Microneedle preparation system with stepped tips

Abstract

A system for preparing microneedles with stepped ends belongs to the field of micro-nano manufacturing technology. The present invention addresses the problem of low efficiency of existing methods for preparing microneedles with stepped ends. It comprises: obtaining a collimated metal wire through a metal wire pre-processing unit; feeding the collimated metal wire along its axial direction through a metal wire clamping unit, so that it is assembled into a metal tube to form an initial microneedle structure with a stepped end; adjusting the posture of the metal tube to correspond to the collimated metal wire through a metal tube clamping unit, so that the collimated metal wire is fed along its axial direction and then inserted into the metal tube; obtaining the relative posture information of the collimated metal wire and the metal tube through a visual feedback unit, and feeding it back to the metal wire clamping unit; electrochemically etching the metal wire segment at the stepped end of the initial microneedle structure through an end processing unit to achieve the molding of the microneedle tip and complete the preparation of the microneedle. The present invention is used to prepare microneedles with stepped ends.

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 tip structures is growing for precise microdevice manipulation. For example, in applications such as flexible electrode implantation for brain-computer interfaces, microneedles with stepped tips enable precise grasping, delivery, and release of flexible microdevices. This places higher demands on the manufacturing precision and reliability of the microneedle tip structure.

[0003] Currently, the two main technologies used to produce microneedles with stepped tips are: focused ion beam processing, which requires specialized equipment and carries high investment and maintenance costs; and femtosecond laser processing, which also suffers from low processing efficiency and high equipment costs. Neither approach meets the requirements for efficient production.

[0004] To address these issues, a microneedle microassembly technology has emerged. This microassembly method has the potential to achieve high-precision microstructures. However, this microassembly technology requires extremely high assembly precision and relies on complex force feedback control systems and high-precision force sensors. This not only increases system complexity but also makes the assembly process cumbersome and time-consuming. Furthermore, even the slightest mistake during the high-precision alignment of the microneedles can cause component damage, reducing production efficiency.

[0005] Although the microassembly process utilizes flexible clamps, achieving precise assembly of stepped end structures still presents numerous challenges. For example, positional deviation during assembly is difficult to effectively control, the clamping force is difficult to precisely control, and workpieces are prone to deformation or damage. Furthermore, there is a lack of targeted automated control strategies. These technical issues make it difficult to ensure the accuracy and consistency of manufactured components, impacting the quality of the final product.

[0006] In summary, the shortcomings of existing technologies in assembly precision control, workpiece protection, and automated control strategies have led to reduced component quality and production efficiency. These issues need to be addressed urgently to meet the demand for efficient production of microneedles with stepped tips. Summary of the Invention

[0007] In order to solve the problem of low efficiency of existing methods for preparing microneedles with stepped ends, 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] The metal wire pretreatment unit is used to stretch the metal wire in a heated state to release internal stress and obtain aligned metal microwires;

[0010] The metal wire clamping unit is used to clamp the aligned metal microwire and dynamically adjust the clamping position of the aligned metal microwire to change the stiffness of the aligned metal microwire. At the same time, based on the relative posture information fed back by the visual feedback unit, the position and stiffness of the aligned metal microwire are adjusted, and the aligned metal microwire is fed along its axial direction so that it is 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 aligned metal microwire, so that the aligned metal microwire is fed along its axial direction and inserted into the metal tube;

[0012] A visual feedback unit is used to obtain the relative posture information of the metal microwire 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 a stepped end of the present invention, the axial direction of the aligned metal microwire 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 perspective relative posture image and the Z-axis perspective relative posture image of the metal microwire and the metal tube after alignment, and obtain the relative posture information of the metal microwire and the metal tube after alignment based on image processing.

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

[0017] Separation state: adjust 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 it along the X-axis direction; make the length L of the metal wire inserted into the metal tube inserted From the initial moment of the current state 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<σs σ→σ at the end time s ;L inserted →0; where σ is the internal stress of the wire, σ s is the highest stress of the wire;

[0019] Low stiffness 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 contact after low stiffness 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;

[0020] High-rigidity contact state: adjust and control the clamping point of the wire clamping unit to the aligned metal microwire, 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 end of the metal tube with low stress; from the initial moment of the current state σ<σ s σ→σ at the end time 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 of σ=0; L inserted >>0;

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

[0023] According to the microneedle preparation system with a stepped end of the present invention, in the separated 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 metal wire clamping unit and the end of the aligned metal microwire; and the elastic deformation of the aligned metal microwire is used to achieve passive compensation for the position error of the end of the aligned metal microwire.

[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 microwire and the end of the aligned metal microwire, 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 metal microwire 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 state transition of the finite state machine includes the distance δ between the end of the aligned metal microwire and the head end of the metal tube. 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 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 after alignment;

[0030] At the end of the low-rigidity stuck state and the high-rigidity stuck state, the flexible hinge clamp releases the aligned metal microwire, 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 feed direction so that the flexible hinge clamp clamps the aligned metal microwire; if θ>θc, or δ e ≠0, it enters the separation state; where θc is the limit horizontal angle at which the metal microwire does not undergo plastic deformation after alignment.

[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 in 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 metal wire pretreatment unit, the heating temperature of the metal wire is 1300-1500°C, and the temperature is controlled by the heating current; the metal 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 drops 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] The present invention has the following beneficial effects: The system, based on the assembly of universal components, produces microneedles with stepped tips without relying on specialized equipment, significantly reducing manufacturing costs. Variable wire stiffness control based on visual feedback effectively simplifies the assembly process and improves assembly success rates. The system utilizes visual guidance for automated assembly control, ensuring the precision and consistency of the resulting microneedle products. This system enables efficient and cost-effective manufacturing of microneedles with stepped tips, laying a solid technical foundation for their widespread application in precision manipulation.

[0037] The microneedles prepared by the system of the present invention can be used for the 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 using the microneedle preparation system with stepped ends of the present invention; the dotted box in the figure represents the stepped structure of the microneedle end;

[0039] Figure 2 Schematic diagram of the metal wire pre-processing unit processing the metal wire; pull Indicates the wire stretching distance, U heat Indicates 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 The schematic diagram of assembling by changing the stiffness of the aligned metal microwires by clamping points; grip The horizontal distance between the clamping point of the metal wire clamping unit on the aligned metal microwire and the head end of the metal tube;

[0041] Figure 4 It is a schematic diagram of the electrochemical etching of 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 5It is a schematic diagram of the microneedle assembly performed by the cooperation of the metal wire clamping unit, the metal tube clamping unit and the visual feedback unit;

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

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

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

[0046] Figure 9 This is a schematic diagram of the high-rigidity contact state between the aligned metal microwire and the metal tube under the control of a finite state machine;

[0047] Figure 10 This is a schematic diagram of the high-rigidity stuck state of the metal microwire and the metal tube after alignment under the control of a finite state machine;

[0048] Figure 11 This is a schematic diagram of the release state of the metal microwire and metal tube after alignment under the control of the finite state machine;

[0049] Figure 12 This 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] Figure 13 This is a schematic diagram of the process of implanting the prepared microneedle-operated flexible nerve electrode into the agar phantom;

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

[0052] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. 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 making any creative efforts shall fall 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 with reference to 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 pre-processing unit 100 is used to stretch the metal wire in a heated state to release internal stress and obtain aligned metal microwires 110; it includes a temperature control circuit and a stress control circuit, 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 microwire 110 and dynamically adjust the clamping position of the collimated metal microwire 110 to change the stiffness of the collimated metal microwire. At the same time, based on the relative posture information fed back by the visual feedback unit 400, the metal wire clamping unit 200 adjusts the position and stiffness of the collimated metal microwire and feeds the collimated metal microwire 110 along its axial direction so that it can 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 metal tube posture to correspond to the aligned metal microwire 110, so that the aligned metal microwire 110 is fed along its axial direction and inserted into the metal tube 310;

[0059] The visual feedback unit 400 is used to obtain the relative posture information of the metal microwire 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 shaping of the microneedle tip and complete the preparation of the microneedle.

[0061] The wire pre-treatment unit 100 utilizes closed-loop stress control, heating and stretching the wire to release internal stress, thereby achieving alignment. The wire clamping unit 200 dynamically adjusts the clamping position to achieve controllable changes in wire stiffness during assembly, and employs a visual feedback system for real-time posture monitoring and compensation control. The terminal processing unit 500 employs electrochemical etching to precisely shape the microneedle tip by monitoring current changes. Electrochemical etching is performed by placing the wire in an electrolyte solution. The etching process is controlled by monitoring changes in the etching current, and etching stops when the etching current reaches a preset level.

[0062] In this embodiment, combined with Figure 5 As shown, the axial direction of the aligned metal microwire 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 metal microwire 110 and the metal tube 310 after alignment, and obtain the relative posture information of the metal microwire 110 and the metal tube 310 after alignment based on image processing.

[0064] The Y-axis camera 410 and the Z-axis camera 420 are arranged 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 Figures 6 to 12 As shown, the wire clamping unit 200 realizes assembly control of the aligned metal microwire 110 and the metal tube 310 based on a finite state machine; the finite state machine performs state transition 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 on the aligned metal microwire 110, so that the clamped aligned metal microwire 110 is aligned with the metal tube 310 along the X-axis direction and fed along the X-axis direction; make the aligned metal microwire 110 inserted into the metal tube 310 by a length L inserted From the initial moment of the current state 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 σ→σ at the end time 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 stiffness 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 stiffness 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 wire clamping unit 200 to the aligned metal microwire 110, and control the 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 can be inserted into the head end of the metal tube 310 with low stress; from the initial moment of the current state σ<σ s σ→σ at the end time 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 realize high stress insertion after high rigidity state alignment; from the initial moment of the current state σ→σ s At the end of σ=0; L inserted >>0;

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

[0072] Figures 6 to 11 As shown in FIG. 4 , it is a schematic diagram of the 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 separated 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 microwire 110; the elastic deformation of the aligned metal microwire 110 is used to passively compensate for the position error of the end of the aligned metal microwire 110;

[0075] In the high-rigidity contact state and the high-rigidity stuck state, that is, 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 microwire 110 and the end of the aligned metal microwire 110, thereby overcoming the insertion resistance and achieving precise assembly.

[0076] Combine 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 metal microwire 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 further, combined Figures 6 to 12 As shown, the control quantity of the finite state machine for state transition 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 δ e =0; its actual judgment is δ e Less than 0.1-0.5 times the diameter of the metal wire, preferably 0.2 times;

[0079] The condition for transitioning from the low-stiffness contact state to the low-stiffness 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 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 aligned metal microwire 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 microwire 110; if θ>θc, or δ e ≠0, the system enters the separation state; where θc is the limit horizontal angle at which the aligned metal microwire 110 does not undergo plastic deformation. After entering the separation state, the flexible hinged gripper again grips the aligned metal microwire, and the linear translation stage 230 moves along the feed direction.

[0083] Going 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 set in 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 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.

[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 release the stress inside 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 can 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 Figure 13 The figure shows the process of microneedle manipulation of a flexible neural electrode. First, an alignment action is performed, placing the microneedle tip within the coaxial cannula 600 and aligning the stepped tip of the microneedle with the manipulation hole of the flexible electrode 700. Next, the manipulation task is performed: the microneedle moves downward within the coaxial cannula 600, with the tip entering the manipulation hole and the stepped portion outside the manipulation hole. This causes the flexible electrode 700 to be peeled off from the substrate 800 and implanted into a brain tissue phantom prepared with 0.6% agar to a specified depth. Finally, a retraction task is performed: the microneedle is retracted, leaving the flexible electrode 700 in the brain tissue phantom. After the microneedle is retracted, the flexible electrode only moves by approximately 32 μm within the brain tissue phantom, which is comparable to the size of a neuron cell. This demonstrates that the microneedle fabricated by the present invention can accurately implant the flexible electrode into a specified location within the brain tissue phantom. Figure 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 illustrative of the principles and applications of the invention. It should be understood that many modifications may be made to the illustrative embodiments, and that other arrangements may be devised, without departing from the spirit and scope of the invention as defined by the appended claims. It should be understood that the various dependent claims and features described herein may be combined in ways other than those described in the original claims. It should also be understood that features described in conjunction with individual embodiments may be used in conjunction with other described embodiments.

Claims

1. A microneedle preparation system with a stepped end, characterized in that: include, A metal wire pre-processing unit (100) is used to stretch the metal wire in a heated state to release internal stress and obtain aligned metal microwires (110); The metal wire clamping unit (200) is used to clamp the collimated metal microwire (110) and dynamically adjust the clamping position of the collimated metal microwire (110) to change the stiffness of the collimated metal microwire; 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 microwire are adjusted, and the collimated metal microwire (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 aligned metal microwire (110), so that the aligned metal microwire (110) is fed along its axial direction and inserted into the metal tube (310); A visual feedback unit (400) is used to obtain relative posture information of the aligned metal microwire (110) and the metal tube (310), 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 formation of the microneedle tip and complete the preparation of the microneedle; The axial direction of the aligned metal microwire (110) is taken as the X-axis direction; The visual feedback unit (400) includes a Y-axis camera (410) and a Z-axis camera (420), which are used to respectively obtain a Y-axis perspective relative posture image and a Z-axis perspective relative posture image of the collimated metal microwire (110) and the metal tube (310), and obtain relative posture information of the collimated metal microwire (110) and the metal tube (310) based on image processing; The metal wire clamping unit (200) realizes assembly control of the aligned metal microwire (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: Separation state: adjusting and controlling the metal wire clamping unit (200) to clamp the aligned metal microwire (110), so that the clamped aligned metal microwire (110) is aligned with the metal tube (310) along the X-axis direction, and feeding along the X-axis direction; The length L of the aligned metal microwire (110) inserted into the metal tube (310) inserted From the initial moment of the current state L inserted =0 to the end time L inserted →0; Low-rigidity contact state: controlling the metal wire clamping unit (200) to continue feeding along the X-axis direction; making the end of the metal microwire (110) and the head end of the metal tube (310) realize low-stress contact after alignment in the low-rigidity state; from the initial moment of the current state σ<σ s σ→σ at the end time s ;L inserted →0; where σ is the internal stress of the wire, σ s is the highest 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) 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; High-rigidity contact state: adjusting and controlling the metal wire clamping unit (200) to the clamping point of the aligned metal microwire (110), and controlling 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) are inserted with low stress; from the initial moment of the current state σ<σ s σ→σ at the end time 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 of the metal tube (310) after alignment in the high-rigidity state; from the initial moment of the current state σ→σ s At the end of σ=0; L inserted >>0; Release state: controlling the metal wire clamping unit (200) to release the aligned metal microwire (110), σ=0.

2. The microneedle preparation system with stepped ends according to claim 1, characterized in that: 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) on the aligned metal microwire (110) and the end of the aligned metal microwire (110); and the elastic deformation of the aligned metal microwire (110) is utilized to passively compensate for the position error of the end of the aligned metal microwire (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 microwire (110) and the end of the aligned metal microwire (110), thereby overcoming the insertion resistance.

3. The microneedle preparation system with stepped ends according to claim 2, 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 aligned metal microwire (110) via 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.

4. The microneedle preparation system with stepped ends according to claim 3, characterized in that: The control quantity of the state transfer of the finite state machine 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 visible length per unit time The variation 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 aligned metal microwire (110), and the linear displacement stage (230) moves in the opposite direction of the feeding direction to enter the release 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 aligned metal microwire (110); if θ>θc, or δ e ≠0, it enters the separation state; where θc is the limit horizontal angle at which the metal microwire (110) does not undergo plastic deformation after alignment.

5. 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 metal tube (310) is axially aligned along the X axis.

6. 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.

7. 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 drops from 80-90% of the initial value to 10-20%, the power supply is cut off.

8. 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.

Images