CN110787361A - Hollow inclined metal microneedle array and manufacturing method thereof based on SU-8 mold - Google Patents
Hollow inclined metal microneedle array and manufacturing method thereof based on SU-8 mold Download PDFInfo
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- 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
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- 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
- C23C14/00—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material
- C23C14/06—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material characterised by the coating material
- C23C14/14—Metallic material, boron or silicon
- C23C14/18—Metallic material, boron or silicon on other inorganic substrates
- C23C14/185—Metallic material, boron or silicon on other inorganic substrates by cathodic sputtering
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- 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
- C23C28/00—Coating for obtaining at least two superposed coatings either by methods not provided for in a single one of groups C23C2/00 - C23C26/00 or by combinations of methods provided for in subclasses C23C and C25C or C25D
- C23C28/02—Coating for obtaining at least two superposed coatings either by methods not provided for in a single one of groups C23C2/00 - C23C26/00 or by combinations of methods provided for in subclasses C23C and C25C or C25D only coatings only including layers of metallic material
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- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
- C25D7/00—Electroplating characterised by the article coated
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- 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
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- 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
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- 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
Abstract
The invention discloses a hollow inclined metal microneedle array and a manufacturing method thereof based on an SU-8 mold, and belongs to the field of micro-nano manufacturing processes. In the micro-needle array, the metal material is electroplatable metal, the hollow inclined metal micro-needle is in an inclined conical shape, and the inclination angle is 50-70 degrees; the vertical height is 500-650 mu m; the hollow inclined metal micro-needle has a structure with the same wall thickness from the bottom to the tip, and the wall thickness is 8-10 mu m; the outer diameter of the bottom of the hollow inclined metal micro-needle is 150-250 μm; the taper angle of the hollow inclined metal micro-needle is 10-15 degrees, and the top of the hollow inclined metal micro-needle is provided with a tip. According to the invention, the SU-8 mold mask pattern is transferred onto the glass sheet, so that the problem of air gaps existing in the traditional contact exposure is avoided, the ultraviolet light intensity reaching each layer of photoresist is improved, and the bonding force between the microneedle mold and the substrate is stronger. The OmniCoat is fully utilized, the adhesion between the SU-8 mould and the glass sheet is improved, and the SU-8 mould is easier to remove at the later stage of the process. The inclined truncated cone-shaped micro-needle obtains a tip end through RIE etching, and the tip end structure of the metal micro-needle is realized.
Description
Technical Field
The invention belongs to the field of micro-nano manufacturing technology, and particularly relates to a hollow inclined metal microneedle array and a manufacturing method based on an SU-8 mold.
Background
The micro-needle subcutaneous injection is an important development direction in the medical field, and the micro-needle with the micron scale can greatly reduce the pain of injection and the fear of needle injection, thereby bringing great convenience for slow injection and quantitative drug injection. Microneedles, typically 100 to 1000 μm in length, penetrate the outer stratum corneum layer of the skin and directly inject therapeutic material into the tissue layer. The penetration depth can be ensured by controlling the length of the microneedles without affecting most nerve fibers and blood vessels located in the dermis layer. The existing microneedles mainly comprise solid microneedles, hollow microneedles, dissolvable microneedles, hydrogel microneedles and the like. The solid micro-needle realizes the drug injection by coating the drug on the surface of the micro-needle or attaching the drug after pulling out the micro-needle. The dissolvable microneedle and hydrogel micro-needle have extremely high requirements on materials of the microneedle, and the strength of the materials is difficult to control; hollow microneedles are more suitable for slow and sustained injection and can deliver different types of pharmaceutical formulations such as solutions, suspensions, emulsions, dry powders and gels.
The micro-manufactured hollow micro-needle can realize the control of the injection speed and the dosage of the drug. In addition, hollow microneedles can not only provide therapy, but can also extract biological fluids from the skin for analysis, monitoring, and bioresponse functions. The hollow microneedle needs to pierce the skin and enter the subcutaneous tissue to realize drug release, so the head structure and strength of the microneedle have important influence on the use of the microneedle.
Currently, hollow microneedles are mainly classified into two types, polymer microneedles and metal microneedles. H HUANG et al, 2007 produced oblique hollow hetero-planar microneedle arrays using the back exposure technique (Huang H, Fu C. differential fabrication methods of out-of-plane polymer hollow new arrays and the irvariations. journal of micro-mechanics and micro-engineering, 2007). The method prepares the polymer micro-needle with sharp corners by utilizing Fresnel diffraction effect and multi-mask simultaneous exposure. In 2007, Kabseog Kim et al produced a vertical truncated SU-8 mold by using back exposure and fresnel diffraction effect, and produced a hollow metal microneedle structure by using the mold and plating process (Kim K, Lee J b. high aspect ratio porous metal microneedle arrays with microfluidic interconnects. microsystem Technologies, 2007). Analyzing the current hollow microneedle preparation process can find that: the hollow microneedle array with the tip is easy to realize by using the polymer material, but the strength of the polymer microneedle is not high; the metallic micro-needle can be prepared by using an SU-8 mold method, but the top tip is difficult to realize, and the SU-8 mold is difficult to remove in a later demolding process, so that the application of the method is greatly limited.
Disclosure of Invention
Aiming at the defects or improvement requirements of the prior art, the invention provides a manufacturing method of a hollow inclined metal microneedle array based on an SU-8 mould, overcomes the defects that the SU-8 mould is difficult to remove and the tip end of a microneedle is difficult to realize in the conventional preparation of the hollow metal microneedle by using the SU-8 mould, and has the advantages of good structural consistency, strong adhesion between the microneedle mould and a substrate and the like.
The hollow inclined metal microneedle array provided by the invention is made of electroplatable metal, the hollow inclined metal microneedle is in an inclined conical shape, and the inclination angle is 50-70 degrees; the vertical height is 500-650 mu m; the hollow inclined metal micro-needle has a structure with the same wall thickness from the bottom to the tip, and the wall thickness is 8-10 mu m; the outer diameter of the bottom of the hollow inclined metal micro-needle is 150-250 μm; the taper angle of the hollow inclined metal micro-needle is 10-15 degrees, and the top of the hollow inclined metal micro-needle is provided with a tip.
The invention provides a manufacturing method of a hollow inclined metal microneedle array based on an SU-8 mould, which mainly comprises micro-processing technologies such as photoetching, electroplating, sputtering and the like, wherein a metal layer electroplated on the surface of the SU-8 mould is etched at the top of the metal layer, and the SU-8 mould is removed, and the specific manufacturing method comprises the following steps:
the method comprises the following steps: preparing an SU-8 mold on a glass substrate comprising the following substeps:
1.1 preparation of SU-8 mold mask pattern on glass substrate
Fully baking or cleaning the glass sheet 1 with the thickness of 500-1000 μm by oxygen plasma to remove organic matters on the surface of the substrate; then sputtering a layer of metal chromium on the surface of the glass sheet; and spin-coating positive photoresist on the chromium metal layer, exposing and developing to expose chromium to be corroded, and corroding in a metal chromium corrosion solution to obtain the SU-8 mold mask pattern layer 4.
1.2 preparing SU-8 mould bottom sacrificial layer on the surface of glass sheet
And (3) cleaning and fully baking the sample piece, and spin-coating Omnicoat on the side of the sample piece without the metal chromium as the SU-8 mold bottom sacrificial layer 2 and fully baking. OmniCoat is used as a special tackifying/degumming auxiliary agent for SU-8, is beneficial to enhancing the adhesiveness of the SU-8 mould and a glass substrate and is beneficial to removing cured SU-8.
1.3 Back side oblique Exposure
Spin-coating a first layer of SU-8 photoresist 3 on the Omnicoat surface of the sample obtained in step 1.2, wherein the thickness is 1-2 μm, then performing vertical maskless exposure on the front surface (fig. 2a), spin-coating a second layer of SU-8 photoresist 5 on the same surface, wherein the thickness is 500-650 μm, the thickness of the second layer of photoresist 5 determines the vertical height of the microneedle on the SU-8 mold and the vertical height H of the hollow inclined metal microneedle, after fully baking the second layer of photoresist layer 5, placing the sample under an ultraviolet exposure lamp, enabling the SU-8 mold mask pattern layer 4 to face the ultraviolet lamp, enabling the included angle β between the sample and the ultraviolet light to be 40-90 degrees by using a clamp (fig. 2c), determining the inclined angle of the microneedle on the SU-8 mold and the inclined metal inclined angle α by using the sample and the ultraviolet light included angle β, and then baking and developing to obtain the SU-8 mold 6.
Because the refractive indexes of ultraviolet light in different media are different, the inclination angle of the microneedle on the SU-8 mould is mainly determined by the incident angle, the refraction coefficients of the SU-8 photoresist and the incident medium, and when the microneedle is exposed in an air medium in an inclined mode, the inclination angle of the microneedle on the SU-8 mould is 54-90 degrees. Because the refractive indexes of ultraviolet rays in the glycerol and the SU-8 photoresist are close, when back surface inclined exposure is carried out in a glycerol medium, the inclination angle of the microneedle on the SU-8 mould is 19-90 degrees. Therefore, when preparing a microneedle mold with an inclination angle smaller than 54 °, the sample is immersed in a glycerol medium and then subjected to back side oblique exposure (fig. 2 d).
And (3) spraying a layer of OmniCoat on the surface of the obtained SU-8 mould by using a glue sprayer, and then placing the mould in a constant temperature box for hot drying. The OmniCoat function of the surface of the SU-8 mould microneedle is the same as that of the sacrificial layer at the bottom of the SU-8 mould structure in the step (1.2), and the solidified SU-8 is removed conveniently.
In back exposure, the photoresist in contact with the glass sheet can fully absorb ultraviolet light, which is beneficial to improving the adhesion of the SU-8 mold and the glass substrate; the Fresnel diffraction in photoetching is enhanced due to the distance between the chromium pattern layer on the glass sheet and the bottom of the photoresist, the SU-8 glue layer which is in contact with the glass sheet in exposure faces outwards, the ultraviolet light distribution diameter is sharply shrunk, the ultraviolet light intensity is rapidly reduced, and finally the microneedle on the SU-8 mould is in an inclined truncated cone shape; the SU-8 mold mask graph is copied onto the glass sheet, so that an air gap between the mask and the glass sheet in contact exposure is eliminated, and the consistency of the SU-8 mold is improved.
Step two: preparing hollow inclined metal microneedles on the surface of the SU-8 mould; the method comprises the following substeps:
2.1 sputtering and depositing a metal seed layer on the surface of the SU-8 mould
And (3) sputtering and depositing a metal seed layer 7 on the SU-8 mould 6 sprayed with OmniCoat obtained in the step (1.3), wherein the thickness is 100-200 nm, and the microneedle on the mould, which is formed by the sample piece and the metal deposition direction at an included angle of 180- α -8, is parallel to the metal deposition direction in the sputtering process (figure 2e), so that the exterior of the microneedle on the SU-8 mould is completely wrapped by the deposited metal seed layer 7.
2.2 electroplating a metal layer on the surface of the metal seed layer to form an inclined metal micro-needle structure layer
And putting the sample piece into an electrolyte solution capable of plating metal for electroplating, wherein the thickness of the electroplated metal layer is 8-10 mu m, and an inclined metal micro-needle structure layer 8 is formed (figure 2 f).
Step three: preparing an inclined metallic microneedle tip comprising the following sub-steps:
3.1 preparation of tilted Metal microneedle tip mask on SU-8 mold
Coating SU-8 photoresist on the surface of the inclined metal microneedle structure layer 8 obtained in the step 2.2, then placing the inclined metal microneedle structure layer on a hot plate for baking to ensure that an SU-8 adhesive layer is sufficiently flat, then placing the sample under a microscope to observe the vertical distance d between the SU-8 photoresist surface and the top of the SU-8 mould microneedle, and repeating the spin coating and the baking until the vertical distance d between the SU-8 photoresist surface and the top of the SU-8 mould microneedle is 50-70 micrometers (fig. 2 g).
And (3) placing the gluing surface of the sample piece under an ultraviolet lamp for maskless vertical exposure, wherein the exposure amount is 1/4-1/3 of standard exposure energy, and then carrying out normal hot baking to obtain the tip mask 9 with the inclined top of the microneedle on the SU-8 mould. The temperature tolerance of the photoresist is improved after exposure, and insufficient exposure is beneficial to removing the microneedle top inclined tip mask 9 on the SU-8 mould.
3.2 preparation of inclined tips at tops of inclined metallic microneedles in SU-8 molds
Performing first RIE etching on the sample piece treated in the step 3.1, wherein the etching power is 80-120W, and the oxygen flow is 10cm3/min～40cm3And/min, the oxygen pressure is 0.5Pa to 15Pa, the included angle gamma between the sample piece and the etching direction is 60-70 degrees during etching, and the solidified SU-8 glue layer at the top of the inclined metal micro-needle structure layer 8 is etched.
Keeping the angle between the sample and the etching direction constant, and placing the sample in a fluorine-containing gas (such as CF)4，O2) And (5) performing second RIE etching to remove the inclined metal microneedle structure layer and the electroplated metal layer on the top surface of the microneedle on the SU-8 mould until the SU-8 mould is exposed (fig. 2 h). Because the microneedles on the SU-8 mold are all inclined truncated cones, in the second RIE etching, the inclined metal microneedle structure layer right below the tops of the microneedles on the SU-8 mold is shielded and cannot be etched, and finally a tip structure is formed (fig. 2 h). The included angle gamma between the sample piece and the etching direction can increase the area of shielding metal and adjust the appearance of the tip of the micro-needle.
Step four: removing SU-8 mould
And (3) placing the sample piece obtained in the step (3) into a special degumming solution for SU-8, carrying out ultrasonic development for 30-50 min, carrying out ultrasonic power for 30-50W, and carrying out temperature of 50-80 ℃ to obtain a hollow inclined metal microneedle array diagram (2i) with a tip.
Compared with the prior art, the technical scheme of the invention can make the following obvious progress.
1) The SU-8 mold mask pattern is transferred to the glass sheet, so that the problem of air gaps in the traditional contact exposure is avoided, the ultraviolet light intensity reaching each layer of photoresist is improved, and the bonding force between the microneedle mold and the substrate is stronger.
2) The invention fully utilizes OmniCoat, improves the adhesion of the SU-8 mould and the glass sheet, and simultaneously, the SU-8 mould is easier to remove at the later stage of the process.
3) The inclined truncated cone-shaped micro-needle obtains a tip end through RIE etching, and the tip end structure of the metal micro-needle is realized.
The technical solutions of the present invention are further described below with reference to the following examples and drawings, but the technical solutions of the present invention are not limited thereto.
Drawings
FIG. 1: schematic diagram of hollow oblique metal microneedle array
FIG. 2 a: SU-8 mold bottom sacrificial layer, SU-8 mold mask pattern layer, first SU-8 photoresist distribution on glass sheet, and first SU-8 photoresist front exposure schematic diagram
FIG. 2 b: schematic diagram of second layer of SU-8 photoresist
FIG. 2 c: schematic diagram of SU-8 mold prepared by back inclined exposure
FIG. 2 d: schematic diagram of SU-8 mold prepared by oblique exposure of back surface in glycerol
FIG. 2 e: schematic diagram of sputtering deposition of metal seed layer
FIG. 2 f: schematic diagram of electroplated metal layer
FIG. 2 g: schematic diagram of microneedle top oblique tip mask on preparation SU-8 mold
FIG. 2 h: schematic diagram of top inclined tip of microneedle on preparation SU-8 mold
FIG. 2 i: section schematic diagram of hollow inclined metal microneedle array with tip
Reference numerals:
1. glass sheet, 2, a sacrificial layer (a structure in front) at the bottom of an SU-8 mould, 3, a first layer of SU-8 photoresist, 4, a mask graph layer of the SU-8 mould, 5, a second layer of SU-8 photoresist, 6, an SU-8 mould, 7, a metal seed layer, 8, an inclined metal microneedle structure layer, 9, an inclined tip mask at the top of a microneedle on the SU-8 mould, d, the vertical distance between the surface of the SU-8 photoresist and the top of the SU-8 mould, H, the vertical height of a hollow inclined metal microneedle, α, the inclination angle of the microneedle on the SU-8 mould and the inclination angle of the hollow inclined metal microneedle, β, the included angle between a sample piece and ultraviolet light, 180- α, and the included angle between the sample piece and the metal deposition direction
Angle between etching direction and sample
Detailed Description
The invention is further described with reference to specific examples.
Example 1
Referring to fig. 2, the hollow oblique metal microneedle array of this embodiment has a microneedle vertical height H of 500 μm, a microneedle bottom outer diameter of 150 μm, a microneedle oblique angle α of 70 °, a plated metal layer of nickel, a microneedle wall thickness of 8 μm, and a microneedle taper angle of 10 °.
The hollow oblique metal microneedle array of this example was prepared as follows:
the method comprises the following steps: preparing an SU-8 mold on a glass substrate comprising the following substeps:
1.1 preparation of SU-8 mold mask pattern on glass substrate
1, cleaning a quartz glass sheet with the thickness of 500 mu m by oxygen plasma; then sputtering a layer of 60nm metal chromium on the surface of the quartz glass sheet; and spin-coating positive photoresist on the chromium metal layer, exposing and developing to expose chromium to be corroded, and corroding in a metal chromium corrosion solution to obtain the SU-8 mold mask pattern layer 4.
1.2 preparing SU-8 mould bottom sacrificial layer on the surface of glass sheet
And cleaning and fully baking the sample piece, spin-coating 3nm Omnicoat on one surface of the sample piece without the metal chromium as the SU-8 mold bottom sacrificial layer 2, and fully baking.
1.3 Back side oblique Exposure
Spin-coating a first layer of SU-8 photoresist 3 with the thickness of 1 μm on the OmniCoat surface of the step 1.2, then performing vertical maskless exposure on the front surface (figure 2a) with the exposure dose of 70mJ/cm2, spin-coating a second layer of SU-8 photoresist 5 with the thickness of 500 μm on the same surface, after the second layer of SU-8 photoresist 5 is fully prebaked, placing the sample under an ultraviolet exposure lamp, enabling the SU-8 mold mask pattern layer 4 to face the ultraviolet lamp, enabling the sample to form an included angle β of 55 degrees with the ultraviolet light by using a clamp (figure 2c) and the exposure dose of 200mJ/cm2, and obtaining the SU-8 mold 6 through postbaking and developing.
A layer of OmniCoat is sprayed on the surface of the SU-8 mould 6 by a glue sprayer, the mould is placed on a spin coater to spin glue at the speed of 3000 r/min, and then the mould is placed in a constant temperature box to be heated and dried for 1 minute at the temperature of 200 ℃.
Step two: preparing hollow inclined metal microneedles on the surface of an SU-8 mould, wherein the method comprises the following substeps:
2.1 sputtering and depositing a metal seed layer on the surface of the SU-8 mould
And (3) sputtering and depositing a metal seed layer 7 on the SU-8 mould 6 of the sample obtained in the step (1.3), wherein the thickness is 100nm, the included angle between the sample and the metal deposition direction is 110 degrees in sputtering, the microneedle on the SU-8 mould is parallel to the metal deposition direction (figure 2e), and the exterior of the microneedle on the SU-8 mould is completely wrapped by the deposited metal seed layer 7.
2.2 electroplating a metal layer on the surface of the metal seed layer to form an inclined metal micro-needle structure layer
And putting the sample piece into an electrolyte solution of metallic nickel for electroplating, wherein the thickness of the electroplated metal layer is 8 mu m, and an inclined metallic micro-needle structure layer 8 is formed (figure 2 f).
Step three: preparing an inclined metallic microneedle tip comprising the following sub-steps:
3.1 preparation of tilted Metal microneedle tip mask on SU-8 mold
Coating SU-8 photoresist on the surface of the inclined metal microneedle structure layer 8 of the sample obtained in the step 2.2, then placing the sample on a hot plate for baking to ensure that an SU-8 adhesive layer is sufficiently flat, then placing the sample under a microscope to observe the vertical distance d between the SU-8 photoresist surface and the top of the SU-8 mold microneedle, and repeating the spin coating and the baking until the vertical distance between the SU-8 photoresist surface and the top of the SU-8 mold microneedle is 50 micrometers (fig. 2 g).
And (3) placing the gluing surface of the sample piece under an ultraviolet lamp for maskless vertical exposure with the exposure amount of 200mJ/cm2, and then performing normal heat baking to obtain the inclined metal microneedle top tip mask 9.
3.2 preparation of inclined tips at tops of inclined metallic microneedles in SU-8 molds
Carrying out first RIE etching on the sample piece treated in the step 3.1, wherein the etching power is 80W, and the oxygen flow isMeasuring 10cm3And/min, the oxygen pressure is 0.5Pa, the included angle gamma between the sample piece and the etching direction in the etching process is 60 degrees, and the solidified SU-8 glue layer at the top of the inclined metal microneedle structure layer 8 is etched.
Keeping the included angle between the sample piece and the etching direction unchanged, placing the sample piece in fluorine-containing gas (CF4, O2) for second RIE etching, and removing the inclined metal microneedle structure layer and the electroplated metal layer on the top surface of the microneedle on the SU-8 mold until the SU-8 mold is exposed (FIG. 2 h).
SU-8 mould is got rid of to 4
And (3) placing the sample obtained in the step (3) into a special degumming solution for SU-8, carrying out ultrasonic development for 30min at an ultrasonic power of 30W and a temperature of 50 ℃ to obtain the hollow inclined metal microneedle array with the tip (figure 2 i).
Example 2
Referring to fig. 2, the hollow oblique metal microneedle array of this embodiment has a microneedle vertical height H of 650 μm, a microneedle bottom outer diameter of 250 μm, a microneedle oblique angle α of 50 °, a plated metal layer of nickel, a microneedle wall thickness of 10 μm, and a microneedle taper angle of 15 °.
The hollow oblique metal microneedle array of this example was prepared as follows:
the method comprises the following steps: preparation of SU-8 molds on glass substrates
The method comprises the following substeps:
1.1 preparation of SU-8 mold mask pattern on glass substrate
1, cleaning a quartz glass sheet with the thickness of 1000 mu m by oxygen plasma; then sputtering a layer of 60nm metal chromium on the surface of the quartz glass sheet; and spin-coating positive photoresist on the chromium metal layer, exposing and developing to expose chromium to be corroded, and corroding in a metal chromium corrosion solution to obtain the SU-8 mold mask pattern layer 4.
1.2 preparing SU-8 mould bottom sacrificial layer on the surface of glass sheet
And cleaning and fully baking the sample piece, spin-coating 3nm Omnicoat on one surface of the sample piece without the metal chromium as the SU-8 mold bottom sacrificial layer 2, and fully baking.
1.3 Back side oblique Exposure
A first layer of SU-8 photoresist 3 is spin-coated on the Omnicoat surface of step 1.2 to a thickness of2 μm, then subjected to a front vertical maskless exposure (FIG. 2a) at an exposure dose of 80mJ/cm2Spin coating a second layer of SU-8 photoresist 5 on the same surface, wherein the thickness of the second layer of SU-8 photoresist 5 is 650 μm, fixing the sample in a quartz glass container, placing the quartz glass container under an ultraviolet exposure lamp, allowing the SU-8 mold mask pattern layer 4 to face the ultraviolet lamp, making the included angle between the sample and the ultraviolet lamp β be 48 degrees by using a clamp (see figure 2d), adding glycerol into the quartz glass container until the glycerol immerses the whole sample, and exposing after the glycerol liquid level is static, wherein the exposure dose is 300mJ/cm2. And baking and developing to obtain the SU-8 mold.
And (3) spraying a layer of OmniCoat on the surface of the SU-8 mould by using a glue sprayer, spinning at a high speed of 3000 rpm on a spin coater, and then placing the mould in a thermostat for 1 minute at 200 ℃.
Step two: preparing hollow inclined metal microneedles on the surface of an SU-8 mould, wherein the method comprises the following substeps:
2.1 sputtering and depositing a metal seed layer on the surface of the SU-8 mould
And (3) sputtering and depositing a metal seed layer 7 on the SU-8 mould 6 of the sample obtained in the step (1.3), wherein the thickness is 200nm, the included angle between the sample and the metal deposition direction is 130 degrees in sputtering, the microneedle on the SU-8 mould is parallel to the metal deposition direction (figure 2e), and the exterior of the microneedle on the SU-8 mould is completely wrapped by the deposited metal seed layer 7.
2.2 electroplating a metal layer on the surface of the metal seed layer to form an inclined metal micro-needle structure layer
And putting the sample piece into an electrolyte solution of metallic nickel for electroplating, wherein the thickness of the electroplated metal layer is 10 mu m, and forming the inclined metallic micro-needle structure layer 8.
Step three: preparing an inclined metallic microneedle tip comprising the following sub-steps:
3.1 preparation of tilted Metal microneedle tip mask on SU-8 mold
And (3) coating SU-8 photoresist on the surface of the inclined metal microneedle structure layer 8 of the sample obtained in the step 2.2, then placing the sample on a hot plate for hot baking to ensure that an SU-8 adhesive layer is sufficiently flat, then placing the sample under a microscope to observe the vertical distance d between the SU-8 photoresist surface and the top of the SU-8 mold microneedle, and repeating the spin coating and the hot baking until the vertical distance d between the SU-8 photoresist surface and the top of the SU-8 mold microneedle is 70 micrometers.
Placing the sample piece adhesive surface under an ultraviolet lamp for maskless vertical exposure with exposure of 220mJ/cm2And then normal thermal baking is performed to obtain the tilted metallic microneedle top tip mask 9.
3.2 preparation of inclined tips at tops of inclined metallic microneedles in SU-8 molds
Carrying out first RIE etching on the sample piece processed in the step 3.1, wherein the etching power is 120W, and the oxygen flow is 40cm3And/min, the oxygen pressure is 15Pa, the included angle gamma between the sample piece and the etching direction in the etching process is 70 degrees, and the solidified SU-8 glue layer at the top of the inclined metal micro-needle structure layer 8 is etched.
Keeping the included angle between the sample piece and the etching direction unchanged, placing the sample piece in fluorine-containing gas (CF4, O2) for second RIE etching, and removing the inclined metal microneedle structure layer and the electroplated metal layer on the top surface of the microneedle on the SU-8 mold until the SU-8 mold is exposed (FIG. 2 h).
4. Removing SU-8 mould
And (3) placing the sample obtained in the step (3) into a special degumming solution for SU-8, carrying out ultrasonic development for 50 minutes at an ultrasonic power of 50W and a temperature of 80 ℃ to obtain the hollow inclined metal microneedle array with the tip (see figure 2 i).
Claims (2)
1. A hollow inclined metal microneedle array is characterized in that a metal material is electroplatable metal, hollow inclined metal microneedles are in an inclined conical shape, and the inclination angle is 50-70 degrees; the vertical height is 500-650 mu m; the hollow inclined metal micro-needle has a structure with the same wall thickness from the bottom to the tip, and the wall thickness is 8-10 mu m; the outer diameter of the bottom of the hollow inclined metal micro-needle is 150-250 μm; the taper angle of the hollow inclined metal micro-needle is 10-15 degrees, and the top of the hollow inclined metal micro-needle is provided with a tip.
2. The method of manufacturing a hollow oblique metallic microneedle array as claimed in claim, comprising the steps of:
the method comprises the following steps: preparing an SU-8 mold on a glass substrate comprising the following substeps:
1.1 preparation of SU-8 mold mask pattern on glass substrate
Fully baking the glass sheet 1 by heat or cleaning the glass sheet by oxygen plasma to remove organic matters on the surface of the substrate; then sputtering a layer of metal chromium on the surface of the glass sheet; spin-coating positive photoresist on the chromium metal layer, exposing and developing to expose chromium to be corroded, and corroding in a metal chromium corrosion solution to obtain an SU-8 mold mask pattern layer 4;
1.2 preparing SU-8 mould bottom sacrificial layer on the surface of glass sheet
Cleaning and fully baking the sample piece, spin-coating Omnicoat on one surface of the sample piece without metal chromium as a SU-8 mold bottom sacrificial layer 2, and fully baking;
1.3 Back side oblique Exposure
Spin-coating a first layer of SU-8 photoresist 3 on the Omnicoat surface of the sample obtained in the step 1.2, and then performing vertical maskless exposure on the front surface, spin-coating a second layer of SU-8 photoresist 5 on the same surface, wherein the thickness of the second layer of photoresist 5 determines the vertical height of the microneedle on the SU-8 mold and the vertical height H of the hollow inclined metal microneedle, after the second layer of photoresist 5 is fully prebaked, placing the sample under an ultraviolet exposure lamp, enabling the mask pattern layer 4 of the SU-8 mold to face the ultraviolet lamp, making an included angle β between the sample and the ultraviolet light be 40-90 degrees by using a clamp, making an included angle β between the sample and the ultraviolet light determine the inclined angle α of the microneedle on the SU-8 mold, and then obtaining the SU-8 mold 6 through postbaking and developing;
spraying a layer of OmniCoat on the surface of the obtained SU-8 mould by using a glue sprayer, putting the mould on a spin coater for spin coating, and then putting the mould in a constant temperature box for hot drying;
step two: preparing hollow inclined metal microneedles on the surface of the SU-8 mould; the method comprises the following substeps:
2.1 sputtering and depositing a metal seed layer on the surface of the SU-8 mould
Sputtering and depositing a metal seed layer 7 on the SU-8 mould 6 sprayed with Omnicoat obtained in the step 1.3, wherein the included angle between the sample piece and the metal deposition direction is 180- α -8, and the microneedle on the mould is parallel to the metal deposition direction, so that the exterior of the microneedle on the SU-8 mould is completely wrapped by the deposited metal seed layer 7;
2.2 electroplating a metal layer on the surface of the metal seed layer to form an inclined metal micro-needle structure layer
Putting the sample piece into an electrolyte solution capable of plating metal for electroplating to form an inclined metal microneedle structure layer 8;
step three: preparing an inclined metallic microneedle tip comprising the following sub-steps:
3.1 preparation of tilted Metal microneedle tip mask on SU-8 mold
And (3) coating SU-8 photoresist on the surface of the inclined metal microneedle structure layer 8 obtained in the step 2.2, then placing the inclined metal microneedle structure layer on a hot plate for baking to ensure that an SU-8 adhesive layer is fully flat, then placing the sample under a microscope to observe the vertical distance d between the SU-8 photoresist surface and the top of the SU-8 mould microneedle, and repeating the spin coating and the baking until the vertical distance d between the SU-8 photoresist surface and the top of the SU-8 mould microneedle is 50-70 micrometers.
Placing the gluing surface of the sample piece under an ultraviolet lamp for maskless vertical exposure with the exposure amount being 1/4-1/3 of standard exposure energy, and then performing normal hot baking to obtain a microneedle top inclined tip mask 9 on the SU-8 mold;
3.2 preparation of inclined tips at tops of inclined metallic microneedles in SU-8 molds
Carrying out first RIE etching on the sample piece treated in the step 3.1, wherein the included angle gamma between the sample piece and the etching direction in the etching is 60-70 degrees, and etching off the solidified SU-8 adhesive layer at the top of the inclined metal microneedle structure layer 8;
keeping an included angle between the sample piece and the etching direction unchanged, placing the sample piece in fluorine-containing gas for second RIE etching, and removing the inclined metal microneedle structure layer and the electroplated metal layer on the top surface of the microneedle on the SU-8 mold until the SU-8 mold is exposed;
step four: removing the SU-8 mold;
and (4) placing the sample piece obtained in the step (3) into a special degumming solution for SU-8 to obtain the hollow inclined metal microneedle array with the tip.
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