Hollow metal microneedle with curvature, preparation method of hollow metal microneedle and microneedle injection device for ophthalmologic operation

Abstract

The invention provides a hollow metal microneedle with curvature, a preparation method of the hollow metal microneedle and a microneedle injection device for ophthalmologic operation, and relates to the technical field of medical instruments. The preparation method of the hollow metal microneedle with the curvature comprises the following steps: firstly, carrying out reverse stretching photoetching treatment on a photoresist material by utilizing a blunt injection needle to obtain a linear solid micro-mold; then forming a curvature on the linear solid micro-mold through an air flow forming method to obtain a solid micro-mold with the curvature; and forming a metal coating outer wall through metal electroplating, and then removing the photoresist to obtain the hollow metal microneedle with curvature. According to the preparation method of the hollow metal microneedle, photoetching and airflow forming methods are combined, and the preparation method has the technical advantages of being simple in machining process, high in yield and suitable for industrial production; meanwhile, the hollow metal microneedle is of an arched structure with curvature and can fully adapt to injection under the retina, and shearing force of an operation on eye tissue is reduced.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical devices, in particular to a hollow metal microneedle with curvature, a preparation method thereof and a microneedle injection device for ophthalmic surgery. BACKGROUND

[0002] In the field of ophthalmology, especially in the treatment of retinal diseases, the subretinal space has become a crucial target area for drug delivery. When treating diseases such as age-related macular degeneration (AMD), retinitis pigmentosa (RP), etc., it is often necessary to precisely deliver gene therapy vectors, stem cell suspensions or other biological agents to the subretinal space between the retinal pigment epithelium (RPE) layer and the photoreceptor cells. Traditional delivery methods, such as transscleral injection or vitrectomy combined with subretinal injection, are effective, but they are all highly invasive surgical procedures. These operations require very high skills from the operator, and there is a risk of damaging the choroid, causing hemorrhage, causing iatrogenic retinal breaks, etc. The trauma of the surgery itself can also trigger inflammatory and fibrotic reactions, affecting the final treatment outcome.

[0003] To reduce the invasiveness of surgery, microneedle technology has been introduced into the field of ophthalmology as a new minimally invasive drug delivery method. However, existing microneedle structures often do not have curvature, causing significant damage to the ocular tissues during surgery. At the same time, the production efficiency of existing hollow microneedles for ophthalmic use is low, and the structural precision or consistency is insufficient.

[0004] In view of the above, the present application is proposed. SUMMARY

[0005] The first object of the present application is to provide a preparation method of a hollow metal microneedle with curvature, which has the technical advantages of simple processing technology, high yield, and suitability for industrial production. At the same time, the hollow metal microneedle prepared has an arch-shaped structure with curvature, which can fully adapt to the injection optimization of the subretinal space and reduce the shear force on the surgical tissues.

[0006] The second object of the present application is to provide a hollow metal microneedle with curvature.

[0007] The third object of the present application is to provide a microneedle injection device for ophthalmic surgery.

[0008] In order to achieve the above objects of the present application, the following technical solutions are adopted: The present application provides a preparation method of a hollow metal microneedle with curvature, which comprises: (A) using a blunt-ended injection needle to perform reverse tensile photolithography on a photoresist material to obtain a linear solid micromold; (B) placing the linear solid micromould into an air flow forming device, forming curvature on the linear solid micromould by air flow forming method, obtaining a solid micromould with curvature; (C) performing metal electroplating on the surface of the solid micromould with curvature, forming a metal plating layer; then removing the solid micromould formed by the photoresist, obtaining a hollow metal microneedle with curvature; The hollow metal microneedle with curvature is arranged on the injection needle body.

[0009] Further, the photoresist material in step (A) comprises at least one of TMMR S20002, SINR-10003, SU-82050 and Intervia 8000, and is preferably SU-82050.

[0010] Further, the reverse tensile photoetching in step (A) comprises the following steps: The photoresist material is coated on the wafer using a spin coater, heated to 150°C, and after 10 minutes of heat preservation, the temperature is lowered to 75-85°C, to obtain a to-be-processed photoresist material; then a blunt injection needle is used to vertically stretch the to-be-processed photoresist material at a temperature of 75-85°C at a speed of 1mm / s, to obtain a linear solid micromould; Preferably, the reverse tensile photoetching is performed in a wire drawing machine; Preferably, the outer diameter of the blunt injection needle is 25G-27G.

[0011] Further, the length of the linear solid micromould is 5-10mm.

[0012] Further, the air flow forming wind speed in step (B) is 0.1-5.8m / s; Further, the air flow forming wind speed in step (B) is 3.2-5.8m / s; Preferably, the air flow forming time is 5-15min.

[0013] Further, the air flow forming wind speed in step (B) is positively correlated with the curvature of the solid micromould; When the length of the linear solid micromould is 5mm, the air flow forming wind speed is 3.2m / s, and the air flow forming time is 10min, the curvature of the solid micromould is 0.05-0.1; When the length of the linear solid micromould is 5mm, the air flow forming wind speed is 4.7m / s, and the air flow forming time is 10min, the curvature of the solid micromould is 0.1-0.2; When the length of the linear solid micro-mold is 5mm, the air flow forming wind speed is 5.8m / s, and the air flow forming time is 10min, the curvature of the solid micro-mold is 0.3-0.35; When the length of the linear solid micro-mold is 10mm, the air flow forming wind speed is 3.2m / s, and the air flow forming time is 10min, the curvature of the solid micro-mold is 0.1-0.15; When the length of the linear solid micro-mold is 10mm, the air flow forming wind speed is 4.7m / s, and the air flow forming time is 10min, the curvature of the solid micro-mold is 0.2-0.3; When the length of the linear solid micro-mold is 10mm, the air flow forming wind speed is 5.8m / s, and the air flow forming time is 10min, the curvature of the solid micro-mold is 0.48-0.52; Further, the electroplating material of the metal electroplating in the step (C) comprises at least one of nickel, chromium and gold, and preferably is nickel.

[0014] Preferably, the thickness of the metal plating layer in the step (C) is 0.5-5 µm.

[0015] Further, the preparation method further comprises: (D) grinding and polishing the hollow metal microneedle with curvature to prepare a hollow beveled tip. Preferably, the bevel angle of the hollow beveled tip is 40-50u.

[0016] The hollow metal microneedle with curvature prepared by the above preparation method.

[0017] The hollow metal microneedle with curvature provided by the application is used in the preparation of a microneedle injection device for ophthalmology.

[0018] The microneedle injection device for ophthalmic surgery provided by the application comprises the hollow metal microneedle with curvature, a needle seat and a syringe. The hollow metal microneedle with curvature is a needle body, one end of the needle body is provided with a hollow metal microneedle structure with curvature, and the other end is riveted and connected with the needle seat; the needle seat and the syringe are connected by a luer screw structure.

[0019] Compared with the prior art, the application has the following beneficial effects: The application provides a preparation method of the hollow metal microneedle with curvature, which comprises the following steps: firstly, a linear solid micromold is obtained by inversely stretching a photoresist material through a blunt injection needle and photoetching; then, a solid micromold with curvature is obtained by forming the curvature on the linear solid micromold through an air flow forming method; and finally, the photoresist is removed after a metal plating layer is formed through metal electroplating, so that the hollow metal microneedle with curvature is obtained. The preparation method of the hollow metal microneedle has the technical advantages of simple processing technology, high product yield and suitability for industrial production by combining the photoetching and the air flow forming method. Meanwhile, the air flow physical forming method avoids the risk of thermal deformation of the microneedle. The hollow metal wall is formed through the electroplating process. Since the electroplating is carried out in the circulating and filtered electroplating solution, the metal layer of the hollow metal microneedle is ensured to be uniform and dense. In addition, the hollow metal microneedle prepared by the application has an arch-shaped structure with curvature, which can fully adapt to the injection optimization under the retina and reduce the shear force on the surgical tissue.

[0020] The hollow metal microneedle with curvature has the technical advantages of good curvature consistency, high structural precision and high surface smoothness, and can be widely applied to the preparation process of the microneedle injection device for ophthalmology. BRIEF DESCRIPTION OF DRAWINGS

[0021] In order to more clearly illustrate the specific embodiments of the application or the technical solutions in the prior art, the following will briefly introduce the drawings needed to be used in the description of the specific embodiments or the prior art. Obviously, the drawings in the following description are some embodiments of the application, and other drawings can also be obtained by those skilled in the art without creative labor.

[0022] Figure 1 A connection mode diagram of an injection needle body and an injection needle seat of an existing microneedle injection device for ophthalmic surgery; Figure 2 A connection mode diagram of an injection needle body and an injection needle seat of the microneedle injection device for ophthalmic surgery of the application; Figure 3 A structure schematic diagram of an injection needle body and an injection needle seat of the microneedle injection device for ophthalmic surgery of the application; Figure 4 A structure schematic diagram of an existing microneedle injection device for ophthalmic surgery before assembly; Figure 5 A structure schematic diagram of an existing microneedle injection device for ophthalmic surgery after assembly; Figure 6 A structure schematic diagram of the microneedle injection device for ophthalmic surgery of the application before assembly; Figure 7 A structure schematic diagram of the microneedle injection device for ophthalmic surgery of the application after assembly; Figure 8 Figure 1 is a schematic diagram of the hollow metal microneedle tip of the micro-needle injection device for ophthalmic surgery of the present application in concentric alignment with the injection needle body and the injection needle seat through the hollow channel. Figure 9 Figure 2 is a schematic diagram of the preparation process of the hollow metal microneedle with curvature provided in Embodiment 1 of the present application. Figure 10 Figure 3 is a solid micro-mold with curvature obtained by air flow forming provided in Embodiments 1-3 of the present application. Figure 11 Figure 4 is a graph of the relationship between the air flow forming wind speed and the curvature of the solid micro-mold provided in the present application.

[0023] Figure 1 is a schematic diagram of the hollow metal microneedle tip of the micro-needle injection device for ophthalmic surgery of the present application in concentric alignment with the injection needle body and the injection needle seat through the hollow channel. DETAILED DESCRIPTION

[0024] The technical solutions of the present application will be described below in conjunction with the embodiments, obviously, the described embodiments are part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0025] According to an aspect of the present application, a preparation method of a hollow metal microneedle with curvature, the preparation method comprises: (A) performing reverse tensile lithography on photoresist material using a blunt injection needle to obtain a linear solid micro-mold; (B) placing the linear solid micro-mold in an air flow forming device to form curvature on the linear solid micro-mold by air flow forming method to obtain a solid micro-mold with curvature; (C) performing metal electroplating on the surface of the solid micro-mold with curvature to form a metal plating layer; then removing the solid micro-mold formed by photoresist to obtain a hollow metal microneedle with curvature; The hollow metal microneedle with curvature is arranged on the injection needle body 1.

[0026] The application provides a preparation method of the hollow metal microneedle with curvature, which comprises the following steps: firstly, reverse tensile photoetching is performed on a photoresist material by using a blunt injection needle, so that a linear solid micromold is obtained; then, curvature is formed on the linear solid micromold by using an air flow forming method, so that a solid micromold with curvature is obtained; then, a metal plating layer is formed by metal electroplating, and the photoresist is removed, so that the hollow metal microneedle with curvature is obtained. The preparation method of the hollow metal microneedle has the technical advantages of simple processing technology, high product yield and suitability for industrial production by combining the photoetching and the air flow forming method. Meanwhile, the air flow physical forming method can avoid the risk of thermal deformation of the microneedle. The hollow metal wall is formed by the electroplating process. Since the electroplating is performed in a circulating and filtered electroplating solution, the metal layer of the hollow metal microneedle can be ensured to be uniform and dense. In addition, the hollow metal microneedle prepared by the application has an arched structure with curvature, which can fully adapt to the injection optimization under the retina and reduce the shearing force on the surgical tissue.

[0027] In a preferred embodiment of the application, the photoresist material in step (A) comprises at least one of TMMR S20002, SINR-10003, SU-82050 and Intervia 8000, and preferably is SU-82050.

[0028] In a preferred embodiment of the application, the reverse tensile photoetching in step (A) comprises the following steps: the photoresist material is coated on a wafer by using a spin coater, the temperature is raised to 150 DEG C, the temperature is kept for 10 min, and then the temperature is lowered to 75-85 DEG C, so that the photoresist material to be treated is obtained; then, the photoresist material to be treated is vertically stretched at a speed of 1 mm / s in the temperature range of 75-85 DEG C by using a blunt injection needle, so that the linear solid micromold is obtained. Preferably, the reverse tensile photoetching comprises the following steps: the photoresist material is coated on a 6-inch wafer by using a spin coater at a speed of 1000 rpm, the thickness is 160 mm, the temperature is raised to 150 DEG C, the temperature is kept for 10 min, and then the temperature is lowered to 75-85 DEG C, so that the photoresist material to be treated is obtained; then, the photoresist material to be treated is vertically stretched at a speed of 1 mm / s in the temperature range of 75-85 DEG C by using a blunt injection needle, so that the linear solid micromold is obtained. Preferably, the reverse tensile photoetching is performed in a wire drawing machine. Preferably, the outer diameter of the blunt injection needle is 25G-27G.

[0029] In a preferred embodiment of the application, the length of the linear solid micromold is 5-10 mm, and preferably is 5 mm or 10 mm.

[0030] As an optional embodiment, the length of the linear solid micro-mold is 5-10 mm, for example, can be 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, or any value between 5-10 mm; In a preferred embodiment of the present application, the wind speed of the air flow forming in step (B) is 0.1-5.8 m / s; As an optional embodiment, the wind speed of the air flow forming is 0.1-5.8 m / s, for example, can be 0.1-5.8 m / s, 1.5 m / s, 3.2 m / s, 4.7 m / s, 5.0 m / s, 5.8 m / s, or any value between 0.1-5.8 m / s; Preferably, the wind speed of the air flow forming in step (B) is 3.2-5.8 m / s; In a preferred embodiment of the present application, the time of the air flow forming is 5-15 min, preferably 10 min.

[0031] As an optional embodiment, the time of the air flow forming is 5-15 min, for example, can be 5 min, 6 min, 7 min, 8 min, 9 min, 10 min, 11 min, 12 min, 13 min, 14 min, 15 min, or any value between 5-15 min; In a preferred embodiment of the present application, the wind speed of the air flow forming in step (B) is positively correlated with the curvature of the solid micro-mold; As a preferred embodiment, the present application is verified by experiment, when the length of the linear solid micro-mold is 5 mm, the wind speed of the air flow forming is 3.2 m / s, and the time of the air flow forming is 10 min, the curvature of the solid micro-mold is 0.05-0.1; When the length of the linear solid micro-mold is 5 mm, the wind speed of the air flow forming is 4.7 m / s, and the time of the air flow forming is 10 min, the curvature of the solid micro-mold is 0.1-0.2; When the length of the linear solid micro-mold is 5 mm, the wind speed of the air flow forming is 5.8 m / s, and the time of the air flow forming is 10 min, the curvature of the solid micro-mold is 0.3-0.35; When the length of the linear solid micro-mold is 10 mm, the wind speed of the air flow forming is 3.2 m / s, and the time of the air flow forming is 10 min, the curvature of the solid micro-mold is 0.1-0.15; When the length of the linear solid micro-mold is 10 mm, the wind speed of the air flow forming is 4.7 m / s, and the time of the air flow forming is 10 min, the curvature of the solid micro-mold is 0.2-0.3; When the length of the linear solid micro-mold is 10 mm, the air flow forming wind speed is 5.8 m / s, and the air flow forming time is 10 min, the curvature of the solid micro-mold is 0.48-0.52.

[0032] Therefore, the hollow micro-needle mold with fixed curvature is obtained by controlling the length of the linear solid micro-mold, the air flow forming wind speed, and the forming time. It is verified that the micro-needle mold structure has good consistency, high production efficiency, low defectiveness, and is suitable for large-scale industrial production.

[0033] In a preferred embodiment of the present application, the plating material of the metal plating in step (C) comprises at least one of nickel, chromium and gold, preferably nickel.

[0034] In the above preferred embodiment, the thickness of the metal plating layer in step (C) is 0.5-5 µm.

[0035] In a preferred embodiment of the present application, the preparation method further comprises: (D) grinding and polishing the hollow metal micro-needle with curvature to prepare a hollow beveled tip; In the above preferred embodiment, the beveled angle of the hollow beveled tip is 40-50u.

[0036] According to one aspect of the present application, the hollow metal micro-needle with curvature prepared by the above preparation method.

[0037] The hollow metal micro-needle with curvature provided by the present application has the technical advantages of good curvature consistency, high structural precision and high surface smoothness.

[0038] According to one aspect of the present application, the present application provides a micro-needle injection device for ophthalmic surgery, which comprises an injection needle body 1, an injection needle seat 2 and an injector 3. Wherein: one end of the injection needle body 1 is provided with the hollow metal micro-needle structure 11 with curvature, and the other end is riveted and connected with the needle seat; the needle seat is connected with the injector 3 in a luer screw structure.

[0039] The application provides a microneedle injection device for ophthalmic surgery, and the injection needle body 1 and the injection needle seat 2 are connected in a riveting mode, that is, the needle body is pressed into the injection needle seat 2 by pressure to realize mechanical connection. The inner flat joint is adopted for the connection between the inner cavity 21 of the needle seat and the needle body, and the cavity for connecting the syringe 3 and the needle body is reduced on the basis of the original inner conical joint standard. Meanwhile, the connection between the injection needle seat 2 and the syringe 3 adopts a luer spiral structure connection, which is suitable for the connection of multiple syringes 3. In addition, the microneedle injection device for ophthalmic surgery is concentrically aligned (see the drawing) through the hollow hole between the terminal needle tip, the needle body and the injection needle seat 2 in the overall processing, and accurate eyeball injection can be realized.

[0040] Figure 1 It is a connection mode diagram of the injection needle body 1 and the injection needle seat 2 of the existing microneedle injection device for ophthalmic surgery.

[0041] Figure 2 It is a connection mode diagram of the injection needle body 1 and the injection needle seat 2 of the microneedle injection device for ophthalmic surgery.

[0042] Figure 3 It is a structure schematic diagram of the injection needle body 1 and the injection needle seat 2 of the microneedle injection device for ophthalmic surgery.

[0043] Figure 4 It is a structure schematic diagram of the existing microneedle injection device for ophthalmic surgery before assembly. Among them: Figure 4 (A) is a direct view structure diagram of the existing microneedle injection device for ophthalmic surgery before assembly; Figure 4 (B) is a sectional view structure diagram of the existing microneedle injection device for ophthalmic surgery before assembly; Figure 5 It is a structure schematic diagram of the existing microneedle injection device for ophthalmic surgery after assembly. Among them: Figure 5 (A) is a direct view structure diagram of the existing microneedle injection device for ophthalmic surgery after assembly; Figure 5 (B) is a sectional view structure diagram of the existing microneedle injection device for ophthalmic surgery after assembly; Figure 6 It is a structure schematic diagram of the microneedle injection device for ophthalmic surgery before assembly. Among them: Figure 6 (A) is a direct view structure diagram of the microneedle injection device for ophthalmic surgery before assembly; Figure 6 (B) is a sectional view structure diagram of the microneedle injection device for ophthalmic surgery before assembly; Figure 7 It is a structure schematic diagram of the microneedle injection device for ophthalmic surgery after assembly. Among them: Figure 7 (A) is a direct view structure diagram of the microneedle injection device for ophthalmic surgery after assembly; Figure 7Figure 3 is a sectional view of the micro-needle injection device for ophthalmic surgery of the present application after assembly; It should be noted that when the existing micro-needle device adopts the inner conical joint structure, the linking head of the syringe 3 will have a cavity after assembly with the micro-needle device of this structure, and a large amount of drug liquid will be left on the inner cavity wall during the injection of the syringe 3, resulting in drug liquid loss and high cost. For details, see Figure 1 .

[0044] Therefore, referring to Figure 2 、 3 , the connection between the injection needle body 1 and the injection needle seat 2 of the injection device of the present application is achieved by pressing the needle body into the injection needle seat 2 through pressure in the form of riveting, realizing mechanical connection. The connecting head 22 of the inner cavity 21 of the needle seat and the needle body adopts an inner flat joint, which reduces the cavity of the syringe 3 and the needle body connection based on the original inner conical joint standard.

[0045] It should also be noted that the base in the existing micro-needle device is generally flat, and when connected with a flat syringe 3, there is a possibility of flying needle due to the flat connection of the two connection sections. When connected with a spiral syringe 3, the cavity of the base increases due to the incomplete fit with the spiral structure of the syringe 3, resulting in increased drug liquid loss.

[0046] Therefore, referring to Figure 3 , the connection between the injection needle seat 2 and the syringe 3 of the present application adopts a Luer spiral structure connection, which not only adapts to the connection of multiple syringes 3, but also completely fits and tightens when connected with flat syringes 3 and screw syringes 3, preventing flying needles and avoiding the increase in the cavity of the base due to incomplete fit, which in turn causes increased drug liquid loss.

[0047] For details of the comparison between the micro-needle injection device for ophthalmic surgery of the present application before and after assembly and the existing micro-needle injection device for ophthalmic surgery, see Figures 4-7 .

[0048] Figure 8 Figure 4 is a structural schematic diagram of the hollow metal micro-needle tip of the micro-needle injection device for ophthalmic surgery of the present application being concentrically aligned with the injection needle body 1 and the injection needle seat 2 through the hollow hole; As can be seen from Figure 8 , the hollow metal micro-needle tip of the present application is concentrically aligned with the injection needle body 1 and the injection needle seat 2 through the hollow hole, which can achieve precise eye part injection; In a preferred embodiment of the present application, the end angle of the hollow metal micro-needle structure 11 with curvature on the injection needle body 1 is formed by laser cutting process to form a 0°~85° chamfer design, which can complete the injection while minimizing the damage to the eye tissue.

[0049] The technical solutions of the present application will be further described below in combination with embodiments.

[0050] Embodiment 1 Figure 9 A schematic diagram of the preparation process of the hollow metal microneedle with curvature for the present embodiment.

[0051] Referring to Figure 9 A method for preparing a hollow metal microneedle with curvature, the preparation method comprising: A, reverse photoetching: A 27G injection needle is used as an injection needle body 1 to vertically stretch a SU-8 2050 viscoelastic material, and the wire drawing machine is equipped with a wire drawing component and a heating component; wherein: The drawing component is located at the top of the drawing machine, allowing vertical drawing movement, so as to manufacture a micromechanical mold with the viscoelastic material; the heating component is composed of a circular metal plate for adjusting the temperature.

[0052] Before stretching the solid micro-mold, a 27G injection needle with a length of 1.5 inches and an outer diameter of 300 mm is adjusted on the stretching system, and a photoresist (SU-82050) is coated on a 6-inch wafer using a spin coater at a speed of 1000 rpm, with a thickness of 160 mm. The temperature is raised to 150°C, and the SU-82050 is solidified at room temperature; vertical stretching is performed at a temperature range of 75-85°C at a speed of 1 mm / s, to obtain a linear solid micro-mold (SU-8 mold); The linear solid micro-mold has a diameter of 40µm and a length of 5mm.

[0053] B, forming a curve: The linear solid micro-mold is held vertically downward on the wire drawing machine, and a controlled airflow is used to perform airflow forming treatment on the linear solid micro-mold to form a curve to obtain a solid micro-mold with curvature; The airflow forming wind speed (controllable airflow rate) is 3.2m / s, lasting for 10 minutes, and the temperature is controlled at 75-85°C, and the airflow forming wind speed is adjusted by the vertical wind generated by the centrifugal fan.

[0054] C, nickel plating and electroplating: A layer of nickel seed layer is plated on the surface of the solid micro-mold with curvature (arch-shaped micro-injector solid mold) using an electroplating machine for nickel electroplating. The specific method is: 10mA / mm 2 The current density is maintained for 2 hours to obtain a nickel wall thickness of 30µm, forming an arch-shaped micro-injector outer diameter.

[0055] D, bevel tip polishing: The pointed bevel angle is modified using a polishing system, specifically: the polishing system is composed of an 8 amp motor and a rubber bumper connected to a piece of scotchstone. The electroplated arcuate micro-jet is placed in a tilting system that holds each arcuate micro-jet at a fixed angle. Polishing is accomplished by aligning each arcuate micro-jet to the scotchstone and rotating the motor at 100 rpm. The resulting arcuate micro-jet has an inner surface curve; The bevel angle of the polished hollow bevel tip is 45u.

[0056] E. Remove the SU-8 mold and clean up: Remove the solid micro-mold of the arcuate micro-jet using SU-8 remover for 1 hour to produce a hollow metal microneedle with curvature.

[0057] After testing, the specific size of the hollow metal microneedle (arcuate micro-jet) with curvature prepared in this embodiment is: length 5mm, inner diameter 40mm, outer diameter 100mm, bevel angle about 45u, and microneedle curvature 0.05~0.1.

[0058] It should be noted that the above step (E) of removing the SU-8 mold and cleaning up is specifically as follows: 1. Sample fixation and cavity preparation: Fix the sample on the etching tray with high-temperature-resistant tape (polyimide material) (to avoid displacement of the sample under vacuum), ensure that the adhesive layer is upward and not blocked; open the plasma etching machine and vacuum to 5~10 mTorr (1 Torr = 133.3 Pa) in the cavity to exclude air interference.

[0059] 2. Gas proportioning and parameter setting: Introduce O2 and CF4 gas, and control the flow ratio of O2:CF4=9:1 (volume ratio) (CF4 excess will corrode the silicon substrate, which needs to be strictly controlled); Set the radio frequency power to 100~300W, the etching pressure to 20~50mTorr, and calculate the etching time according to the thickness of the adhesive layer (the etching rate is about 2~5μm / min, and 20% redundancy time is needed to avoid residue). For example: 100μm thick SU-8, etching time =100μm÷3μm / min×1.2≈40 minutes.

[0060] 3. Subsection etching and real-time monitoring: Use the "subsection etching" mode (pause every 10 minutes), open the cavity observation window to check the residual adhesive layer (the substrate will present the original color after complete removal, such as bright gray for silicon wafer); if carbon residue is found at the bottom of the high aspect ratio structure, O2 can be introduced alone (flow rate 50sccm) for 5~10 minutes of low-power (100W) etching to oxidize the residual carbon.

[0061] 4. Post processing and cleaning: After etching, the vacuum is broken by introducing nitrogen gas (pressure rises to atmospheric pressure) and the sample is removed. The sample surface is wiped with IPA to remove possible polymer deposits (plasma etching can produce traces of carbon powder) and dried with nitrogen.

[0062] Example 2 This example is the same as example 1 except that in step B, the air flow forming wind speed (controllable air flow rate) is 4.7 m / s.

[0063] After testing, the hollow metal microneedle (arch-shaped microinjector) with curvature prepared in this example has the following specific dimensions: length of 5 mm, inner diameter of 40 mm, outer diameter of 100 mm, oblique sharp angle of about 45u, and microneedle curvature of 0.1-0.2.

[0064] Example 3 This example is the same as example 1 except that in step B, the air flow forming wind speed (controllable air flow rate) is 5.8 m / s.

[0065] After testing, the hollow metal microneedle (arch-shaped microinjector) with curvature prepared in this example has the following specific dimensions: length of 5 mm, inner diameter of 40 mm, outer diameter of 100 mm, oblique sharp angle of about 45u, and microneedle curvature of 0.3-0.35.

[0066] Figure 10 The solid micro-mold with curvature obtained by air flow forming in examples 1-3 provided in this application is shown in the following figure.

[0067] Wherein: Figure 10 The hollow blank group is a control implementation when the air flow forming wind speed is 0 m / s.

[0068] Example 4 This example is the same as example 1 except that in step A, the length of the linear solid micro-mold is 10 mm.

[0069] After testing, the hollow metal microneedle (arch-shaped microinjector) with curvature prepared in this example has the following specific dimensions: length of 10 mm, inner diameter of 40 mm, outer diameter of 100 mm, oblique sharp angle of about 45u, and microneedle curvature of 0.1-0.15.

[0070] Example 5 This example is the same as example 2 except that in step A, the length of the linear solid micro-mold is 10 mm.

[0071] The hollow metal microneedle (arch-shaped microejector) prepared in the embodiment has the following specific dimensions: length of 10 mm, inner diameter of 40 mm, outer diameter of 100 mm, oblique tip angle of about 45 u, and microneedle curvature of 0.2-0.3.

[0072] Example 6 In the embodiment, the length of the linear solid micromold in step A is 10 mm, and the rest is the same as in Example 3.

[0073] The hollow metal microneedle (arch-shaped microejector) prepared in the embodiment has the following specific dimensions: length of 10 mm, inner diameter of 40 mm, outer diameter of 100 mm, oblique tip angle of about 45 u, and microneedle curvature of 0.48-0.52.

[0074] Figure 11 The airflow forming wind speed and the curvature of the solid micromold are provided in the application.

[0075] Referring to Figure 11 , Figure 11 R is the radius of curvature, and the curvature (k) of the hollow metal microneedle is defined as: ; Where: R is the radius of curvature, the curve of the hollow metal microneedle is fitted to an arbitrary circle, and the radius of curvature is measured. A segment (arc) of the circle is taken as the reference point for taking the radius, as shown in Figure 11 The curvature of each curve is calculated using computer-based imaging software using images captured using a bright-field microscope.

[0076] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present application, and not to limit them; although the present application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the foregoing embodiments, or make equivalent substitutions for part or all of the technical features; and these modifications or substitutions do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present application.

Claims

1. A method for preparing a hollow metal microneedle with curvature, characterized in that, The preparation method includes: (A) A linear solid micromold is obtained by reverse stretching photolithography of photoresist material using blunt-tip injection molding. (B) A linear solid micromold is placed in an airflow forming device, and curvature is formed on the linear solid micromold by airflow forming to obtain a solid micromold with curvature; (C) Metal electroplating is performed on the surface of a solid micromold with curvature to form a metal coating; then the solid micromold formed by photoresist is removed to obtain a hollow metal microneedle with curvature. The curved hollow metal microneedle is disposed on the injection needle body of the blunt-tipped injection needle.

2. The method for preparing a hollow metal microneedle with curvature according to claim 1, characterized in that, The photoresist material in step (A) includes at least one of TMMR S20002, SINR-10003, SU-82050 and Intervia 8000.

3. The method for preparing a hollow metal microneedle with curvature according to claim 1, characterized in that, The reverse stretching lithography in step (A) includes the following steps: Photoresist material is coated onto a wafer using a spin coater, heated to 150°C, held for 10 minutes, and then cooled to 75-85°C to obtain the photoresist material to be processed. Subsequently, the photoresist material to be processed is vertically stretched at a speed of 1 mm / s within a temperature range of 75-85°C using a blunt-tipped injection needle to obtain a linear solid micromold. And / or, the reverse stretching lithography is performed in a wire drawing machine; And / or, the outer diameter of the blunt-tipped injection needle is 25G~27G.

4. The method for preparing a hollow metal microneedle with curvature according to claim 3, characterized in that, The length of the linear solid micromold is 5~10mm.

5. The method for preparing a hollow metal microneedle with curvature according to claim 1, characterized in that, The wind speed for airflow shaping in step (B) is 0.1~5.8 m / s; And / or, the wind speed for airflow shaping in step (B) is 3.2~5.8m / s; And / or, the airflow shaping time is 5~15 min.

6. The method for preparing a hollow metal microneedle with curvature according to claim 1, characterized in that, In step (B), the airflow velocity for airflow shaping is positively correlated with the curvature of the solid micro-mold; When the length of the linear solid micromold is 5 mm, the air velocity for airflow forming is 3.2 m / s, and the airflow forming time is 10 min, the curvature of the solid micromold is 0.05~0.

1. When the length of the linear solid micromold is 5 mm, the air velocity for airflow forming is 4.7 m / s, and the airflow forming time is 10 min, the curvature of the solid micromold is 0.1~0.

2. When the length of the linear solid micromold is 5 mm, the air velocity for airflow forming is 5.8 m / s, and the airflow forming time is 10 min, the curvature of the solid micromold is 0.3~0.

35. When the length of the linear solid micromold is 10 mm, the air velocity for airflow forming is 3.2 m / s, and the airflow forming time is 10 min, the curvature of the solid micromold is 0.1~0.

15. When the length of the linear solid micromold is 10 mm, the air velocity for airflow forming is 4.7 m / s, and the airflow forming time is 10 min, the curvature of the solid micromold is 0.2~0.

3. When the length of the linear solid micromold is 10 mm, the air velocity for airflow molding is 5.8 m / s, and the airflow molding time is 10 min, the curvature of the solid micromold is 0.48~0.

52.

7. The method for preparing a hollow metal microneedle with curvature according to claim 1, characterized in that, The electroplating material used in step (C) includes at least one of nickel, chromium, and gold; And / or, the thickness of the metal coating in step (C) is 0.5~5 µm.

8. The method for preparing a hollow metal microneedle with curvature according to claim 1, characterized in that, The preparation method further includes: (D) The step of grinding and polishing hollow metal microneedles with curvature to prepare hollow oblique tips; And / or, the angle of the hollow bevel is 40~50°.

9. The hollow metal microneedles with curvature prepared by the method of any one of claims 1 to 8.

10. A microneedle injection device for ophthalmic surgery, characterized in that, The ophthalmic surgical microneedle injection device comprises: a hollow metal microneedle with curvature as described in claim 9, an injection needle holder, and a syringe; Wherein: the hollow metal microneedle with curvature as described in claim 9 is an injection needle body, one end of the injection needle body is provided with a hollow metal microneedle structure with curvature, and the other end is riveted to the injection needle seat; the injection needle seat and the syringe are connected by a Luer spiral structure.

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