CN111331871A - Mold surface treatment method and microneedle fabrication method - Google Patents

Abstract

A mold surface treatment method for improving the demoulding effect of microneedles, comprising: cleaning a master mold with a microporous structure; using oxygen plasma to activate the cleaned master mold; A seed layer and a film layer are sequentially deposited on the surface of the master mold, wherein the film layer is used to reduce the free energy of the surface of the master mold. The method can promote the penetration and filling of the microporous structure of the polymer material, and the deposition of the Au film layer on the surface of the mold can greatly reduce the surface free energy of the mold, effectively solve the problem of adhesion between the polymer and the mold during the demolding process, and improve the processing efficiency of polymer microneedles And the success rate, prolong the service life of the mold. Due to its good biocompatibility, Au does not produce toxic, harmful or dangerous chemical components during processing, which is suitable for life science-related research and can meet the needs of mass production. And the whole process adopts low temperature process, which will not cause thermal damage to the master mold.

Description

Mold surface treatment method and microneedle fabrication method

technical field

The present disclosure relates to the technical field of micro-nano processing, and in particular, to a mold surface treatment method and a micro-needle fabrication method.

Background technique

Microneedle is a functional micro-nano structure composed of many micron needle-like protrusions, and is mostly used in skin moisturizing, transdermal drug delivery, painless immunotherapy and other cosmetic medicine fields. Among them, the microneedle structure of polymer materials (such as hyaluronic acid HA, polyvinyl alcohol PVA, polylactic acid PLA, etc.) has received extensive attention due to its good biocompatibility, flexibility, and efficient drug loading.

The production method of polymer microneedle structure generally requires a master mold (the material is usually polydimethylsiloxane PDMS or plexiglass PMMA, etc.) as a negative mold, on which many micropores are processed, and then cast polymerization on it. After curing and molding, demoulding and separation are carried out to obtain a microneedle protruding structure complementary to the micropore shape of the negative mold.

However, in the case of high density, small size or large overall area of microneedles, it may be difficult for the polymer to enter the inside of the micropores during the casting process, resulting in the inability to form microneedle protruding structures complementary to the shape of the micropores, or due to polymerization The contact area between the object and the master mold is large, and the adhesion phenomenon occurs during demolding, which leads to problems such as difficulty in demolding, damage and deformation of the microneedle structure after demolding, and residual polymer in the micropores of the master mold. This seriously affects the processing efficiency, yield, and service life of the master mold for the polymer microneedle structure.

In order to improve the above-mentioned problems, the method of coating or depositing a fluoropolymer film or a long-chain silane anti-adhesion layer on the surface of the mold before casting the polymer is usually adopted. However, for the commonly used master mold materials for microneedles such as PDMS and PMMA, the deposition efficiency and anti-adhesion effect of this anti-adhesive layer are limited, and there may still be problems such as adhesion and difficulty in demolding during demolding. In addition, spin coating or immersion coating has the risk of filling in fine pores. The vapor deposition method is usually cumbersome, and there are toxic, harmful or dangerous chemical components in the processing process, which is not conducive to biocompatibility, and requires special deposition equipment, which is poorly compatible with conventional semiconductor processes. Some vapor deposition methods require heating conditions, which have potential effects on commonly used master mold materials (such as PDMS, etc.), which may cause deformation of the microporous structure, thereby affecting the subsequent casting process. The surface treatment method of simply depositing a fluoropolymer film or a long-chain silane anti-adhesion layer cannot effectively promote the filling of the polymer into the micropores of the mold, and the casted microneedle structure is often damaged and incomplete.

SUMMARY OF THE INVENTION

(1) Technical problems to be solved

In view of the above technical problems, the present disclosure proposes a mold surface treatment method and a microneedle manufacturing method, which are used to at least solve the above technical problems.

(2) Technical solutions

According to a first aspect of the embodiments of the present disclosure, there is provided a mold surface treatment method for improving the demolding effect of microneedles, including: cleaning a master mold with a microporous structure; The activated master mold is activated; a seed layer and a thin film layer are sequentially deposited on the surface of the activated master mold, wherein the thin film layer is used to reduce the free energy of the surface of the master mold.

Optionally, the time range for the activation treatment is 1-10 minutes.

Optionally, a Ti seed layer or a Cr seed layer is deposited on the surface of the activated master mold.

Optionally, the thin film layer is an Au thin film layer, and the thickness of the Au thin film layer ranges from 5 to 200 nanometers.

Optionally, the thickness of the seed layer is in the range of 1-20 nanometers.

Optionally, cleaning the master mold with the microporous structure includes: immersing the master mold with the microporous structure in acetone and isopropyl alcohol solution for ultrasonic cleaning in turn; using nitrogen to clean the master mold after ultrasonic cleaning. The mold is dried.

Optionally, the time range of ultrasonic cleaning is 5-10 minutes.

Optionally, the thickness of the Ti seed layer or the Cr seed layer is 3-5 nm.

Optionally, a magnetron sputtering coating machine, an electron beam evaporation coating machine or a thermal evaporation coating machine is used to sequentially deposit the seed layer and the thin film layer on the surface of the activated master mold.

According to a second aspect of the embodiments of the present disclosure, there is provided a method for fabricating microneedles, characterized by comprising: cleaning a master mold with a microporous structure; using oxygen plasma to activate the cleaned master mold treatment; sequentially depositing a seed layer and an Au film layer on the surface of the activated master mold; casting a high molecular polymer material on the Au film layer, and then demolding and separating after the polymer material is cured and formed to obtain polymer microneedles.

(3) Beneficial effects

The present disclosure provides a mold surface treatment method and a microneedle manufacturing method, and the beneficial effects are as follows:

1. This method performs oxygen plasma activation treatment on the surface of the master mold, which can promote the penetration of polymer materials and fill the microporous structure. The deposition of Au on the mold surface can greatly reduce the surface free energy of the mold, effectively solving the problem of polymer and mold in the demolding process. To solve the adhesion problem, improve the processing efficiency and success rate of polymer microneedles, and prolong the service life of the mold.

2. Due to the good biocompatibility of Au, no toxic, harmful or dangerous chemical components are produced during processing, which is suitable for life science related research.

3. The method is simple to operate, can be realized by using conventional semiconductor processing equipment, has good compatibility with the semiconductor processing process chain, and can meet the needs of mass production. The low temperature process is adopted in the whole process, which will not cause thermal damage to the master mold.

Description of drawings

For a more complete understanding of the present disclosure and its advantages, reference will now be made to the following description taken in conjunction with the accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments consistent with the present disclosure, and Together, the description serves to explain the principles of the present disclosure. in:

FIG. 1 schematically shows a flow chart of a method for processing a mold surface according to an exemplary embodiment of the present disclosure;

FIG. 2 schematically shows a flow chart of a method for fabricating polymer microneedles according to an exemplary embodiment of the present disclosure;

3 shows the microstructure of the hyaluronic acid microneedle array obtained after the surface of the PDMS master mold is treated by the mold surface treatment method according to an exemplary embodiment of the present disclosure, the hyaluronic acid is cast, and the hyaluronic acid microneedle array is obtained after curing, molding and demolding ;

Fig. 4 shows the hyaluronic acid structure microstructure diagram obtained after direct casting of hyaluronic acid without surface treatment of the master mold, and curing, molding and demoulding;

Figure 5 shows the microstructure of the hyaluronic acid microneedle array obtained after the surface of the PDMS master mold is treated with a conventional method (vapor deposition long-chain silane anti-adhesion layer), casting hyaluronic acid, curing, molding and demolding .

Detailed ways

Hereinafter, embodiments of the present disclosure will be described with reference to the accompanying drawings. It should be understood, however, that these descriptions are exemplary only, and are not intended to limit the scope of the present disclosure. In the following detailed description, for convenience of explanation, numerous specific details are set forth in order to provide a thorough understanding of the embodiments of the present disclosure. It will be apparent, however, that one or more embodiments may be practiced without these specific details. Also, in the following description, descriptions of well-known structures and techniques are omitted to avoid unnecessarily obscuring the concepts of the present disclosure.

Embodiments of the present disclosure provide a method for processing a mold surface, the method comprising cleaning a master mold with a microporous structure. The cleaned master mold is activated by oxygen plasma. A seed layer and a thin film are sequentially deposited on the surface of the activated master mold. This method can improve the release effect of polymer microneedles.

FIG. 1 schematically shows a flow chart of a method for processing a mold surface according to an exemplary embodiment of the present disclosure. As shown in FIG. 1 , the method may include, for example, operations S101 to S103.

S101, cleaning the master mold with the microporous structure.

In a feasible way of this embodiment, the master mold with the microporous structure can be immersed in acetone and isopropanol solution for ultrasonic cleaning in sequence, and the time range of ultrasonic cleaning is 5-10 minutes, for example, ultrasonic cleaning can be performed for 5 minutes , which is not limited in this disclosure. The master mold can be, for example, a PDMS template.

After ultrasonic cleaning is complete, the master mold is removed, blown dry with nitrogen, and transferred to a dry environment.

S102, using oxygen plasma to activate the cleaned master mold.

In a feasible way of this embodiment, the cleaned master mold can be put into a device that can generate oxygen plasma, and the oxygen plasma is used for activation treatment, so as to promote the penetration of the polymer material into and fill the microcosms of the master mold. Pore structure. The time range of the activation treatment is 1-10 minutes, for example, it can be activated for 5 minutes, which is not limited in the present disclosure.

In a feasible way of this embodiment, the equipment that can generate oxygen plasma includes but is not limited to reactive ion etching machine RIE, inductively coupled plasma etching machine ICP, plasma degumming machine, etc. with oxygen plasma bombardment function equipment. Preferably, a reactive ion etching machine is used, and the activation treatment time is 5 minutes.

S103 , depositing a seed layer and a thin film layer on the surface of the activated master mold in sequence, wherein the thin film layer is used to reduce the free energy of the surface of the master mold.

In a feasible way of this embodiment, the activated master mold is put into a vacuum coating equipment, and a seed layer and a thin film layer are sequentially deposited to reduce the free energy on the surface of the master mold. Wherein, the thickness of the seed layer may range from 1 to 20 nanometers. The seed layer may be, for example, a Ti seed layer or a Cr seed layer, and the thickness is preferably 3-5 nanometers, which is not limited in the present disclosure. The thin film layer can be an Au thin film layer, and its thickness can be, for example, 5-200 nanometers, and the preferred thickness range is 10-20 nanometers.

In a feasible way of this embodiment, the vacuum coating equipment includes but is not limited to a magnetron sputtering coating machine, an electron beam evaporation coating machine, a thermal evaporation coating machine, etc. Preferably, a magnetron sputtering coating machine is used.

Based on the above-mentioned processing method of the mold surface, an embodiment of the present disclosure further provides a method for manufacturing a polymer microneedle. FIG. 2 schematically shows a flow chart of a method for fabricating polymer microneedles according to an exemplary embodiment of the present disclosure. As shown in FIG. 2 , the method may include, for example, operations S201 to S204.

S201, cleaning the master mold with the microporous structure.

S202, using oxygen plasma to activate the cleaned master mold.

S203, sequentially depositing a seed layer and a thin film layer on the surface of the activated master mold.

S204 , casting a high molecular polymer material on the Au film layer, and performing demolding and separation after the polymer material is cured and formed to obtain polymer microneedles.

In a feasible way of this embodiment, the polymer material can be, for example, hyaluronic acid, which is transferred to a ventilated and dry environment after vacuuming for 1 hour, and then demolded and separated after the hyaluronic acid is cured and formed to obtain hyaluronic acid. Microneedle array structure.

For details that are not described in this embodiment, please refer to the above-mentioned embodiments of the mold surface treatment method, which will not be repeated here.

In the method implemented above, the oxygen plasma activation treatment on the surface of the master mold can promote the penetration of the polymer material and the filling of the microporous structure. The deposition of Au on the mold surface can greatly reduce the free energy of the mold surface and effectively solve the problem of adhesion between the polymer and the mold during the demolding process. And due to the good biocompatibility of Au, no toxic, harmful or dangerous chemical components are produced during processing, which is suitable for life science related research. This surface treatment method uses conventional semiconductor processing equipment, is suitable for mass production, and adopts a low-temperature process, which will not cause thermal damage to the master mold.

The present disclosure also verifies the method provided in this embodiment, and FIG. 3 to FIG. 5 show the surface topography of the microneedles obtained by different methods.

FIG. 3 shows the microstructure of the hyaluronic acid microneedle array obtained after the surface of the PDMS master mold is treated by the mold surface treatment method according to an exemplary embodiment of the present disclosure, casting hyaluronic acid, curing, molding and demolding. picture. Figure 3 shows that the microneedles are intact and the array is complete, indicating that the hyaluronic acid completely filled the microporous structure of the master mold during the casting process, and no adhesion problem occurred during demolding.

FIG. 4 shows the microstructure diagram of the hyaluronic acid structure obtained after direct casting of hyaluronic acid without surface treatment of the master mold, and curing, molding and demoulding. Figure 4 shows that the desired microneedle shape was not formed, and only part of the base of the microneedle remained, indicating that the hyaluronic acid did not fully penetrate and fill the interior of the microporous structure of the master mold during the casting process.

Figure 5 shows the microstructure of the hyaluronic acid microneedle array obtained after the surface of the PDMS master mold is treated with a conventional method (vapor deposition long-chain silane anti-adhesion layer), casting hyaluronic acid, curing, molding and demolding . Figure 5 shows that the microneedle array is incomplete and has many defects, indicating that hyaluronic acid did not completely fill the microporous structure of the master mold during the casting process, and some microneedles were broken, damaged and deformed due to adhesion during demolding.

The specific embodiments described above further describe the purpose, technical solutions and beneficial effects of the present disclosure in detail. It should be understood that the above-mentioned specific embodiments are only specific embodiments of the present disclosure, and are not intended to limit the present disclosure. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present disclosure should be included within the protection scope of the present disclosure.

Claims (10)

1. a mold surface treatment method, is used for improving the demoulding effect of microneedle, is characterized in that, comprises: Cleaning the master mold with microporous structure; Use oxygen plasma to activate the cleaned master mold; A seed layer and a thin film layer are sequentially deposited on the surface of the activated master mold, wherein the thin film layer is used to reduce the free energy of the surface of the master mold. 2 . The method according to claim 1 , wherein the time range for the activation treatment is 1-10 minutes. 3 . 3 . The method according to claim 1 , wherein a Ti seed layer or a Cr seed layer is deposited on the surface of the activated master mold. 4 . 4 . The method according to claim 1 , wherein the thin film layer is an Au thin film layer, and the thickness of the Au thin film layer ranges from 5 to 200 nanometers. 5 . 5. The method according to claim 1, wherein the thickness of the seed layer is in the range of 1-20 nanometers. 6. The method according to claim 1, wherein the cleaning of the master mold with a microporous structure comprises: The master mold with the microporous structure is immersed in acetone and isopropanol solution for ultrasonic cleaning in turn; The master mold after ultrasonic cleaning was dried with nitrogen gas. 7. The method according to claim 6, wherein the time range of the ultrasonic cleaning is 5-10 minutes. 8. The method according to claim 3, wherein the thickness of the Ti seed layer or the Cr seed layer is 3-5 nanometers. 9 . The method according to claim 1 , wherein a seed layer and a thin film layer are sequentially deposited on the surface of the activated master mold by using a magnetron sputtering coating machine, an electron beam evaporation coating machine or a thermal evaporation coating machine. 10 . 10. A method for making microneedles based on the method of any one of claims 1-9, characterized in that, comprising: Cleaning the master mold with microporous structure; Use oxygen plasma to activate the cleaned master mold; A seed layer and an Au thin film layer are sequentially deposited on the surface of the activated master mold; A high-molecular polymer material is cast on the Au film layer, and after the polymer material is cured and formed, it is demolded and separated to obtain polymer microneedles.

Images