CN114588527A - Silicon-based ice microneedle and preparation method thereof - Google Patents

Abstract

The invention discloses a silicon-based ice microneedle and a preparation method thereof, wherein the silicon-based ice microneedle comprises a silicon wafer and a plurality of micron needle-shaped structures which are formed on the silicon wafer and distributed in an array manner, hollow structures penetrating through the tops of the micron needle-shaped structures to the bottom of the silicon wafer are formed in the micron needle-shaped structures and the silicon wafer, and an ice soluble needle point is formed in the hollow structures. The substrate of the invention adopts the hollow silicon-based microneedle, the preparation process is simple, the cost is lower, and the invention is suitable for large-scale industrial production; an ice soluble needle point is formed in the hollow silicon-based microneedle, so that the administration step is simplified, and the drug-loading capacity is improved; the silicon-based ice microneedle improves the mechanical properties of the original hollow silicon-based microneedle and the original soluble microneedle, and solves the problems that the microneedle is easy to break and is difficult to penetrate the skin in the prior art.

Description

Silicon-based ice microneedle and preparation method thereof

Technical Field

The invention belongs to the technical field of silicon-based microneedles, and particularly relates to a silicon-based microneedle and a preparation method thereof.

Background

Transdermal administration is an important mode of administration, which avoids gastrointestinal disturbances, prolongs the onset of action, reduces side effects and simplifies the administration process. Various devices have been developed for effective transdermal drug delivery, in which microneedles can penetrate the epidermis without contacting capillaries and nerve endings, thereby facilitating absorption of the drug in a painless, minimally invasive manner. Due to these excellent properties, microneedles are widely used.

Microneedles can be classified into solid microneedles, coated microneedles, soluble microneedles, hollow microneedles, and the like according to different administration modes. In the prior art, micron-sized pores are formed on the surface of skin after the solid micro-needle is inserted and removed, the pores can be convenient for the medicine preparation to pass through, so that the medicine preparation has the function of skin pretreatment under the local action of the skin or through the absorption of capillary vessels of the skin, and the medicine can be applied to the pores on the surface of the skin after the micro-needle pretreats the skin so as to achieve the aim of transdermal administration; the coated microneedle coats the drug on the surface of the microneedle to carry the drug, but the drug loading is low due to the coating method and the drug loading property; the soluble micro-needle is directly made into a needle shape by using a soluble high molecular material, and carries the medicine in the needle shape, but due to the influence of the material performance, the soluble micro-needle has poor mechanical property and can not puncture a skin area with thicker cuticle; the hollow microneedle can directly feed the drug through the hollow microneedle, but has higher manufacturing cost and manufacturing difficulty, and the mechanical property of the needle head is poorer and the needle head is easy to break because the needle head is of a hollow structure.

Therefore, in view of the above technical problems, it is necessary to provide a silicon-based microneedle and a method for preparing the same.

Disclosure of Invention

In view of the above, the present invention aims to provide a silicon-based microneedle and a method for preparing the same.

In order to achieve the above object, an embodiment of the present invention provides the following technical solutions:

a silicon-based ice microneedle comprises a silicon wafer and a plurality of micron needle-shaped structures which are formed on the silicon wafer and distributed in an array mode, wherein a hollow structure penetrating through the top of each micron needle-shaped structure to the bottom of the silicon wafer is formed in each micron needle-shaped structure and the silicon wafer, and an ice soluble needle point is formed in each hollow structure.

In one embodiment, the distance between the micro needle-like structures is 100 to 1000 μm, the height of the micro needle-like structures is 50 to 1000 μm, and the pore diameter of the hollow structures is 20 to 120 μm; and/or the presence of a gas in the gas,

the material with the ice soluble needle tip is one or a combination of water, collagen, polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, polyethylene oxide, polyethylene glycol, polyurethane, polycaprolactone, gelatin, hyaluronic acid, chitosan, hyaluronic acid, silk fibroin and polyvinyl alcohol.

The technical scheme provided by another embodiment of the invention is as follows:

a method for preparing a silicon-based microneedle, the method comprising:

s1, preparing a plurality of micron needle-shaped structures distributed in an array on a silicon wafer, and forming hollow structures penetrating from the top of the micron needle-shaped structures to the bottom of the silicon wafer in the micron needle-shaped structures and the silicon wafer;

and S2, forming the ice soluble needle tip in the hollow structure.

In an embodiment, the step S1 specifically includes:

preparing a barrier dielectric layer on the surface of the silicon wafer;

cutting the blocking dielectric layer to form a patterned mask;

forming a plurality of micron needle-shaped structures distributed in an array on the surface of a silicon wafer by chemical etching in an etching solution;

removing the blocking dielectric layer;

and (3) cutting and punching by laser positioning to form a hollow structure penetrating through the top of the micron needle-shaped structure to the bottom of the silicon wafer.

In one embodiment, in step S1:

the blocking dielectric layer is a silicon oxide layer; and/or the presence of a gas in the gas,

the etching solution is alkaline solution with the mass concentration of 10-50%, the alkaline solution contains one or more of sodium hydroxide and potassium hydroxide, the chemical etching temperature is 50-100 ℃, the chemical etching time is 0.1-12 h, the distance between the micron needle-shaped structures is 100-1000 mu m, and the height of the micron needle-shaped structures is 50-1000 mu m; and/or the presence of a gas in the atmosphere,

the specific steps for removing the blocking medium layer are as follows: placing the silicon slice after chemical etching into hydrofluoric acid solution with mass concentration of 0.1-20% for reaction, and removing the barrier dielectric layer in the non-cutting area, wherein the reaction temperature is 0-50 ℃, and the reaction time is 5-1000 s; and/or the presence of a gas in the gas,

the diameter of the aperture of the hollow structure formed by laser positioning, cutting and punching is 20-120 mu m.

In an embodiment, the step S1 is specifically:

preparing a barrier dielectric layer on the surface of the silicon wafer;

forming a hollow structure penetrating through the silicon wafer and the blocking dielectric layer by laser positioning, cutting and punching;

cutting the blocking dielectric layer to form a patterned mask;

forming a plurality of micron needle-shaped structures which are distributed in an array and have hollow structures on the surface of a silicon wafer through chemical etching in etching liquid;

and removing the barrier dielectric layer.

In one embodiment, in step S1:

the blocking dielectric layer is a silicon oxide layer; and/or the presence of a gas in the gas,

the diameter of the aperture of the hollow structure formed by laser positioning cutting punching is 20-120 μm, and a silicon oxide layer with the thickness of 1-2 μm is formed on the side wall of the hollow structure due to positioning cutting heating; and/or the presence of a gas in the gas,

the etching solution is alkaline solution with the mass concentration of 10-50%, the alkaline solution contains one or more of sodium hydroxide and potassium hydroxide, the chemical etching temperature is 50-100 ℃, the chemical etching time is 0.1-12 h, the distance between the micron needle-shaped structures is 100-1000 mu m, and the height of the micron needle-shaped structures is 50-1000 mu m; and/or the presence of a gas in the gas,

the specific steps for removing the blocking medium layer are as follows: and placing the silicon wafer after chemical etching in a hydrofluoric acid solution with the mass concentration of 0.1-20% for reaction, and removing the barrier dielectric layer in the non-cutting area, wherein the reaction temperature is 0-50 ℃, and the reaction time is 5-1000 s.

In an embodiment, the step S1 specifically includes:

cutting and punching through laser positioning to form a hollow structure penetrating through the silicon wafer;

preparing a blocking dielectric layer on the surface of the silicon wafer and the side wall of the hollow structure;

cutting the blocking dielectric layer to form a patterned mask;

forming a plurality of micron needle-shaped structures which are distributed in an array and have hollow structures on the surface of a silicon wafer through chemical etching in etching liquid;

and removing the barrier dielectric layer.

In one embodiment, in step S1:

the diameter of the aperture of the hollow structure formed by laser positioning cutting punching is 20-120 μm, and a silicon oxide layer with the thickness of 1-2 μm is formed on the side wall of the hollow structure due to positioning cutting heating; and/or the presence of a gas in the atmosphere,

the blocking dielectric layer is a silicon oxide layer; and/or the presence of a gas in the atmosphere,

the etching solution is alkaline solution with the mass concentration of 10-50%, the alkaline solution contains one or more of sodium hydroxide and potassium hydroxide, the chemical etching temperature is 50-100 ℃, the chemical etching time is 0.1-12 h, the distance between the micron needle-shaped structures is 100-1000 mu m, and the height of the micron needle-shaped structures is 50-1000 mu m; and/or the presence of a gas in the gas,

the specific steps for removing the blocking medium layer are as follows: and placing the silicon wafer after chemical etching in a hydrofluoric acid solution with the mass concentration of 0.1-20% for reaction, and removing the barrier dielectric layer in the non-cutting area, wherein the reaction temperature is 0-50 ℃, and the reaction time is 5-1000 s.

In an embodiment, the step S2 specifically includes:

filling solution automatically enters the hollow structure from the bottom of the hollow structure or is forced into the hollow structure from the outside, and freezing treatment is carried out on the filling solution to form an ice soluble needle point in the hollow structure;

wherein, the filling solution is made of one or more of water, collagen, polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, polyethylene oxide, polyethylene glycol, polyurethane, polycaprolactone, gelatin, hyaluronic acid, chitosan, hyaluronic acid, silk fibroin and polyvinyl alcohol;

in the freezing treatment, the freezing temperature is 0 ℃ to 196 ℃ below zero, and the freezing time is 1s to 168 hours.

The invention has the following beneficial effects:

the substrate of the invention adopts the hollow silicon-based microneedle, the preparation process is simple, the cost is lower, and the invention is suitable for large-scale industrial production;

forming ice soluble needle points in the hollow silicon-based microneedles, simplifying the administration steps and improving the drug-loading rate;

the silicon-based ice microneedle improves the mechanical properties of the original hollow silicon-based microneedle and the original soluble microneedle, and solves the problems that the microneedle is easy to break and is difficult to penetrate the skin in the prior art.

Drawings

In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings needed to be used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments described in the present application, and other drawings can be obtained by those skilled in the art without creative efforts.

FIG. 1 is a schematic structural diagram of a silicon-based microneedle according to the present invention;

FIG. 2 is a schematic flow diagram of a silicon-based microneedle according to the present invention;

fig. 3a to 3f are process flow charts of step S1 in the method for preparing silicon-based microneedles according to example 1 of the present invention;

fig. 4a to 4b are process flow charts of step S2 in the method for preparing silicon-based microneedles according to example 1 of the present invention;

fig. 5a to 5e are process flow charts of step S1 in the method for preparing silicon-based microneedles according to example 2 of the present invention;

fig. 6a to 6e are process flow charts of step S1 in the method for preparing silicon-based microneedles according to example 3 of the present invention.

Detailed Description

In order to make those skilled in the art better understand the technical solution of the present invention, the technical solution in the embodiment of the present invention will be clearly and completely described below with reference to the drawings in the embodiment of the present invention, and it is obvious that the described embodiment is only a part of the embodiment of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Referring to fig. 1, a silicon-based ice microneedle comprises a silicon wafer 10 and a plurality of micro needle-like structures 20 formed on the silicon wafer and distributed in an array, wherein hollow structures penetrating from the tops of the micro needle-like structures to the bottoms of the silicon wafer are formed in the micro needle-like structures 20 and the silicon wafer 10, and an ice-soluble needle tip 30 is formed in each hollow structure.

Referring to fig. 2, the invention also discloses a preparation method of the silicon-based ice microneedle, which comprises the following steps:

s1, preparing a plurality of micron needle-shaped structures distributed in an array on a silicon wafer, and forming hollow structures penetrating from the top of the micron needle-shaped structures to the bottom of the silicon wafer in the micron needle-shaped structures and the silicon wafer;

and S2, forming the ice soluble needle tip in the hollow structure.

The present invention will be further described with reference to the following embodiments and examples.

Example 1:

referring to fig. 1, the silicon-based ice microneedle in this embodiment includes a silicon wafer 10 and a plurality of micro needle structures 20 formed on the silicon wafer and distributed in an array, wherein hollow structures penetrating from the top of the micro needle structures to the bottom of the silicon wafer are formed in the micro needle structures 20 and the silicon wafer 10, and an ice soluble needle tip 30 is formed in the hollow structures.

The preparation method of the silicon-based ice microneedle in the embodiment comprises the following steps:

s1, preparing a plurality of micron needle-shaped structures distributed in an array on a silicon wafer, and forming hollow structures penetrating from the top of the micron needle-shaped structures to the bottom of the silicon wafer in the micron needle-shaped structures and the silicon wafer;

and S2, forming the ice soluble needle tip in the hollow structure.

Step S1 in this embodiment specifically includes:

referring to fig. 3a and 3b, a barrier dielectric layer 40 is prepared on the surface of the silicon wafer 10.

Preferably, the blocking dielectric layer in this embodiment is a silicon oxide layer.

Referring to fig. 3c, the blocking dielectric layer 40 is cut to form a patterned mask.

The process for cutting the blocking dielectric layer in the embodiment is a laser cutting process or a water cutting process, and in other embodiments, the patterned mask may be prepared by a photolithography method.

Referring to fig. 3d, a plurality of micron needle-like structures 20 distributed in an array are formed on the surface of the silicon wafer 10 by chemical etching in the etching solution.

Preferably, the etching solution is alkaline solution with the mass concentration of 10-50%, the alkaline solution contains one or more of sodium hydroxide and potassium hydroxide, the chemical etching temperature is 50-100 ℃, the chemical etching time is 0.1-12 h, the distance between the micron needle-shaped structures is 100-1000 μm, and the height of the micron needle-shaped structures is 50-1000 μm.

Referring to fig. 3e, the blocking dielectric layer 40 is removed.

Preferably, in this embodiment, the silicon wafer after chemical etching is placed in a hydrofluoric acid solution with a mass concentration of 0.1% to 20% to react, and the barrier dielectric layer in the non-cutting region is removed, where the reaction temperature is 0 ℃ to 50 ℃ and the reaction time is 5s to 1000 s.

Referring to fig. 3f, holes are cut by laser positioning cutting to form hollow structures 21 penetrating from the top of the micro needle-like structures to the bottom of the silicon wafer.

Preferably, the hollow structure 21 formed by laser positioning cutting punching has a pore diameter of 20 μm to 120 μm.

Step S2 in this embodiment specifically includes:

referring to fig. 4a and 4b, a filling solution is automatically or externally forced into the hollow structure from the bottom of the hollow structure, and is subjected to a freezing process to form an ice-soluble needle tip 30 in the hollow structure, and the needle tip protrudes out of the hollow structure.

Wherein, the filling solution is made of one or more of water, collagen, polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, polyethylene oxide, polyethylene glycol, polyurethane, polycaprolactone, gelatin, hyaluronic acid, chitosan, hyaluronic acid, silk fibroin and polyvinyl alcohol;

preferably, in the freezing treatment, the freezing temperature is 0 ℃ to-196 ℃, and the freezing time is 1s to 168 h.

Example 2:

the silicon-based microneedle structure and the step S2 in the method for manufacturing the silicon-based microneedle structure in this embodiment are completely the same as those in embodiment 1, and are not described herein again.

Different from example 1, step S1 in the preparation method of this embodiment is specifically:

referring to fig. 5a and 5b, a barrier dielectric layer 40 is prepared on the surface of the silicon wafer 10.

Preferably, the blocking dielectric layer in this embodiment is a silicon oxide layer.

Referring to fig. 5c, a hollow structure 21 is formed through the silicon wafer 10 and the blocking dielectric layer 40 by laser positioning dicing via.

Preferably, the diameter of the aperture of the hollow structure formed by the laser positioning cutting punching is 20-120 μm, and a silicon oxide layer with the thickness of 1-2 μm is formed on the side wall of the hollow structure due to the heating of the positioning cutting.

Continuing with fig. 5c, the blocking dielectric layer 40 is cut to form a patterned mask.

The process for cutting the blocking dielectric layer in the embodiment is a laser cutting process or a water cutting process, and in other embodiments, the patterned mask may be prepared by a photolithography method.

Referring to fig. 5d, a plurality of micron needle-like structures 20 with hollow structure are formed on the surface of the silicon wafer by chemical etching in the etching solution.

Preferably, the etching solution is alkaline solution with the mass concentration of 10-50%, the alkaline solution contains one or more of sodium hydroxide and potassium hydroxide, the chemical etching temperature is 50-100 ℃, the chemical etching time is 0.1-12 h, the distance between the micron needle-shaped structures is 100-1000 μm, and the height of the micron needle-shaped structures is 50-1000 μm.

Referring to fig. 5e, the blocking dielectric layer is removed.

Preferably, in this embodiment, the silicon wafer after chemical etching is placed in a hydrofluoric acid solution with a mass concentration of 0.1% to 20% to react, and the barrier dielectric layer in the non-cutting region is removed, where the reaction temperature is 0 ℃ to 50 ℃ and the reaction time is 5s to 1000 s.

Example 3:

the silicon-based microneedle structure and the preparation method in this embodiment have the same steps as those in embodiment 1 in step S2, and are not repeated herein.

Different from example 1, step S1 in the preparation method of this embodiment is specifically:

referring to fig. 6a and 6b, a hollow structure 21 is formed through the silicon wafer 10 by laser positioning dicing.

Preferably, the diameter of the aperture of the hollow structure formed by the laser positioning cutting punching is 20-120 μm, and a silicon oxide layer with the thickness of 1-2 μm is formed on the side wall of the hollow structure due to the heating of the positioning cutting.

Referring to fig. 6c, a blocking dielectric layer 40 is formed on the surface of the silicon wafer 10 and the sidewall of the hollow structure 21.

Preferably, the blocking dielectric layer in this embodiment is a silicon oxide layer.

Continuing with fig. 6c, the blocking dielectric layer 40 is cut to form a patterned mask.

The process for cutting the blocking dielectric layer in the embodiment is a laser cutting process or a water cutting process, and in other embodiments, the patterned mask may be prepared by a photolithography method.

Referring to fig. 6d, a plurality of micron needle-like structures 20 with hollow structures 21 are formed on the surface of the silicon wafer 10 by chemical etching in the etching solution.

Preferably, the etching solution is alkaline solution with the mass concentration of 10-50%, the alkaline solution contains one or more of sodium hydroxide and potassium hydroxide, the chemical etching temperature is 50-100 ℃, the chemical etching time is 0.1-12 h, the distance between the micron needle-shaped structures is 100-1000 μm, and the height of the micron needle-shaped structures is 50-1000 μm.

Referring to fig. 6e, the blocking dielectric layer is removed.

Preferably, in the embodiment, the silicon wafer after chemical etching is placed in a hydrofluoric acid solution with a mass concentration of 0.1% -20% to react, and the barrier dielectric layer in the non-cutting area is removed, wherein the reaction temperature is 0-50 ℃, and the reaction time is 5-1000 s.

According to the technical scheme, the invention has the following advantages:

the substrate of the invention adopts the hollow silicon-based microneedle, the preparation process is simple, the cost is lower, and the invention is suitable for large-scale industrial production;

forming ice soluble needle points in the hollow silicon-based microneedles, simplifying the administration steps and improving the drug-loading rate;

the silicon-based ice microneedle improves the mechanical properties of the original hollow silicon-based microneedle and the original soluble microneedle, and solves the problems that the microneedle is easy to break and is difficult to penetrate the skin in the prior art.

It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof. The present embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein. Any reference sign in a claim should not be construed as limiting the claim concerned.

Furthermore, it should be understood that although the present description refers to embodiments, not every embodiment may contain only a single embodiment, and such description is for clarity only, and those skilled in the art should integrate the description, and the embodiments may be combined as appropriate to form other embodiments understood by those skilled in the art.

Claims (10)

1. The silicon-based ice microneedle is characterized by comprising a silicon wafer and a plurality of micron needle-shaped structures which are formed on the silicon wafer and distributed in an array mode, wherein hollow structures penetrating through the tops of the micron needle-shaped structures to the bottom of the silicon wafer are formed in the micron needle-shaped structures and the silicon wafer, and an ice soluble needle point is formed in each hollow structure.

2. The silicon-based ice microneedle according to claim 1, wherein the pitch between the micro needle-like structures is 100 μm to 1000 μm, the height of the micro needle-like structures is 50 μm to 1000 μm, and the pore diameter of the hollow structure is 20 μm to 120 μm; and/or the presence of a gas in the gas,

the material with the ice soluble needle tip is one or a combination of water, collagen, polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, polyethylene oxide, polyethylene glycol, polyurethane, polycaprolactone, gelatin, hyaluronic acid, chitosan, hyaluronic acid, silk fibroin and polyvinyl alcohol.

3. A preparation method of a silicon-based ice microneedle is characterized by comprising the following steps:

s1, preparing a plurality of micron needle-shaped structures distributed in an array on a silicon wafer, and forming hollow structures penetrating from the top of the micron needle-shaped structures to the bottom of the silicon wafer in the micron needle-shaped structures and the silicon wafer;

and S2, forming the ice soluble needle tip in the hollow structure.

4. The preparation method according to claim 3, wherein the step S1 is specifically:

preparing a barrier dielectric layer on the surface of the silicon wafer;

cutting the blocking dielectric layer to form a patterned mask;

forming a plurality of micron needle-shaped structures distributed in an array on the surface of a silicon wafer by chemical etching in an etching solution;

removing the blocking dielectric layer;

and (3) cutting and punching by laser positioning to form a hollow structure penetrating through the top of the micron needle-shaped structure to the bottom of the silicon wafer.

5. The method according to claim 4, wherein in the step S1:

the blocking dielectric layer is a silicon oxide layer; and/or the presence of a gas in the gas,

the etching solution is alkaline solution with the mass concentration of 10-50%, the alkaline solution contains one or more of sodium hydroxide and potassium hydroxide, the chemical etching temperature is 50-100 ℃, the chemical etching time is 0.1-12 h, the distance between the micron needle-shaped structures is 100-1000 mu m, and the height of the micron needle-shaped structures is 50-1000 mu m; and/or the presence of a gas in the gas,

the specific steps for removing the blocking dielectric layer are as follows: placing the silicon slice after chemical etching into hydrofluoric acid solution with mass concentration of 0.1-20% for reaction, and removing the barrier dielectric layer in the non-cutting area, wherein the reaction temperature is 0-50 ℃, and the reaction time is 5-1000 s; and/or the presence of a gas in the gas,

the diameter of the aperture of the hollow structure formed by laser positioning, cutting and punching is 20-120 mu m.

6. The preparation method according to claim 3, wherein the step S1 is specifically:

preparing a barrier dielectric layer on the surface of the silicon wafer;

forming a hollow structure penetrating through the silicon wafer and the blocking dielectric layer by laser positioning, cutting and punching;

cutting the blocking dielectric layer to form a patterned mask;

forming a plurality of micron needle-shaped structures which are distributed in an array and have hollow structures on the surface of a silicon wafer through chemical etching in etching liquid;

and removing the barrier dielectric layer.

7. The method according to claim 6, wherein in step S1:

the blocking dielectric layer is a silicon oxide layer; and/or the presence of a gas in the gas,

the diameter of the aperture of the hollow structure formed by laser positioning, cutting and punching is 20-120 mu m, and a silicon oxide layer with the thickness of 1-2 mu m is formed on the side wall of the hollow structure due to positioning, cutting and heating; and/or the presence of a gas in the gas,

the etching solution is alkaline solution with the mass concentration of 10-50%, the alkaline solution contains one or more of sodium hydroxide and potassium hydroxide, the chemical etching temperature is 50-100 ℃, the chemical etching time is 0.1-12 h, the distance between the micron needle-shaped structures is 100-1000 mu m, and the height of the micron needle-shaped structures is 50-1000 mu m; and/or the presence of a gas in the gas,

the specific steps for removing the blocking dielectric layer are as follows: and placing the silicon wafer after chemical etching in a hydrofluoric acid solution with the mass concentration of 0.1-20% for reaction, and removing the barrier dielectric layer in the non-cutting area, wherein the reaction temperature is 0-50 ℃, and the reaction time is 5-1000 s.

8. The preparation method according to claim 3, wherein the step S1 is specifically:

cutting and punching through laser positioning to form a hollow structure penetrating through the silicon wafer;

preparing a blocking dielectric layer on the surface of the silicon wafer and the side wall of the hollow structure;

cutting the blocking dielectric layer to form a patterned mask;

forming a plurality of micron needle-shaped structures which are distributed in an array and have hollow structures on the surface of a silicon wafer through chemical etching in etching liquid;

and removing the barrier dielectric layer.

9. The method according to claim 8, wherein in step S1:

the diameter of the aperture of the hollow structure formed by laser positioning, cutting and punching is 20-120 mu m, and a silicon oxide layer with the thickness of 1-2 mu m is formed on the side wall of the hollow structure due to positioning, cutting and heating; and/or the presence of a gas in the gas,

the blocking dielectric layer is a silicon oxide layer; and/or the presence of a gas in the gas,

the etching solution is alkaline solution with the mass concentration of 10-50%, the alkaline solution contains one or more of sodium hydroxide and potassium hydroxide, the chemical etching temperature is 50-100 ℃, the chemical etching time is 0.1-12 h, the distance between the micron needle-shaped structures is 100-1000 mu m, and the height of the micron needle-shaped structures is 50-1000 mu m; and/or the presence of a gas in the atmosphere,

the specific steps for removing the blocking medium layer are as follows: and placing the silicon wafer after chemical etching in a hydrofluoric acid solution with the mass concentration of 0.1-20% for reaction, and removing the barrier dielectric layer in the non-cutting area, wherein the reaction temperature is 0-50 ℃, and the reaction time is 5-1000 s.

10. The preparation method according to claim 3, wherein the step S2 is specifically:

filling solution automatically enters the hollow structure from the bottom of the hollow structure or is forced into the hollow structure from the outside, and freezing treatment is carried out on the filling solution to form an ice soluble needle point in the hollow structure;

wherein, the filling solution is made of one or more of water, collagen, polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, polyethylene oxide, polyethylene glycol, polyurethane, polycaprolactone, gelatin, hyaluronic acid, chitosan, hyaluronic acid, silk fibroin and polyvinyl alcohol;

in the freezing treatment, the freezing temperature is 0 ℃ to 196 ℃ below zero, and the freezing time is 1s to 168 hours.

Images