CN111135450A - Microneedle with boss structure and preparation method thereof - Google Patents
Microneedle with boss structure and preparation method thereof Download PDFInfo
- Publication number
- CN111135450A CN111135450A CN202010036590.9A CN202010036590A CN111135450A CN 111135450 A CN111135450 A CN 111135450A CN 202010036590 A CN202010036590 A CN 202010036590A CN 111135450 A CN111135450 A CN 111135450A
- Authority
- CN
- China
- Prior art keywords
- microneedle
- silicon
- boss structure
- protective film
- silicon substrate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
-
- C—CHEMISTRY; METALLURGY
- C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
- C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
- C23C16/00—Chemical coating by decomposition of gaseous compounds, without leaving reaction products of surface material in the coating, i.e. chemical vapour deposition [CVD] processes
- C23C16/02—Pretreatment of the material to be coated
-
- C—CHEMISTRY; METALLURGY
- C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
- C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
- C23C16/00—Chemical coating by decomposition of gaseous compounds, without leaving reaction products of surface material in the coating, i.e. chemical vapour deposition [CVD] processes
- C23C16/04—Coating on selected surface areas, e.g. using masks
- C23C16/042—Coating on selected surface areas, e.g. using masks using masks
-
- C—CHEMISTRY; METALLURGY
- C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
- C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
- C23C16/00—Chemical coating by decomposition of gaseous compounds, without leaving reaction products of surface material in the coating, i.e. chemical vapour deposition [CVD] processes
- C23C16/22—Chemical coating by decomposition of gaseous compounds, without leaving reaction products of surface material in the coating, i.e. chemical vapour deposition [CVD] processes characterised by the deposition of inorganic material, other than metallic material
- C23C16/30—Deposition of compounds, mixtures or solid solutions, e.g. borides, carbides, nitrides
- C23C16/34—Nitrides
- C23C16/345—Silicon nitride
-
- C—CHEMISTRY; METALLURGY
- C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
- C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
- C23C16/00—Chemical coating by decomposition of gaseous compounds, without leaving reaction products of surface material in the coating, i.e. chemical vapour deposition [CVD] processes
- C23C16/44—Chemical coating by decomposition of gaseous compounds, without leaving reaction products of surface material in the coating, i.e. chemical vapour deposition [CVD] processes characterised by the method of coating
- C23C16/50—Chemical coating by decomposition of gaseous compounds, without leaving reaction products of surface material in the coating, i.e. chemical vapour deposition [CVD] processes characterised by the method of coating using electric discharges
-
- C—CHEMISTRY; METALLURGY
- C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
- C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
- C23C16/00—Chemical coating by decomposition of gaseous compounds, without leaving reaction products of surface material in the coating, i.e. chemical vapour deposition [CVD] processes
- C23C16/56—After-treatment
-
- C—CHEMISTRY; METALLURGY
- C30—CRYSTAL GROWTH
- C30B—SINGLE-CRYSTAL GROWTH; UNIDIRECTIONAL SOLIDIFICATION OF EUTECTIC MATERIAL OR UNIDIRECTIONAL DEMIXING OF EUTECTOID MATERIAL; REFINING BY ZONE-MELTING OF MATERIAL; PRODUCTION OF A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; SINGLE CRYSTALS OR HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; AFTER-TREATMENT OF SINGLE CRYSTALS OR A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; APPARATUS THEREFOR
- C30B33/00—After-treatment of single crystals or homogeneous polycrystalline material with defined structure
- C30B33/005—Oxydation
-
- C—CHEMISTRY; METALLURGY
- C30—CRYSTAL GROWTH
- C30B—SINGLE-CRYSTAL GROWTH; UNIDIRECTIONAL SOLIDIFICATION OF EUTECTIC MATERIAL OR UNIDIRECTIONAL DEMIXING OF EUTECTOID MATERIAL; REFINING BY ZONE-MELTING OF MATERIAL; PRODUCTION OF A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; SINGLE CRYSTALS OR HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; AFTER-TREATMENT OF SINGLE CRYSTALS OR A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; APPARATUS THEREFOR
- C30B33/00—After-treatment of single crystals or homogeneous polycrystalline material with defined structure
- C30B33/02—Heat treatment
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0023—Drug applicators using microneedles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/003—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles having a lumen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0046—Solid microneedles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0053—Methods for producing microneedles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0061—Methods for using microneedles
Abstract
The invention discloses a microneedle with a single or multiple boss structure and a preparation method thereof, comprising the steps of monocrystalline silicon substrate purification, preparation of monocrystalline silicon substrate protective film, patterning of the silicon substrate protective film, boss preparation, microneedle body preparation and aftertreatment; the invention has the advantages that the nano monocrystalline silicon microneedle with the boss structure can penetrate through the stratum corneum of the skin without touching the corium and the subcutaneous nervous system, a channel is created for the medium of biological medicines and the like to enter in the skin under the condition of not causing skin pain and stimulation, and meanwhile, the existence of the boss structure can effectively expand a channel introduced in the skin and expand the storage space of the medium of the biological medicines, thereby being more beneficial to leading the medium of the biological medicines and the like into the skin and absorbing the medium.
Description
Technical Field
The invention relates to the field of transdermal drug release devices, in particular to a nano microneedle with a boss structure and a preparation method thereof.
Background
Transdermal administration usually involves subcutaneous injection, and has disadvantages such as pain, operation by a professional, infection at the injection site, and tissue damage. However, although the existing transdermal delivery methods such as drug coating and plaster patch are painless and convenient to use, the barrier formed by the skin cuticle layer can prevent more than 95% of the absorption of the drugs and nutrients, and especially the macromolecular drugs are more difficult to break through the cuticle barrier.
The micro-needle is a percutaneous administration technology with a good application prospect, is a novel physical permeation-promoting means, can easily penetrate through the stratum corneum of the skin without touching the corium layer, subcutaneous nerves and blood vessels, and cannot cause skin pain, discomfort and bleeding. It combines the advantages of traditional transdermal drug delivery and transdermal drug delivery, can achieve painless, accurate and rapid drug delivery, and simultaneously avoids skin injury and infection. Microneedle technology has been widely used not only in the biomedical field but also in the medical cosmetic field, and microneedles have excellent application prospects in the aspects of resisting skin water deficit, resisting skin aging, resisting skin pigmentation, treating dry skin, treating acne, reducing fat, and the like, and have been used in europe, the united states, japan, korea, and the like.
Most of the existing nano microneedles are monocrystalline silicon nano microneedles, the structures are conical structures, the sizes of needle points can reach the nanometer level, nanometer-level micro channels can be formed in the skin stratum corneum, and medicines or nutrients can penetrate through the skin stratum corneum barrier and directly act on the skin dermis, but because the incision channels are too small, the absorption of the medicines and the nutrients is limited.
Disclosure of Invention
1. Technical problem to be solved
The invention solves the technical problem that the microneedle with the boss structure is provided, aiming at the problem that the existing monocrystal silicon nanometer microneedle forms a tiny channel on the skin cuticle, which is too small, and limits the speed of a biological medicine medium passing through the skin cuticle barrier, the invention designs the nanometer monocrystal silicon microneedle with the boss structure, which can penetrate the skin cuticle without touching the corium and a subcutaneous nervous system, creates a channel for the percutaneous entering of the medium such as biological medicine under the condition of not causing skin pain and stimulation, and the existence of the boss structure can effectively expand a channel introduced through the skin and expand the storage space of the biological medicine macromolecule medium; the microneedle with the boss structure has the advantages that the effective height of a needle body is 1-2000 mu m, the size of a needle point is 1 nm-50 mu m, and the size of the bottom connected with a support body is 1-2000 mu m; each needle body is provided with one or more boss structures; the boss structure is positioned at the upper part of the microneedle body and below the needle point, and the distance between the maximum size position of the boss structure closest to the needle point and the needle point is not more than 100 mu m; the boss structure comprises but is not limited to one of a sphere, an ellipsoid or a polygonal cone, the size of the boss structure is 1 nm-100 mu m, and the maximum size of the boss structure is not smaller than the size of the needle body connected with the boss structure; the microneedle with the boss structure can pierce the stratum corneum of the skin to form and expand the medium introducing channel and the medium storage space, does not cause pain and skin irritation, and is more favorable for introducing macromolecular media such as biological medicines into the skin and absorbing the macromolecular media.
2. Technical scheme
In order to achieve the purpose, the invention provides the following technical scheme: a nanometer microneedle with a boss structure comprises a support body and a microneedle array with a boss structure; the microneedle body is of a conical or multi-pyramid structure with a small upper part and a large lower part, the effective height of a needle body is 1-2000 mu m, the size of a needle point is 1 nm-50 mu m, and the size of the joint of the microneedle body and the support body is 1-2000 mu m; the microneedle body extends along the radial direction to form one or more boss structures, and the boss structures and the microneedle body are in curve or are in direct transitional connection; the cross-sectional shape of the boss structure includes, but is not limited to, one of a circle, an ellipse, or a polygon.
The nano microneedle with the boss structure is characterized in that the maximum width of the boss structure is 1 nm-100 mu m; the maximum width of the boss structure is not less than the size of the microneedle body connected with the boss structure.
The microneedle with the boss structure is characterized in that the projection length of the distance between the maximum width position of the boss structure closest to the needle point of the microneedle body and the top surface of the microneedle body on the axis of the microneedle body is not more than 100 micrometers.
The microneedle with the boss structure is characterized in that the microneedle body can be a solid needle body or a hollow needle body.
The microneedle with the boss structure is characterized in that the hollow microneedle body is provided with an opening along the axial direction, and the opening can be a through hole from the bottom surface of the support body to the needle point, or a non-through hole from the bottom surface of the support body to the middle part of the microneedle body or below the needle point.
The microneedle with the boss structure is characterized in that the cross-sectional shape of the through hole or the non-through hole formed on the bottom surface of the hollow microneedle body along the axial direction includes but is not limited to one of a circle, an ellipse or a polygon.
The microneedle with the boss structure is characterized in that the support and the nano microneedle array material include but are not limited to monocrystalline silicon, monocrystalline germanium, glass, organic glass, stainless steel, nickel, copper, aluminum and other metal materials.
The microneedle with the boss structure is characterized in that the surface of the support body and the surface of the microneedle body with the boss structure are coated with a silicon nitride film or a metal titanium film.
The invention also discloses a method for preparing the nano microneedle with the boss structure by using the monocrystalline silicon material, which comprises the following steps:
and 3.1, uniformly coating a layer of photoresist on one surface of the silicon substrate, wherein the thickness of the photoresist is 1-20 microns, pre-drying the photoresist at the temperature of 80-120 ℃, covering a mask with a designed pattern, exposing for 5-100 seconds, developing and drying.
Further, etching the silicon dioxide or silicon nitride protective film at the exposure position by using wet etching or ion beams to form a required pattern on the silicon substrate protective film;
step 3.2, coating photoresist on the first surface of the silicon substrate, covering a circular, triangular or polygonal mask, exposing, developing and drying;
further, etching the silicon dioxide or silicon nitride protective film at the exposed part of the first surface of the silicon substrate by using wet etching or ion beams to form a required pattern on the protective film of the first surface of the silicon substrate;
further, deep silicon etching is carried out by an anisotropic dry method to form a through hole or a non-through hole;
further, generating a silicon nitride protective film on the inner wall of the hole by using a plasma vapor deposition method;
further, coating photoresist on the second surface of the silicon substrate, covering a mask with a designed pattern, exposing, developing and drying;
further, etching the silicon dioxide or silicon nitride protective film at the exposure position by using wet etching or ion beams to form a required pattern on the silicon substrate protective film;
step 4.1, etching the silicon substrate with the patterned protective film for the first time by using an isotropic process;
step 4.2, carrying out first side wall passivation;
4.3, removing the bottom passivation layer by plasma bombardment for the first time;
4.4, etching by a second isotropic process;
step 4.5, passivating the side wall for the second time to form a first boss; 4.6, removing the bottom passivation layer by using plasma bombardment for the second time;
4.7, if a plurality of boss structures need to be prepared, repeating the steps 4.1-4.6;
step 4.8, deep silicon etching is carried out by using an anisotropic process to form a microneedle body;
step 4.9, isotropic etching is carried out until the needle point of the microneedle body is formed;
preferably, the standard cleaning solution RCA1 in the step 1 is a mixed solution of water and 25% ammonia water, which can clean organic dirt on the surface of a silicon substrate, and since ammonia water is corrosive to the silicon wafer, a proper amount of peroxide can be added to effectively prevent the silicon substrate from being corroded.
Preferably, the temperature range for preparing the silicon dioxide protective film by the high-temperature thermal oxidation in the step 2 is 700-1200 ℃, and silicon dioxide films with the thickness of 100nm-10 μm are respectively formed on two surfaces of the silicon substrate.
Preferably, the thickness of the silicon nitride protective layer prepared by the plasma enhanced chemical vapor deposition method in the step 2 is 100nm-10 μm.
Preferably, in the step 3.2, when the silicon substrate is patterned in the step of preparing the hollow silicon micro-needle, the holes formed on the first surface by anisotropic deep silicon etching may or may not penetrate through the silicon substrate.
Preferably, in step 3.2, when the silicon substrate is patterned in the step of preparing the hollow silicon microneedle, the holes formed in the second surface pattern and the holes formed in the first surface may be concentric or non-concentric, but the minimum size of the second surface pattern should be completely larger than the maximum size of the holes in the first surface, that is, the second surface pattern completely covers the holes in the first surface.
Preferably, in step 3, the wet etching solution includes an etching solution and a slow-release solution, wherein the etching solution is a mixed solution of hydrofluoric acid and nitric acid.
Preferably, in step 4, when the bump is prepared, the second isotropic etching time in step 4.4 is longer than the first isotropic etching time in step 4.1, and the range of removing the bottom passivation layer in step 4.6 by the second plasma bombardment is not more than the range of removing the bottom passivation layer in step 4.3 by the first plasma bombardment.
Preferably, in the step 5, a silicon nitride film or a metal titanium film is deposited by using a chemical vapor deposition method, a physical vapor deposition method or a sputtering method, wherein the thickness of the silicon nitride film is 1-10 μm, and the thickness of the metal titanium film is 10nm-1 μm.
3. Advantageous effects
In conclusion, the beneficial effects of the invention are as follows:
(1) the invention designs the nano microneedle with the boss structure, which can penetrate the stratum corneum of the skin without touching the dermis and the subcutaneous nervous system, and creates a channel for the percutaneous entry of mediums such as biomedicine and the like under the condition of not causing skin pain and stimulation;
(2) the boss structure of the nano microneedle can effectively expand a percutaneous introduced passage and a biomedical medium storage space, and is more beneficial to introducing and absorbing the biomedical medium and other media into the skin.
Drawings
FIG. 1 is a flow chart of an embodiment of the present invention for preparing a solid silicon microneedle with a single mesa structure;
FIG. 2 is a schematic view of a solid microneedle structure with a single plateau formation according to an embodiment of the present invention;
FIG. 3 is a schematic view of a solid microneedle array with three plateau formation according to the present invention;
FIG. 4 is a flow chart of an embodiment of the present invention for preparing a hollow silicon microneedle with a single boss structure and a through hole;
FIG. 5 is a perspective view of a hollow microneedle structure with a single plateau formation and a through-penetration hole according to an embodiment of the present invention;
FIG. 6 is a perspective view of a hollow microneedle structure with a single boss structure and a non-penetrating hole according to an embodiment of the present invention;
FIG. 7 is a schematic view of a hollow microneedle array with a single plateau formation and with through holes according to an embodiment of the present invention;
in the figure, 1-microneedle body; 2-boss structure; 3-a support; 4-through holes of hollow microneedles; 5. non-penetrating holes of hollow microneedles.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the 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.
Fig. 1 shows a flow chart of an embodiment of the present invention for preparing a solid silicon microneedle with a single mesa structure.
Firstly, thermally oxidizing a purified monocrystalline silicon substrate at the high temperature of 700-1200 ℃, and respectively forming silicon dioxide protective films with the thickness of 100nm-10 mu m on two surfaces of the silicon substrate; or preparing a silicon nitride protective film with the thickness of 100nm-10 mu m by adopting a plasma enhanced chemical vapor deposition method;
further, uniformly coating a layer of photoresist on one surface of the silicon substrate, wherein the thickness of the photoresist is 1-20 microns, pre-drying the photoresist at 80-120 ℃, covering a mask with a designed pattern, exposing the mask for 5-100 seconds, developing the mask and drying the mask at 80-150 ℃;
further, etching the silicon dioxide or silicon nitride protective film at the exposure position by using wet etching or ion beams to form a required pattern on the silicon substrate protective film;
further, the wet etching solution comprises an etching solution and a slow release solution, wherein the etching solution is a mixed solution of hydrofluoric acid and nitric acid;
further, etching the silicon substrate with the patterned protective film by using an isotropic process for the first time to form spherical pits between the silicon substrate protective films, and then performing side wall passivation for the first time;
further, bombarding the bottom of the spherical pit by using plasma, and removing the bottom passivation layer;
further, etching for the second time by using an isotropic process, and performing spherical deep digging again on the basis of the spherical pits to form 8-shaped pits;
furthermore, the etching time of the second isotropic process is longer than that of the first isotropic process, and the size of a spherical pit formed by the second isotropic process is larger than that of a pit formed by the first isotropic process;
further, carrying out secondary side wall passivation;
further, bombarding the bottom of the spherical pit with plasma for the second time, removing the bottom passivation layer, and forming a first boss structure 2;
further, if more boss structures 2 need to be prepared, repeating the first isotropic etching process, the first side wall passivation, the first bottom passivation layer removal, the second isotropic etching process, the second side wall passivation and the second bottom passivation layer removal;
further, the range of removing the bottom passivation layer by the secondary plasma bombardment is not more than the range of removing the bottom passivation layer by the primary plasma bombardment;
further, anisotropic deep silicon etching is used for forming the micro-needle body 1;
further, forming a needle tip of the microneedle body 1 by isotropic etching;
further, a silicon nitride film with the thickness of 1-10 mu m or a metallic titanium film with the thickness of 10nm-1 mu m is deposited by a chemical vapor deposition method, a physical vapor deposition method or a sputtering method, so that the mechanical property and the biocompatibility of the microneedle are improved.
FIG. 2 is a schematic diagram of a single solid silicon microneedle with a boss, which comprises a microneedle body 1 and a boss structure 2, wherein the effective height of the microneedle body 1 is 1-2000 μm, the size of a needle point is 1 nm-50 μm, and the maximum size of a joint of the bottom and a support body 3 is 1-2000 μm;
further, the microneedle body 1 extends along the radial direction to form one or more boss structures 2, and the boss structures 2 and the microneedle body 1 are in transition connection in a curve or straight line; fig. 2 is a schematic diagram of a microneedle structure with a single plateau structure, and fig. 3 is a schematic diagram of a microneedle array with three plateau structures;
further, the projection length of the distance between the maximum width position of the boss structure 2 closest to the needle point of the microneedle body 1 and the top surface of the microneedle body 1 on the axis of the microneedle body 1 is not more than 100 μm. Further, the maximum size of the boss structure 2 is 1 nm-100 μm, and the maximum size is not smaller than the size of the microneedle body 1 connected with the boss structure;
further, the shape of the boss structure 2 includes, but is not limited to, one of a spherical shape, an elliptical spherical shape, or a polygonal cone shape;
furthermore, the concave-convex array formed in the etching process exists on the surface of the microneedle body 1, so that the contact area with media such as biological medicines is increased, and the drug loading capacity is improved;
furthermore, a layer of silicon nitride film with the thickness of 1-10 μm or a layer of metal titanium film with the thickness of 10nm-1 μm is prepared on the array surface of the support body 3 and the microneedle body 1 with the boss structure 2, so that the mechanical property and the biocompatibility of the microneedle are improved;
fig. 3 is a schematic diagram of a nano microneedle array with three boss structures, in which the microneedle body 1 is a solid needle body, and the three boss structures 2 are arranged along the axial direction of the microneedle body 1.
FIG. 4 is a flow chart showing an embodiment of the present invention for preparing a hollow silicon microneedle with a boss, in which, like the preparation of a solid microneedle, a single crystal silicon substrate is first purified and silicon substrate protective films are prepared on both sides;
further, preparing a silicon dioxide protective film with the thickness of 100nm-10 mu m by high-temperature thermal oxidation at 700-1200 ℃; or preparing a silicon nitride protective film with the thickness of 100nm-10 mu m by adopting a plasma enhanced chemical vapor deposition method;
further, uniformly coating a layer of photoresist on the first surface of the silicon substrate, wherein the thickness of the photoresist is 1-20 microns, pre-drying the photoresist at 80-120 ℃, covering a circular, triangular or polygonal mask, exposing the photoresist for 5-100 seconds, developing the photoresist and drying the photoresist at 80-150 ℃;
further, etching the silicon dioxide or silicon nitride protective film at the exposed part of the first surface of the silicon substrate by using wet etching or ion beams to form a required pattern on the protective film of the first surface of the silicon substrate;
further, the wet etching solution comprises an etching solution and a slow release solution, wherein the etching solution is a mixed solution of hydrofluoric acid and nitric acid;
further, deep silicon etching is carried out by an anisotropic dry method to form a hole;
furthermore, the holes can be in a circular column shape, a triangular column shape or a polygonal column shape;
furthermore, the through hole 4 can be prepared by penetrating the depth of the hole through the silicon substrate, and the non-through hole 5 can also be prepared without penetrating the silicon substrate;
further, generating a silicon nitride protective film on the inner wall of the hole by using a plasma vapor deposition method, wherein the thickness of the silicon nitride protective film is 100nm-10 mu m;
further, uniformly coating a layer of photoresist on the second surface of the silicon substrate, wherein the thickness of the photoresist is 1-20 microns, pre-drying the photoresist at 80-120 ℃, covering a mask with a designed pattern, exposing the mask for 5-100 seconds, developing the mask and drying the mask at 80-150 ℃;
furthermore, the design pattern of the second mask and the design pattern of the first mask can be concentric or non-concentric, but the minimum dimension of the second mask should be completely larger than the maximum dimension of the first mask, that is, the second mask completely covers the first mask;
further, etching the silicon dioxide or silicon nitride protective film at the exposure position by using wet etching or ion beams to prepare a second surface protective film of the silicon substrate for patterning;
further, etching the silicon substrate with the patterned protective film by using an isotropic process for the first time to form spherical pits between the silicon substrate protective films, and then performing side wall passivation for the first time;
further, bombarding the bottom of the spherical pit by using plasma, and removing the bottom passivation layer;
further, etching for the second time by using an isotropic process, and performing spherical deep digging again on the basis of the spherical pits to form 8-shaped pits;
furthermore, the etching time of the second isotropic process is longer than that of the first isotropic process, and the size of a spherical pit formed by the second isotropic process is larger than that of a pit formed by the first isotropic process;
further, carrying out secondary side wall passivation;
further, bombarding the bottom of the spherical pit with plasma for the second time, removing the bottom passivation layer, and forming a first boss structure 2;
further, if more boss structures 2 need to be prepared, repeating the first isotropic etching process, the first side wall passivation, the first bottom passivation layer removal, the second isotropic etching process, the second side wall passivation and the second bottom passivation layer removal;
further, the range of removing the bottom passivation layer by the secondary plasma bombardment is not more than the range of removing the bottom passivation layer by the primary plasma bombardment;
further, anisotropic deep silicon etching is used for forming the micro-needle body 1;
further, forming a needle tip by isotropic etching;
further, a silicon nitride film with the thickness of 1-10 mu m or a metallic titanium film with the thickness of 10nm-1 mu m is deposited by a chemical vapor deposition method, a physical vapor deposition method or a sputtering method, so that the mechanical property and the biocompatibility of the microneedle are improved.
FIG. 5 is a perspective view of a hollow silicon microneedle with a single boss structure and a through hole according to the present invention, wherein the effective height of the needle body is 1-2000 μm, the size of the needle tip is 1 nm-50 μm, and the size of the junction between the bottom of the needle body and the support body is 1-2000 μm;
further, the boss structure 2 is positioned below the upper needle point of the microneedle body 1, and the distance between the maximum size of the boss structure and the top surface of the microneedle body 1 is not more than 100 μm;
further, the size of the boss structure 2 is 1 nm-100 μm, and the maximum size is not smaller than the size of the microneedle body 1 connected with the boss structure;
further, the convex structure table 2 can be spherical, elliptical or polygonal conical;
furthermore, a through hole 4 which is opened from the bottom of the support body 3 to the needle point of the microneedle is formed in the hollow needle body along the axial direction of the microneedle body;
fig. 7 is a schematic view of a hollow microneedle array with a single boss structure and a through hole according to an embodiment of the present invention, in which the microneedle body 1 is a hollow needle body, and a through hole 4 is axially formed along the microneedle body from the bottom of the supporting body 3 to the tip of the microneedle. The hollow microneedle with the through hole 4 is provided with a single boss structure 2.
Fig. 6 is a perspective view of a hollow microneedle structure with a single boss structure and a non-through hole according to the present invention, wherein the microneedle body 1 is provided with a hole 5 along an axial direction from the bottom of the support body 3, and the hole 5 extends along the axial direction from the bottom of the support body 3 and is a non-through hole not reaching the tip of the microneedle;
further, a layer of silicon nitride protective film is prepared on the surface of the through hole 4 and the surface of the non-through hole 5 of the microneedle body 1, and the thickness of the silicon nitride protective film is 100nm-10 mu m;
further, the shape of the through-hole 4 or the non-through-hole 5 includes, but is not limited to, a circular column, a triangular column, or a polygonal column structure;
furthermore, the concave-convex array formed in the etching process exists on the surface of the microneedle body 1, so that the contact area with media such as biological medicines is increased, and the drug loading capacity is improved;
furthermore, a layer of silicon nitride film with the thickness of 1-10 μm or a layer of metal titanium film with the thickness of 10nm-1 μm is prepared on the surface of the microneedle body 1, so that the mechanical property and the biocompatibility of the microneedle are improved.
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (10)
1. The utility model provides a micropin with boss structure which characterized in that: comprises a support body (3) and a micro-needle body (1) array with a boss structure (2); the microneedle body (1) is of a conical or polygonal pyramid structure with a small upper part and a large lower part, the effective height of the microneedle body is 1-2000 mu m, the size of a needle point is 1 nm-50 mu m, and the size of the joint of the microneedle body (1) and the support body (3) is 1-2000 mu m; the micro-needle body (1) extends along the radial direction to form one or more boss structures (2), and the boss structures (2) are in transition connection with the micro-needle body (1) in a curve or straight line manner; the cross-sectional shape of the boss structure (2) includes but is not limited to one of a circle, an ellipse or a polygon.
2. A microneedle with a plateau structure according to claim 1, wherein: one or more boss structures (2) can be prepared on the microneedle body (1); the projection length of the distance between the maximum width position of the boss structure (2) closest to the needle point of the microneedle body (1) and the top surface of the microneedle body (1) on the axis of the microneedle body (1) is not more than 100 mu m.
3. A microneedle with a plateau structure according to claim 1, wherein: the maximum width of the boss structure (2) is 1 nm-100 mu m; the maximum width of the boss structure (2) is not less than the size of the microneedle body (1) connected with the boss structure.
4. A microneedle with a plateau structure according to claim 1, wherein: the micro-needle body (1) can be a solid needle body or a hollow needle body; the hollow microneedle (1) is provided with an opening along the axial direction, the opening can be a through hole (4) from the bottom surface of the support body (3) to the needlepoint, and also can be a non-through hole (5) from the bottom surface of the support body to the middle part of the microneedle body or below the needlepoint, and the cross section shapes of the through hole (4) and the non-through hole (5) comprise but are not limited to one of a circle, an ellipse or a polygon.
5. A method for preparing monocrystalline silicon by using the microneedle with the boss structure as claimed in any one of claims 1 to 4, comprising the steps of:
step 1, purifying a monocrystalline silicon substrate: cleaning with mixed solution of standard cleaning solution RCA1 and peroxide, cleaning with deionized water, and dewatering;
step 2, preparing a monocrystalline silicon substrate protective film: the silicon dioxide protective film can be prepared by high-temperature thermal oxidation, or the silicon nitride protective film can be prepared by a plasma enhanced chemical vapor deposition method;
step 3, patterning of the silicon substrate protective film: the solid silicon micro-needle performs step 3.1, the hollow silicon micro-needle performs step 3.2:
and 3.1, uniformly coating a layer of photoresist on one surface of the silicon substrate, wherein the thickness of the photoresist is 1-20 microns, pre-drying the photoresist at the temperature of 80-120 ℃, covering a mask with a designed pattern, exposing for 5-100 seconds, developing and drying.
Further, etching the silicon dioxide or silicon nitride protective film at the exposure position by using wet etching or ion beams to form a required pattern on the silicon substrate protective film;
step 3.2, coating photoresist on the first surface of the silicon substrate, covering a circular, triangular or polygonal mask, exposing, developing and drying;
further, etching the silicon dioxide or silicon nitride protective film at the exposed part of the first surface of the silicon substrate by using wet etching or ion beams to form a required pattern on the protective film of the first surface of the silicon substrate;
further, anisotropic dry deep silicon etching is used for forming a through hole (4) or a non-through hole (5);
further, generating a silicon nitride protective film on the inner wall of the hole by using a plasma vapor deposition method;
further, coating photoresist on the second surface of the silicon substrate, covering a mask with a designed pattern, exposing, developing and drying;
further, etching the silicon dioxide or silicon nitride protective film at the exposure position by using wet etching or ion beams to form a required pattern on the silicon substrate protective film;
step 4, preparing the boss and the microneedle body, comprising the following steps:
step 4.1, etching the silicon substrate with the patterned protective film for the first time by using an isotropic process;
step 4.2, carrying out first side wall passivation;
4.3, removing the bottom passivation layer by plasma bombardment for the first time;
4.4, etching by a second isotropic process;
step 4.5, passivating the side wall for the second time;
4.6, removing the bottom passivation layer by using plasma bombardment for the second time to form a boss structure (2);
4.7, if a plurality of boss structures (2) are required to be prepared, repeating the steps 4.1-4.6;
step 4.8, deep silicon etching is carried out by using an anisotropic process to form a microneedle body (1);
step 4.9, carrying out isotropic etching until the needle point of the microneedle body (1) is formed;
and 5, post-treatment, namely depositing a silicon nitride film or a metallic titanium film by using a chemical vapor deposition method, a physical vapor deposition method or a sputtering method to increase the mechanical property and the biocompatibility of the microneedle body (1).
6. The method for preparing a microneedle with a boss structure according to claim 5, wherein: the temperature range of the silicon dioxide protective film prepared by the high-temperature thermal oxidation in the step 2 is 700-1200 ℃, and silicon dioxide films of 100nm-10 mu m are respectively formed on two sides of the silicon substrate.
7. The method for preparing a microneedle with a boss structure according to claim 5, wherein: the thickness of the silicon nitride protective layer prepared by the plasma enhanced chemical vapor deposition method in the step 2 is 100nm-10 mu m.
8. The method for preparing a microneedle with a boss structure according to claim 5, wherein: in the step 3.2, when the silicon substrate is patterned in the step of preparing the hollow silicon micro-needle, the through hole (4) or the non-through hole (5) formed on the second surface pattern and the first surface may be concentric or non-concentric, but the minimum dimension of the second surface pattern should be completely larger than the maximum dimension of the through hole (4) or the non-through hole (5) on the first surface, that is, the second surface pattern completely covers the hole on the first surface.
9. The method for preparing a microneedle with a boss structure according to claim 5, wherein: in the step 4, when the boss structure (2) is prepared, the second isotropic etching time is longer than the first isotropic etching time, and the range of removing the bottom passivation layer by the second plasma bombardment is not more than the range of removing the bottom passivation layer by the first plasma bombardment.
10. The method for preparing a microneedle with a boss structure according to claim 5, wherein: in the step 5, a layer of silicon nitride film or metal titanium film is deposited by using a chemical vapor deposition method, a physical vapor deposition method or a sputtering method, wherein the thickness of the silicon nitride film is 1-10 mu m, and the thickness of the metal titanium film is 10nm-1 mu m.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010036590.9A CN111135450A (en) | 2020-01-14 | 2020-01-14 | Microneedle with boss structure and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010036590.9A CN111135450A (en) | 2020-01-14 | 2020-01-14 | Microneedle with boss structure and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111135450A true CN111135450A (en) | 2020-05-12 |
Family
ID=70525152
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010036590.9A Pending CN111135450A (en) | 2020-01-14 | 2020-01-14 | Microneedle with boss structure and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111135450A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112410867A (en) * | 2020-11-05 | 2021-02-26 | 中国航发北京航空材料研究院 | Processing method of high-temperature alloy close-packed hole column array structure |
| CN112779516A (en) * | 2020-12-22 | 2021-05-11 | 苏州恒之清生物科技有限公司 | Crystalline silicon microneedle with hard coating protection and preparation method thereof |
| CN112807561A (en) * | 2021-01-26 | 2021-05-18 | 上海烨映微电子科技股份有限公司 | Microneedle structure and method for producing same |
| CN113443603A (en) * | 2021-06-30 | 2021-09-28 | 苏州恒之清生物科技有限公司 | Preparation method of superfine hollow microneedle chip |
| CN114849051A (en) * | 2022-04-02 | 2022-08-05 | 相邦(苏州)生物材料科技有限公司 | Preparation method of silicon-based microneedle |
| JP7464465B2 (en) | 2020-06-29 | 2024-04-09 | 花王株式会社 | Micro hollow protrusion tool |
-
2020
- 2020-01-14 CN CN202010036590.9A patent/CN111135450A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP7464465B2 (en) | 2020-06-29 | 2024-04-09 | 花王株式会社 | Micro hollow protrusion tool |
| CN112410867A (en) * | 2020-11-05 | 2021-02-26 | 中国航发北京航空材料研究院 | Processing method of high-temperature alloy close-packed hole column array structure |
| CN112410867B (en) * | 2020-11-05 | 2023-10-20 | 中国航发北京航空材料研究院 | Processing method of high-temperature alloy closely-arranged hole column array structure |
| CN112779516A (en) * | 2020-12-22 | 2021-05-11 | 苏州恒之清生物科技有限公司 | Crystalline silicon microneedle with hard coating protection and preparation method thereof |
| CN112779516B (en) * | 2020-12-22 | 2024-03-08 | 苏州恒之清生物科技有限公司 | Crystal silicon microneedle with hard coating protection and preparation method thereof |
| CN112807561A (en) * | 2021-01-26 | 2021-05-18 | 上海烨映微电子科技股份有限公司 | Microneedle structure and method for producing same |
| CN113443603A (en) * | 2021-06-30 | 2021-09-28 | 苏州恒之清生物科技有限公司 | Preparation method of superfine hollow microneedle chip |
| CN114849051A (en) * | 2022-04-02 | 2022-08-05 | 相邦(苏州)生物材料科技有限公司 | Preparation method of silicon-based microneedle |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111135450A (en) | Microneedle with boss structure and preparation method thereof | |
| US8708966B2 (en) | Microneedle devices and methods of manufacture and use thereof | |
| AU767122B2 (en) | Microneedle devices and methods of manufacture and use thereof | |
| US8043250B2 (en) | High-aspect-ratio microdevices and methods for transdermal delivery and sampling of active substances | |
| US6558361B1 (en) | Systems and methods for the transport of fluids through a biological barrier and production techniques for such systems | |
| US20110177297A1 (en) | Method of manufacturing solid microstructure and solid microstructure manufactured based on same | |
| CN100355470C (en) | Minisize solid silicon needle array chip and its preparation method and use | |
| JP2010502268A (en) | High aspect ratio microdevice and method for transdermal delivery and sampling of active agents | |
| CN105217565B (en) | Manufacturing method of single crystal silicon hollow micro-needle structure | |
| US20210395078A1 (en) | Preparation Method Of Miniature Solid Silicon Needle | |
| KR20030060922A (en) | Transdermal drug delivery devices having coated microprotrusions | |
| CN101342404A (en) | Method for manufacturing different-plane metal hollow fine needle for transdermal drug administration | |
| CN100998901A (en) | Porous silicon painless injection mironeedle array and its preparation method | |
| CN106730309A (en) | A kind of silicon micropin substrate and preparation method thereof | |
| CN100402107C (en) | Metal micro needles array chip and preparation method, and usage | |
| CN110025883A (en) | Metal drug storage microneedle patch and preparation method thereof | |
| JP2008079919A (en) | Needle body and method for producing needle body | |
| CN111729189B (en) | Silicon-based patch and preparation method thereof | |
| CN108751120B (en) | Preparation method of silicon-based microneedle array patch | |
| CN104587567B (en) | A kind of preparation method of micro hollow silicon needle | |
| CN110279935B (en) | Prismatic silicon microneedle and preparation method thereof | |
| CN105903121A (en) | High-density hollow micro-needle array based on negative photoresist and manufacturing technology thereof | |
| CN112807561A (en) | Microneedle structure and method for producing same | |
| CN114010934A (en) | Local porous silicon micro-needle array and preparation method thereof | |
| AU2004200303B2 (en) | Microneedle devices and methods of manufacture and use thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information |
Address after: 201315 5a, building C5, 2555 xiupu Road, Pudong New Area, Shanghai Applicant after: Shanghai sustained release Biotechnology Co.,Ltd. Address before: 201315 5a, building C5, 2555 xiupu Road, Pudong New Area, Shanghai Applicant before: Shanghai slow release new material technology Co.,Ltd. |
|
| CB02 | Change of applicant information |