →0 to the end time σ<σ s , L inserted >>0;

[0020] High-rigidity contact state: adjust and control the clamping point of the wire clamping unit to the aligned wire, and control the wire clamping unit to continue feeding along the X-axis direction; so that the end of the aligned metal microwire in the high-rigidity state can be inserted into the head of the metal tube with low stress; from the initial moment of the current state σ<σ s Until the end time σ→σ s ; L inserted >>0;

[0021] High-rigidity stuck state: Control the wire clamping unit to continue feeding along the X-axis direction; make the end of the metal microwire and the head of the metal tube realize high-stress insertion after high-rigidity state alignment; from the initial moment of the current state σ→σ s At the end time, σ=0; L inserted >>0;

[0022] Release state: control the wire clamping unit to release the aligned wire, σ=0.

[0023] According to the microneedle preparation system with stepped ends of the present invention, in the separation state, the low-rigidity contact state and the low-rigidity stuck state, the equivalent stiffness of the aligned metal microwire is reduced by increasing the distance between the clamping point of the aligned metal wire and the end of the aligned metal wire by the metal wire clamping unit; the elastic deformation of the aligned metal microwire is used to realize the passive compensation of the position error of the end of the aligned metal wire;

[0024] In the high-rigidity contact state and the high-rigidity stuck state, the equivalent stiffness of the aligned metal microwire is increased by reducing the distance between the clamping point of the metal wire clamping unit on the aligned metal wire and the end of the aligned metal wire, thereby overcoming the insertion resistance.

[0025] According to the microneedle preparation system with a stepped end of the present invention, the wire clamping unit includes a clamping member, a wire YZ axis adjustment mechanism and a linear translation stage. The clamping member clamps the aligned wire through a flexible hinge clamp, the clamping member is arranged on the YZ axis adjustment mechanism, and the YZ axis adjustment mechanism is arranged on the linear translation stage; the linear translation stage has the function of moving along the X-axis direction.

[0026] According to the microneedle preparation system with stepped ends of the present invention, the control quantity of the finite state machine for state transition includes the distance δ between the end of the metal microwire and the head end of the metal tube after alignment. e , the angle θ between the metal microwire and the metal tube after alignment and the visible length of the metal wire in the visual feedback unit field of view

[0027] The condition from the separation state to the low stiffness contact state is δ e =0;

[0028] The condition from the low-stiffness contact state to the low-stiffness stuck state is θ→0;

[0029] The condition from high stiffness contact state to high stiffness stuck state is the visible length per unit time The change ΔL is less than 40-60% of the feed amount Δx of the metal microwire along the X-axis direction after alignment;

[0030] At the end of the low-rigidity stuck state and the high-rigidity stuck state, the flexible hinge clamp releases the collimated metal wire, and the linear translation stage moves in the opposite direction of the feeding direction to enter the release state;

[0031] In the released state, the linear translation stage is moved along the feeding direction, so that the flexible hinge clamp clamps the aligned wire; if θ>θc, or δ e ≠0, it enters the separation state; where θc is the limit horizontal angle at which the metal wire does not undergo plastic deformation after collimation.

[0032] According to the microneedle preparation system with a stepped end of the present invention, the metal tube clamping unit includes a metal tube YZ-axis adjustment mechanism and an adjustment mechanism greater than five axes. The metal tube YZ-axis adjustment mechanism is arranged on the adjustment mechanism greater than five axes. A clamping hole is arranged at the center of the metal tube YZ-axis adjustment mechanism for clamping the metal tube so that the axial direction of the metal tube is along the X-axis direction.

[0033] According to the microneedle preparation system with stepped ends of the present invention, in the wire pretreatment unit, the heating temperature of the wire is 1300-1500°C, and the temperature is controlled by a heating current; the wire is in a vacuum or inert gas atmosphere, and the tensile force is 0.5-5N.

[0034] According to the microneedle preparation system with a stepped end of the present invention, the end processing unit uses an alkaline etching solution with a concentration of 2-4 mol / L to electrochemically etch the metal wire segment with the stepped end; the etching voltage is 4-8V, and the etching current is monitored by a series resistor. When the etching current decreases from 80-90% of the initial value to 10-20%, the power is cut off.

[0035] According to the microneedle preparation system with stepped ends of the present invention, the length of the microneedle tip after electrochemical etching is 0.2 to 10 times the diameter of the metal wire.

[0036] Beneficial effects of the present invention: The system of the present invention prepares microneedles with stepped ends based on the assembly of universal components, does not rely on special equipment, and can significantly reduce manufacturing costs; variable stiffness control of metal wires based on visual feedback can effectively simplify the assembly process and improve the assembly success rate; the system of the present invention uses visual guidance for automated assembly control, which can ensure the accuracy and consistency of the microneedle products. The system of the present invention can achieve efficient and low-cost manufacturing of microneedles with stepped ends, laying a reliable technical foundation for their wide application in the field of precision operations.

[0037] The microneedles prepared by the system of the present invention can be used for precise implantation and manipulation of flexible microdevices, and have broad application prospects in the fields of biomedicine, microelectronics, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 Schematic diagram of a microneedle structure prepared by using the microneedle preparation system with a stepped end of the present invention; the dotted line frame in the figure is the stepped structure of the microneedle end;

[0039] Figure 2 Schematic diagram of the metal wire pretreatment unit treating the metal wire; pull Indicates the wire stretching distance, U heat Represents the voltage applied across the wire, F pull Indicates the tension applied at both ends of the wire obtained by the tension sensor;

[0040] Figure 3 It is a schematic diagram of assembling by changing the stiffness of the aligned wire through the clamping point; grip The horizontal distance between the clamping point of the wire clamping unit and the head end of the metal tube after the wire is aligned;

[0041] Figure 4 Schematic diagram of electrochemical etching performed by the terminal processing unit; etch is the current of the electrochemical corrosion circuit, U etch is the voltage applied across the wire and the series resistor;

[0042] Figure 5 It is a schematic diagram of the cooperation of the metal wire clamping unit, the metal tube clamping unit and the visual feedback unit for microneedle assembly;

[0043] Figure 6 is a schematic diagram of the separation state of the metal wire and the metal tube after alignment under the control of the finite state machine;

[0044] Figure 7is a schematic diagram of the low-rigidity contact state between the metal wire and the metal tube after alignment under the control of a finite state machine;

[0045] Figure 8 It is a schematic diagram of the low-rigidity stuck state of the metal wire and the metal tube after alignment under the control of the finite state machine;

[0046] Fig. 9 It is a schematic diagram of the high-rigidity contact state between the metal wire and the metal tube after alignment under the control of the finite state machine;

[0047] Fig.10 It is a schematic diagram of the high-rigidity stuck state of the metal wire and the metal tube after alignment under the control of the finite state machine;

[0048] Fig.11 is a schematic diagram of the release state of the metal wire and the metal tube after alignment under the control of the finite state machine;

[0049] Fig.12 It is a schematic diagram of the state switching control of the finite state machine; in the figure, μ represents The ratio between the change ΔL and the feed amount Δx, L th Indicates the set insertion length threshold;

[0050] Fig.13 Schematic diagram of the process of implanting the prepared microneedle-operated flexible neural electrode into an agar phantom;

[0051] Fig.14 This is an electron microscope image of the microneedle after the flexible neural electrode is implanted into the agar phantom. DETAILED DESCRIPTION

[0052] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0053] It should be noted that, in the absence of conflict, the embodiments of the present invention and the features in the embodiments may be combined with each other.

[0054] The present invention will be further described below in conjunction with the accompanying drawings and specific embodiments, but they are not intended to limit the present invention.

[0055] Specific implementation method 1. Combination Figures 1 to 5 As shown, the present invention provides a microneedle preparation system with a stepped end, comprising:

[0056] The metal wire pretreatment unit 100 is used to stretch the metal wire in a heated state to release the internal stress and obtain the aligned metal wire 110; it includes a temperature control loop and a stress control loop, which are used to control the heating current and the stretching stress respectively;

[0057] The metal wire clamping unit 200 is used to clamp the collimated metal wire 110, and dynamically adjust the clamping position of the collimated metal wire 110 to change the stiffness of the collimated metal wire; at the same time, based on the relative posture information fed back by the visual feedback unit 400, the posture and stiffness of the collimated metal wire are adjusted, and the collimated metal wire 110 is fed along its axial direction to be assembled into the metal tube 310 to form an initial microneedle structure with a stepped end;

[0058] The metal tube clamping unit 300 is used to clamp the metal tube 310 and adjust the posture of the metal tube to correspond to the collimated metal wire 110, so that the collimated metal wire 110 is fed along its axial direction and inserted into the metal tube 310;

[0059] A visual feedback unit 400 is used to obtain relative posture information of the metal wire 110 and the metal tube 310 after alignment, and feed it back to the metal wire clamping unit 200;

[0060] The end processing unit 500 is used to electrochemically etch the metal wire segment at the stepped end of the initial microneedle structure to achieve the molding of the microneedle tip and complete the preparation of the microneedle.

[0061] The wire pretreatment unit 100 adopts stress closed-loop control, and releases the internal stress of the wire by heating and stretching it, so as to achieve the purpose of alignment; the wire clamping unit 200 realizes the controllable change of the stiffness of the wire in the assembly section by dynamically adjusting the clamping position, and adopts a visual feedback system for real-time posture monitoring and compensation control; the terminal processing unit 500 adopts an electrochemical etching method, and realizes the precise shaping of the microneedle tip by monitoring the current change. The wire is placed in an electrolyte for electrochemical etching; the etching process is controlled by monitoring the etching current change; the etching is stopped when the etching current changes by a preset value.

[0062] In this embodiment, combined with Figure 5 As shown, the axial direction of the collimated metal wire 110 is taken as the X-axis direction;

[0063] The visual feedback unit 400 includes a Y-axis camera 410 and a Z-axis camera 420, which are used to respectively obtain the Y-axis perspective relative posture image and the Z-axis perspective relative posture image of the collimated metal wire 110 and the metal tube 310, and obtain the relative posture information of the collimated metal wire 110 and the metal tube 310 based on image processing.

[0064] The Y-axis camera 410 and the Z-axis camera 420 are disposed perpendicular to each other and are used to obtain the relative posture information between the metal wire and the metal tube in real time.

[0065] Further, combined with Figures 6 to 12 As shown, the wire clamping unit 200 realizes assembly control of the collimated wire 110 and the metal tube 310 based on a finite state machine; the finite state machine performs state transfer and control strategy switching according to the relative posture information fed back by the visual feedback unit 400, including:

[0066] Separation state: adjust and control the clamping point of the metal wire clamping unit 200 to align the clamped metal wire 110 with the metal tube 310 along the X-axis direction and feed along the X-axis direction; insert the metal microwire 110 into the metal microtube 310 by a length L inserted From the current state at the initial moment L inserted = 0 to the end time L inserted →0;

[0067] Low-rigidity contact state: Control the wire clamping unit 200 to continue feeding along the X-axis direction; make the end of the metal microwire 110 and the head end of the metal tube 310 realize low-stress contact after low-rigidity state alignment; from the initial moment of the current state σ<σ s Until the end time σ→σ s ; L inserted →0; where σ is the internal stress of the wire, σ s is the maximum stress of the wire; σ s Less than 80% of its plastic deformation limit stress;

[0068] Low-rigidity stuck state: Control the wire clamping unit 200 to continue feeding along the X-axis direction; make the end of the metal microwire 110 and the head end of the metal tube 310 realize high-stress contact after low-rigidity state alignment; from the initial moment of the current state σ→σ s , L inserted →0 to the end time σ<σ s , L inserted >>0;

[0069] High-rigidity contact state: adjust and control the clamping point of the metal wire clamping unit 200 to the aligned metal wire 110, and control the metal wire clamping unit 200 to continue feeding along the X-axis direction; so that the end of the aligned metal microwire 110 in the high-rigidity state and the head end of the metal tube 310 can be inserted with low stress; from the initial moment of the current state σ<σ s Until the end time σ→σ s ; L inserted >>0;

[0070] High-rigidity stuck state: Control the wire clamping unit 200 to continue feeding along the X-axis direction; make the end of the metal microwire 110 and the head of the metal tube 310 in the high-rigidity state collimated to achieve high-stress insertion; from the initial moment of the current state σ→σ s At the end time, σ=0; L inserted >>0;

[0071] Release state: the wire clamping unit 200 is controlled to release the aligned wire 110, σ=0.

[0072] Figures 6 to 11 As shown in FIG. 1 , it is a schematic diagram of performing posture position analysis based on the image obtained by the visual feedback unit 400. It can be seen that the dynamic adjustment of the clamping position changes L grip Controllable variation of wire stiffness can be achieved.

[0073] In this embodiment, the assembly process of the microneedle includes two stages: low-rigidity alignment and high-rigidity insertion:

[0074] In the separation state, the low-rigidity contact state and the low-rigidity stuck state, the equivalent stiffness of the aligned metal microwire 110 is reduced by increasing the distance between the clamping point of the metal wire clamping unit 200 and the end of the aligned metal wire 110; the elastic deformation of the aligned metal microwire 110 is used to realize the passive compensation of the position error of the end of the aligned metal wire 110;

[0075] In the high-rigidity contact state and the high-rigidity stuck state, i.e., the high-rigidity insertion stage, the equivalent stiffness of the aligned metal microwire 110 is increased by reducing the distance between the clamping point of the metal wire clamping unit 200 on the aligned metal wire 110 and the end of the aligned metal wire 110, thereby overcoming the insertion resistance and achieving precise assembly.

[0076] Combination Figure 5 As shown, the wire clamping unit 200 includes a clamping member 210, a wire YZ axis adjustment mechanism 220 and a linear translation stage 230. The clamping member 210 clamps the aligned wire 110 through a flexible hinge clamp. The clamping member 210 is arranged on the YZ axis adjustment mechanism 220, and the YZ axis adjustment mechanism 220 is arranged on the linear translation stage 230. The linear translation stage 230 has the function of moving along the X-axis direction.

[0077] Going a step further, combined Figures 6 to 12 As shown, the control quantity of the finite state machine for state transfer includes the distance δ between the end of the metal microwire 110 and the head end of the metal tube 310 after alignment. e , the angle θ between the metal microwire 110 and the metal tube 310 after alignment and the visible length of the metal wire in the field of view of the visual feedback unit 400

[0078] The condition from the separation state to the low stiffness contact state is δe =0; its actual judgment is δ e Less than 0.1-0.5 times the wire diameter, preferably 0.2 times;

[0079] The condition for changing from the low-rigidity contact state to the low-rigidity stuck state is θ→0; the actual judgment condition is that θ is less than 0.3-0.8°, preferably 0.5°;

[0080] The condition from high stiffness contact state to high stiffness stuck state is the visible length per unit time The change ΔL is less than 40-60% of the feed amount Δx of the metal microwire 110 along the X-axis direction after alignment;

[0081] At the end of the low-rigidity stuck state and the high-rigidity stuck state, the flexible hinge clamp releases the collimated metal wire 110, and the linear translation stage 230 moves in the opposite direction of the feeding direction to enter the release state;

[0082] In the released state, the linear translation stage 230 is moved along the feeding direction, so that the flexible hinge clamp clamps the aligned metal wire 110; if θ>θc, or δ e ≠0, it enters the separation state; where θc is the limit horizontal angle at which the collimated metal wire 110 does not undergo plastic deformation. After entering the separation state, the flexible hinge clamp clamps the collimated metal wire again, and the linear translation stage 230 moves along the feeding direction.

[0083] Going a step further, combined Figure 5 As shown, the metal tube clamping unit 300 includes a metal tube YZ axis adjustment mechanism 320 and an adjustment mechanism 330 greater than five axes. The metal tube YZ axis adjustment mechanism 320 is arranged on the adjustment mechanism 330 greater than five axes. A clamping hole is arranged at the center of the metal tube YZ axis adjustment mechanism 320 for clamping the metal tube 310 so that the metal tube 310 is axially along the X-axis direction.

[0084] As an example, in the wire pretreatment unit 100 , the heating temperature of the wire is 1300-1500° C., and the temperature is controlled by a heating current; the wire is in a vacuum or inert gas atmosphere, and the tensile force is 0.5-5N.

[0085] As an example, the stretching force is preferably 1-3N to ensure that the internal stress of the metal wire is evenly distributed during the heating and stretching process.

[0086] In actual use, the heating temperature and the stretching force are set according to the material properties of the metal wire to achieve the release of stress within the metal wire.

[0087] As an example, the end processing unit 500 uses an alkaline etching solution with a concentration of 2-4 mol / L to electrochemically etch the metal wire segment at the stepped end; the etching voltage is 4-8V, and the etching current is monitored by a series resistor. When the etching current drops from 80-90% of the initial value to 10-20%, the power is cut off.

[0088] As an example, the concentration of the alkaline etching solution is 3 mol / L, and the etching voltage is 6 V. The alkaline etching solution may be a KOH solution.

[0089] As an example, the length of the electrochemically etched microneedle tip is 0.2 to 10 times, preferably 0.5 to 2 times, the diameter of the metal wire.

[0090] Application experiment:

[0091] like Fig.13 As shown, the process of microneedle operation of flexible neural electrode, firstly, the alignment action is performed, so that the end of the microneedle is placed in the coaxial sleeve 600, and the stepped end of the microneedle is aligned with the operation hole of the flexible electrode 700; then the operation task is performed: the microneedle moves downward in the coaxial sleeve 600, so that the needle tip part enters the operation hole and the step part is outside the operation hole, driving the flexible electrode 700 to be peeled off from the substrate 800, implanted into the brain tissue phantom prepared with 0.6% agar, and reaches the specified depth; then the withdrawal task is performed: the microneedle is withdrawn, so that the flexible electrode 700 is left in the brain tissue phantom. After the microneedle is withdrawn, the flexible electrode only changes by about 32μm in the brain tissue phantom, which is equivalent to the size of a neuron cell, indicating that the microneedle manufactured by the present invention can accurately implant the flexible electrode into the specified position in the brain tissue cube. Fig.14 This is an electron microscope image of multiple microneedles manufactured by the system of the present invention after multiple experiments.

[0092] Although the present invention is described herein with reference to specific embodiments, it should be understood that these embodiments are merely examples of the principles and applications of the present invention. It should therefore be understood that many modifications may be made to the exemplary embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as defined by the appended claims. It should be understood that the various dependent claims and features described herein may be combined in a manner different from that described in the original claims. It should also be understood that the features described in conjunction with a single embodiment may be used in other described embodiments.

Claims

1. A system for preparing microneedles with stepped ends, characterized in that: include, A metal wire pretreatment unit (100) is used to stretch the metal wire in a heated state to release internal stress and obtain a collimated metal wire (110); The metal wire clamping unit (200) is used to clamp the collimated metal wire (110) and dynamically adjust the clamping position of the collimated metal wire (110) to change the stiffness of the collimated metal wire; at the same time, based on the relative posture information fed back by the visual feedback unit (400), the position and stiffness of the collimated metal wire are adjusted, and the collimated metal wire (110) is fed along its axial direction so that it is assembled into the metal tube (310) to form an initial microneedle structure with a stepped end; The metal tube clamping unit (300) is used to clamp the metal tube (310) and adjust the posture of the metal tube to correspond to the collimated metal wire (110), so that the collimated metal wire (110) is fed along its axial direction and then inserted into the metal tube (310); A visual feedback unit (400) is used to obtain relative posture information of the metal wire (110) and the metal tube (310) after alignment, and feed the information back to the metal wire clamping unit (200); The end processing unit (500) is used to electrochemically etch the metal wire segment at the stepped end of the initial microneedle structure to achieve the molding of the microneedle tip and complete the preparation of the microneedle.

2. The microneedle preparation system with stepped ends according to claim 1, characterized in that: The axial direction of the collimated metal wire (110) is taken as the X-axis direction; The visual feedback unit (400) comprises a Y-axis camera (410) and a Z-axis camera (420), which are used to respectively obtain a Y-axis viewing angle relative posture image and a Z-axis viewing angle relative posture image of the collimated metal wire (110) and the metal tube (310), and obtain relative posture information of the collimated metal wire (110) and the metal tube (310) based on image processing.

3. The microneedle preparation system with stepped ends according to claim 2, characterized in that: The metal wire clamping unit (200) realizes assembly control of the collimated metal wire (110) and the metal tube (310) based on a finite state machine; The finite state machine performs state transfer and control strategy switching according to the relative posture information fed back by the visual feedback unit (400), including: Separated state: adjusting and controlling the clamping point of the metal wire clamping unit (200) on the aligned metal wire (110) so that the clamped aligned metal wire (110) is aligned with the metal tube (310) along the X-axis direction and is fed along the X-axis direction; The length L of the aligned metal microwire (110) inserted into the metal microtube (310) inserted From the current state at the initial moment L inserted = 0 to the end time L inserted →0; Low-rigidity contact state: control the metal wire clamping unit (200) to continue feeding along the X-axis direction; make the end of the metal microwire (110) and the head end of the metal tube (310) realize low-stress contact after low-rigidity state alignment; from the initial moment of the current state σ<σ s Until the end time σ→σ s ; L inserted →0; where σ is the internal stress of the wire, σ s is the maximum stress of the wire; Low-rigidity stuck state: control the metal wire clamping unit (200) to continue feeding along the X-axis direction; make the end of the metal microwire (110) after low-rigidity state alignment and the head end of the metal tube (310) achieve high-stress contact; from the initial moment of the current state σ→σ s , L inserted →0 to the end time σ<σ s , L inserted >>0; High-rigidity contact state: adjusting and controlling the metal wire clamping unit (200) to clamp the metal wire (110) after alignment, and controlling the metal wire clamping unit (200) to continue feeding along the X-axis direction; achieving low-stress insertion between the end of the metal microwire (110) after alignment in the high-rigidity state and the head end of the metal tube (310); and adjusting the current state from the initial moment of σ<σ s Until the end time σ→σ s ; L inserted >>0; High-rigidity stuck state: controlling the metal wire clamping unit (200) to continue feeding along the X-axis direction; achieving high-stress insertion between the end of the metal microwire (110) and the head end of the metal tube (310) after being aligned in the high-rigidity state; and changing the current state from σ at the initial moment to σ s At the end time, σ=0; L inserted >>0; Release state: the metal wire clamping unit (200) is controlled to release the collimated metal wire (110), σ=0.

4. The microneedle preparation system with stepped ends according to claim 3, characterized in that: In the separation state, the low-rigidity contact state and the low-rigidity stuck state, the equivalent stiffness of the collimated metal microwire (110) is reduced by increasing the distance between the clamping point of the metal wire clamping unit (200) on the collimated metal wire (110) and the end of the collimated metal wire (110); and the elastic deformation of the collimated metal microwire (110) is used to realize passive compensation of the position error of the end of the collimated metal wire (110); In the high-rigidity contact state and the high-rigidity stuck state, the equivalent rigidity of the aligned metal microwire (110) is increased by reducing the distance between the clamping point of the metal wire clamping unit (200) on the aligned metal wire (110) and the end of the aligned metal wire (110), thereby overcoming the insertion resistance.

5. The microneedle preparation system with stepped ends according to claim 4, characterized in that: The metal wire clamping unit (200) comprises a clamping member (210), a metal wire YZ axis adjustment mechanism (220) and a linear displacement platform (230); the clamping member (210) clamps the collimated metal wire (110) through a flexible hinge clamping jaw; the clamping member (210) is arranged on the YZ axis adjustment mechanism (220); the YZ axis adjustment mechanism (220) is arranged on the linear displacement platform (230); and the linear displacement platform (230) has the function of moving along the X axis direction.

6. The microneedle preparation system with stepped ends according to claim 5, characterized in that: The control quantity of the finite state machine for state transfer includes the distance δ between the end of the metal microwire (110) and the head end of the metal tube (310) after alignment. e , the angle θ between the metal microwire (110) and the metal tube (310) after alignment, and the visible length of the metal wire in the field of view of the visual feedback unit (400) The condition from the separation state to the low stiffness contact state is δ e =0; The condition from the low-stiffness contact state to the low-stiffness stuck state is θ→0; The condition from high stiffness contact state to high stiffness stuck state is the visible length per unit time The change ΔL is less than 40-60% of the feed amount Δx of the metal microwire (110) along the X-axis direction after alignment; At the end of the low-rigidity stuck state and the high-rigidity stuck state, the flexible hinge clamp releases the collimated rear metal wire (110), and the linear displacement stage (230) moves in the opposite direction of the feeding direction to enter a released state; In the released state, the linear displacement stage (230) is moved along the feeding direction, so that the flexible hinge clamping claw clamps the collimated metal wire (110); if θ>θc, or δ e ≠0, it enters the separation state; where θc is the limit horizontal angle at which the metal wire (110) does not undergo plastic deformation after alignment.

7. The microneedle preparation system with stepped ends according to claim 1, characterized in that: The metal tube clamping unit (300) comprises a metal tube YZ axis adjustment mechanism (320) and a five-axis adjustment mechanism (330). The metal tube YZ axis adjustment mechanism (320) is arranged on the five-axis adjustment mechanism (330). A clamping hole is arranged at the center of the metal tube YZ axis adjustment mechanism (320) for clamping the metal tube (310) so that the axial direction of the metal tube (310) is along the X-axis direction.

8. The microneedle preparation system with stepped ends according to claim 1, characterized in that: In the metal wire pretreatment unit (100), the heating temperature of the metal wire is 1300-1500°C, and the temperature is controlled by a heating current; the metal wire is in a vacuum or inert gas atmosphere, and the tensile force is 0.5-5N.

9. The microneedle preparation system with stepped ends according to claim 1, characterized in that: The terminal processing unit (500) uses an alkaline etching solution with a concentration of 2-4 mol / L to electrochemically etch the metal wire segment at the stepped terminal; The etching voltage is 4-8V, and the etching current is monitored by a series resistor. When the etching current decreases from 80-90% of the initial value to 10-20%, the power supply is cut off.

10. The microneedle preparation system with stepped ends according to claim 1, characterized in that: The length of the electrochemically etched microneedle tip is 0.2 to 10 times the diameter of the metal wire.

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