CN111331871A

CN111331871A - Mold surface treatment method and microneedle manufacturing method

Info

Publication number: CN111331871A
Application number: CN202010133816.7A
Authority: CN
Inventors: 温晓镭; 孙剑
Original assignee: University of Science and Technology of China USTC
Current assignee: University of Science and Technology of China USTC
Priority date: 2020-02-28
Filing date: 2020-02-28
Publication date: 2020-06-26

Abstract

A mold surface treatment method for improving the mold release effect of microneedles, comprising: cleaning a master mold with a micropore structure; activating the cleaned master mold by adopting oxygen plasma; and sequentially depositing a seed layer and a thin film layer on the surface of the master mold after the activation treatment, wherein the thin film layer is used for reducing the free energy of the surface of the master mold. The method can promote polymer materials to permeate and fill the microporous structure, the Au thin film layer deposited on the surface of the mold can greatly reduce the surface free energy of the mold, effectively solve the problem of adhesion of the polymer and the mold in the demolding process, improve the processing efficiency and success rate of polymer microneedles and prolong the service life of the mold. Because the Au has good biocompatibility, no toxic or harmful or dangerous chemical components are generated in the processing process, the Au is suitable for the related research of life science, and can meet the requirement of mass production. And the whole process adopts a low-temperature process, so that the heat damage to the master mold is avoided.

Description

Mold surface treatment method and microneedle manufacturing method

Technical Field

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

Background

The microneedle is a functional micro-nano structure consisting of a plurality of micron-sized needle-shaped protrusions, and is mainly used in the beauty medicine fields of skin moisturizing, transdermal drug delivery, painless immunotherapy and the like. Among them, the microneedle structure of polymer materials (such as hyaluronic acid HA, polyvinyl alcohol PVA, polylactic acid PLA, etc.) receives wide attention due to the characteristics of good biocompatibility, flexibility, high-efficiency drug loading, etc.

The method for manufacturing the polymer micro-needle structure generally needs a master mold (the material is usually polydimethylsiloxane PDMS or organic glass PMMA) as a negative mold, a plurality of micropores are processed on the master mold, then the polymer material is cast on the micropores, and after curing and forming, demolding and separation are carried out, thus obtaining the micro-needle convex structure with the shape complementary to the shape of the micropores of the negative mold.

However, under the conditions of large microneedle arrangement density, small size or large overall area, a polymer may hardly enter the interior of the micropores in the casting process, so that a microneedle protruding structure complementary to the shape of the micropores cannot be formed, or due to the large contact area between the polymer and the master mold, an adhesion phenomenon occurs during demolding, so that demolding is difficult, the microneedle structure is damaged and deformed after demolding, and the polymer remains in the micropores of the master mold. This seriously affects the processing efficiency, yield and service life of the master mold of the polymer microneedle structure.

To improve the above problems, a fluoropolymer film or a long-chain silane anti-sticking layer is coated or deposited on the surface of the mold before the polymer is cast. However, for the materials of the common master mold for microneedles such as PDMS and PMMA, the deposition efficiency and the anti-adhesion effect of the anti-adhesion layer are limited, and there are still some cases that adhesion and difficult demolding occur during demolding. In addition, the spin coating or immersion coating method involves a risk of filling fine micro-holes. The vapor deposition method is usually complicated, toxic and harmful or dangerous chemical components exist in the processing process, biocompatibility is not facilitated, special deposition equipment is needed, and the compatibility with the conventional semiconductor process is poor. Part of the vapor deposition methods require heating conditions, have potential influence on common master mold materials (such as PDMS) and may cause deformation of the microporous structure, thereby influencing the subsequent casting process. The surface treatment mode of simply depositing the fluorine-containing polymer film or the long-chain silane anti-sticking layer can not effectively promote the polymer to fill the interior of the micropores of the mould, and the cast micro-needle structure is always damaged and incomplete.

Disclosure of Invention

Technical problem to be solved

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

(II) technical scheme

According to a first aspect of embodiments of the present disclosure, there is provided a mold surface treatment method for improving a mold release effect of microneedles, including: cleaning a master mold with a micropore structure; activating the cleaned master mold by adopting oxygen plasma; and sequentially depositing a seed layer and a thin film layer on the surface of the master mold after the activation treatment, wherein the thin film layer is used for reducing the free energy of the surface of the master mold.

Alternatively, the activation treatment is performed for a time period in the range of 1 to 10 minutes.

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

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

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

Optionally, cleaning the master mold with the microporous structure includes: sequentially immersing a master mold with a microporous structure into acetone and isopropanol solution for ultrasonic cleaning; and drying the mother plate mold after ultrasonic cleaning by adopting nitrogen.

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

Optionally, the Ti seed layer or the Cr seed layer has a thickness of 3-5 nanometers.

Optionally, a seed layer and a 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.

According to a second aspect of the embodiments of the present disclosure, there is provided a microneedle manufacturing method, comprising: cleaning a master mold with a micropore structure; activating the cleaned master mold by adopting oxygen plasma; sequentially depositing a seed layer and an Au thin film layer on the surface of the master mould after the activation treatment; and casting a high-molecular polymer material on the Au thin film layer, and demolding and separating after the polymer material is solidified and molded to obtain the polymer microneedle.

(III) advantageous effects

The present disclosure provides a mold surface treatment method and a microneedle manufacturing method, which have the following beneficial effects:

1. the method carries out oxygen plasma activation treatment on the surface of the master mold, can promote polymer materials to permeate and fill the microporous structure, can greatly reduce the free energy of the surface of the mold by depositing Au on the surface of the mold, effectively solves the problem of adhesion of the polymer and the mold in the demolding process, improves the processing efficiency and success rate of polymer microneedles, and prolongs the service life of the mold.

2. Because the biocompatibility of Au is good, no toxic or harmful or dangerous chemical components are generated in the processing process, and the Au is suitable for the related research of life science.

3. The method is simple to operate, can be realized by using conventional semiconductor processing equipment, has good compatibility with a semiconductor processing process chain, and can meet the requirement of mass production. The whole process adopts a low-temperature process, so that the heat damage to the master mold can be avoided.

Drawings

For a more complete understanding of the present disclosure and the advantages thereof, reference is now made to the following descriptions 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 with the description serve to explain the principles of the disclosure. Wherein:

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

fig. 2 schematically illustrates a flow chart of a method of fabricating a polymer microneedle, according to an exemplary embodiment of the present disclosure;

fig. 3 shows a microscopic structure diagram of a hyaluronic acid microneedle array obtained after casting hyaluronic acid, curing, molding and demolding after treating the surface of a PDMS master mold according to a mold surface treatment method of an exemplary embodiment of the present disclosure;

FIG. 4 shows a structural microstructure diagram of hyaluronic acid obtained by directly casting hyaluronic acid without surface treatment of a master mold, curing, molding and demolding;

fig. 5 shows a microstructure diagram of a hyaluronic acid microneedle array obtained after casting hyaluronic acid, curing, molding and demolding after treating the surface of a PDMS master mold by using a conventional method (vapor deposition of a long-chain silane anti-sticking layer).

Detailed Description

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

The embodiment of the disclosure provides a method for processing the surface of a mold, which comprises the step of cleaning a master mold with a micropore structure. And activating the cleaned master mould by adopting oxygen plasma. And sequentially depositing a seed layer and a film on the surface of the master mould after the activation treatment. The method can improve the demolding effect of the polymer microneedle.

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

S101, cleaning the master mold with the micropore structure.

In a feasible manner of this embodiment, the master mold with the microporous structure may be sequentially immersed in acetone and isopropanol solution for ultrasonic cleaning, where the ultrasonic cleaning time is in a range of 5-10 minutes, for example, the ultrasonic cleaning time may be 5 minutes, and the disclosure is not limited thereto. The master mold may be, for example, a PDMS template.

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

And S102, activating the cleaned master mold by adopting oxygen plasma.

In a feasible manner of this embodiment, the cleaned master mold may be placed in an apparatus capable of generating oxygen plasma, and the oxygen plasma is used to perform an activation process, so as to promote the polymer material to penetrate into and fill the microporous structure of the master mold. The time range of the activation treatment is 1 to 10 minutes, for example, the activation treatment can be carried out for 5 minutes, and the disclosure is not limited.

In a feasible manner of this embodiment, the apparatus capable of generating oxygen plasma includes, but is not limited to, an apparatus with an oxygen plasma bombardment function, such as a reactive ion etcher RIE, an inductively coupled plasma etcher ICP, a plasma photoresist remover, and the like. Preferably, a reactive ion etcher is used, and the activation treatment time is 5 minutes.

S103, a seed layer and a thin film layer are sequentially deposited on the surface of the master mold after the activation treatment, wherein the thin film layer is used for reducing the free energy of the surface of the master mold.

In a feasible manner of this embodiment, the master mold after the activation process is placed in a vacuum deposition apparatus, and a seed layer and a thin film layer are sequentially deposited to reduce the free energy of 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 preferably has a thickness of 3-5 nm, but the disclosure is not limited thereto. The thin film layer may be an Au thin film layer, for example, having a thickness of 5-200 nm, with a preferred thickness range of 10-20 nm.

In one possible embodiment, the vacuum coating apparatus includes, but is not limited to, a magnetron sputtering coater, an electron beam evaporation coater, a thermal evaporation coater, and the like, and preferably, a magnetron sputtering coater is used.

Based on the processing method of the mold surface, the embodiment of the disclosure also provides a manufacturing method of the polymer microneedle. Fig. 2 schematically illustrates a flow chart of a method of fabricating a polymer microneedle, according to an exemplary embodiment of the present disclosure. As shown in fig. 2, the method may include operations S201 to S204, for example.

S201, cleaning the master mould with the micropore structure.

And S202, activating the cleaned master mold by adopting oxygen plasma.

S203, a seed layer and a film layer are sequentially deposited on the surface of the master mould after the activation treatment.

And S204, casting a high-molecular polymer material on the Au thin film layer, and demolding and separating after the polymer material is solidified and molded to obtain the polymer microneedle.

In a feasible manner of this embodiment, the polymer material may be, for example, hyaluronic acid, and the hyaluronic acid is transferred to a ventilation drying environment after being vacuumized for 1 hour, and then is separated from the mold after the hyaluronic acid is cured and molded, so as to obtain the hyaluronic acid microneedle array structure.

For details, please refer to the above embodiment of the mold surface treatment method, which is not described herein again.

In the method, oxygen plasma activation treatment is performed on the surface of the master mold to promote the polymer material to penetrate and fill the microporous structure. Au deposited on the surface of the die can greatly reduce the surface free energy of the die, and the problem of adhesion between a polymer and the die in the demolding process is effectively solved. And because the biocompatibility of Au is good, no toxic or harmful or dangerous chemical component is generated in the processing process, and the Au-Au. The surface treatment mode uses conventional semiconductor processing equipment, is suitable for mass production, adopts a low-temperature process, and does not cause heat damage to the master mold.

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

Fig. 3 shows a microstructure diagram of a hyaluronic acid microneedle array obtained after casting hyaluronic acid, curing, molding and demolding after treating the surface of a PDMS master mold according to a mold surface treatment method in an exemplary embodiment of the present disclosure. Fig. 3 shows that the microneedles are intact in morphology and complete in array, indicating that hyaluronic acid completely fills the master mold microporous structure during casting and that no adhesion problems occur during demolding.

Fig. 4 shows a structural microstructure of hyaluronic acid obtained by directly casting hyaluronic acid without surface treatment of a master mold, curing, molding and demolding. Fig. 4 shows that the desired microneedle shape was not formed, and only a portion of the microneedle base remained, indicating that the hyaluronic acid did not completely penetrate and fill the interior of the master mold pore structure during casting.

Fig. 5 shows a microstructure diagram of a hyaluronic acid microneedle array obtained after casting hyaluronic acid, curing, molding and demolding after treating the surface of a PDMS master mold by using a conventional method (vapor deposition of a long-chain silane anti-sticking layer). Fig. 5 shows that the microneedle array is incomplete and has more defects, which indicates that hyaluronic acid does not completely fill the microporous structure of the master mold during casting, and that some microneedles are broken, damaged and deformed due to adhesion during demolding.

The above-mentioned embodiments are intended to illustrate the objects, aspects and advantages of the present disclosure in further detail, and it should be understood that the above-mentioned embodiments are only illustrative of the present disclosure and are not intended to limit the present disclosure, and any modifications, equivalents, improvements and the like made within the spirit and principle of the present disclosure should be included in the scope of the present disclosure.

Claims

1. A mold surface treatment method for improving the mold release effect of microneedles, comprising:

cleaning a master mold with a micropore structure;

activating the cleaned master mold by adopting oxygen plasma;

and sequentially depositing a seed layer and a thin film layer on the surface of the master mold after the activation treatment, wherein the thin film layer is used for reducing the free energy of the surface of the master mold.

2. The method according to claim 1, wherein the activation treatment is performed for a time ranging from 1 to 10 minutes.

3. The method of claim 1, wherein a Ti seed layer or a Cr seed layer is deposited on the master mold surface after the activation process.

4. The method of claim 1, wherein the thin film layer is an Au thin film layer having a thickness in a range of 5-200 nm.

5. The method of claim 1, wherein the seed layer has a thickness in the range of 1-20 nm.

6. The method of claim 1, wherein the cleaning the master mold with the micro-porous structure comprises:

sequentially immersing the master mold with the microporous structure into acetone and isopropanol solution for ultrasonic cleaning;

and drying the mother plate mold after ultrasonic cleaning by adopting nitrogen.

7. The method of claim 6, wherein the time of the ultrasonic cleaning is in the range of 5-10 minutes.

8. The method of claim 3, wherein the Ti or Cr seed layer has a thickness of 3-5 nanometers.

9. The method of claim 1, wherein the seed layer and the thin film layer are sequentially deposited on the surface of the master mold after the activation process by a magnetron sputtering coater, an electron beam evaporation coater, or a thermal evaporation coater.

10. A method of microneedle fabrication based on the method of any one of claims 1 to 9, comprising:

cleaning a master mold with a micropore structure;

activating the cleaned master mold by adopting oxygen plasma;

sequentially depositing a seed layer and an Au thin film layer on the surface of the master mould after the activation treatment;

and casting a high-molecular polymer material on the Au thin film layer, and demolding and separating after the polymer material is solidified and molded to obtain the polymer microneedle.