阅读说明：本技术 微结构快速成型和脱模的系统及方法 (System and method for rapid forming and demoulding of microstructure ) 是由 潘书婷 游卫龙 郭太松 于 2021-02-25 设计创作，主要内容包括：本发明涉及微结构制造技术领域,尤其涉及微结构快速成型和脱模的系统及方法,所述微结构快速成型和脱模的系统包括微结构主模具和引流座,所述微结构主模具上表面设有微结构阵列,所述引流座底部开设有引流通道,所述微结构主模具表面的微结构阵列穿过引流通道与引流座固定连接,以使所述引流通道与所述微结构主模具封闭形成成型腔体；所述成型腔体外设有第一真空吸盘；所述引流座外壁设有外部激励器。本发明在微结构成型及脱模过程中引入可控的机械结构分离法、真空吸附方法或外加激励方法,促进微结构快速成型和脱模,增强了微结构制作工艺的自动化、成型结构的均一性和良率。(The invention relates to the technical field of microstructure manufacturing, in particular to a system and a method for quickly forming and demoulding a microstructure, wherein the system for quickly forming and demoulding the microstructure comprises a main microstructure mould and a drainage seat, a microstructure array is arranged on the upper surface of the main microstructure mould, a drainage channel is arranged at the bottom of the drainage seat, and the microstructure array on the surface of the main microstructure mould penetrates through the drainage channel to be fixedly connected with the drainage seat, so that the drainage channel and the main microstructure mould are closed to form a forming cavity; a first vacuum chuck is arranged outside the forming cavity; and an external exciter is arranged on the outer wall of the drainage seat. The invention introduces a controllable mechanical structure separation method, a vacuum adsorption method or an external excitation method in the micro-structure forming and demoulding process, promotes the micro-structure to be rapidly formed and demoulded, and enhances the automation of the micro-structure manufacturing process, the uniformity of the formed structure and the yield.)

1. The system for quickly forming and demolding the microstructure is characterized by comprising a microstructure main mold and a drainage seat, wherein a microstructure array is arranged on the upper surface of the microstructure main mold, a drainage channel is formed in the bottom of the drainage seat, and the microstructure array on the surface of the microstructure main mold penetrates through the drainage channel to be fixedly connected with the drainage seat, so that the drainage channel and the microstructure main mold are sealed to form a forming cavity; a first vacuum chuck is arranged outside the forming cavity; and an external exciter is arranged on the outer wall of the drainage seat.

2. The system of claim 1, wherein the external actuator is an ultrasonic generator or an electric controller.

3. The system of claim 1, wherein the microstructured master mold is provided with a heater at a bottom thereof.

4. The system of claim 1, wherein the microstructured master mold bottom is provided with a second vacuum chuck.

5. The system of claim 1, wherein the micro-structured array is comprised of a plurality of micro-needles or micro-porous bodies having a diameter of less than 100 μm at their apex and a height/depth of less than 1000 μm; the depth-to-width ratio of the micro-needle or the micro-pore body is 1 (1-5).

6. The system of claim 1, wherein the drainage seat is a split removable structure.

7. The system of claim 6, wherein the drainage seat comprises a bottom plate and a side plate, the side plate being threadably connected to the bottom plate.

8. The system of claim 1, wherein the drainage seat comprises a bottom plate and side plates, and the side plates, the bottom plate and the microstructure main mold form a forming cavity in a wedge-shaped structure.

9. A method for rapid prototyping and demolding of microstructures using the system of any of claims 1-8, comprising the steps of:

(1) injecting a liquid material to be molded into the molding cavity, utilizing a first vacuum chuck to extract vacuum, opening an external exciter to promote the liquid material to be molded to be rapidly injected into the molding cavity, standing and molding to obtain a microstructure;

(2) and adsorbing the microstructure by using a first vacuum chuck, opening an external exciter, and enabling the formed microstructure and the microstructure main die to move relatively to finish demoulding to obtain the microstructure product.

10. The method according to claim 9, wherein in the step (1), the material to be molded is selected from one or more of polymer, hyaluronic acid and protein molecule solution;

the external exciter is an ultrasonic generator, the power of the ultrasonic generator is 1-2000W, the frequency is 10 KHz-100 MHz, and the time of ultrasonic action is 5 s-1 h;

in the step (2), the diameter of the most pointed part of the microstructure product is less than 100 μm, and the height/depth is less than 1000 μm; the depth-to-width ratio of the microstructure product is 1 (1-5).

Technical Field

The invention relates to the technical field of microstructure manufacturing, in particular to a system and a method for quickly forming and demoulding a microstructure.

Background

The micro-needle is a novel drug delivery system, promotes the permeation of drugs or biological molecules into the skin by forming micro/nano-level channels on the surface of the skin, and has great research and application potential in the fields of medicine, beauty and medicine. The microneedle based on polymer or protein molecules can strongly promote the market application of the microneedle due to the good biocompatibility and the characteristic of easy degradation.

The polymer or protein molecule micro-needle, such as PDMS micro-needle or PDMS micro-needle negative template, silk fibroin micro-needle, etc., has the characteristics of high depth-to-width ratio, fine structure, low mechanical strength, and often has the problems of slow forming process, micro-structure breakage even micro-needle breakage during mold turning or demolding, etc.

Currently, manual demolding is often used in laboratories to demold polymeric or protein microneedle/microneedle negative templates, and is assisted by chemical or physical methods. Chemical methods, such as coating the microneedle mold surface with a hydrophobic material (e.g., teflon) or silanizing the mold, can increase the hydrophobicity of the microneedle mold surface and facilitate the demolding process, and the mold release agent can also assist the demolding process. Physical methods, such as freeze-drying treatment of hydrogel microneedles, shrink the microneedle structure and facilitate separation of the microneedles from the mold.

However, the above method has the following problems: the chemical method related to the coating of the hydrophobic material or the silanization modification needs to introduce an additional chemical modification process, the operation is complex, the problems of residual surface chemical materials or residual process products of the formed microneedle are not clear, and the release agent has no obvious effect on the microneedle device with high aspect ratio. Physical methods, the protocols that produce structural shrinkage, are limited for microneedle materials and are also not applicable for high density microneedle structures.

Disclosure of Invention

In order to overcome the problems in the prior art, the invention provides a system for rapidly forming and demolding a microstructure, which can enhance the automation of microstructure manufacturing, the uniformity of a formed structure and the yield.

The invention also provides a method for rapidly forming and demolding the microstructure by using the system.

In order to achieve the purpose, the invention adopts the following technical scheme:

the system for quickly forming and demolding the microstructure comprises a microstructure main mold and a drainage seat, wherein a microstructure array is arranged on the upper surface of the microstructure main mold, a drainage channel is formed in the bottom of the drainage seat, and the microstructure array on the surface of the microstructure main mold penetrates through the drainage channel to be fixedly connected with the drainage seat, so that the drainage channel and the microstructure main mold are closed to form a forming cavity; a first vacuum chuck is arranged outside the forming cavity; and an external exciter is arranged on the outer wall of the drainage seat.

According to the system, the method that the first vacuum chuck vacuumizes or applies external excitation to the liquid material to be molded in the molding cavity can promote air bubbles between the microstructure main mold and the drainage seat solid and the high-viscosity liquid (the liquid material to be molded) to be discharged, so that the liquid material to be molded is promoted to be rapidly and fully filled into the microstructure of the mold. The external exciter can generate slight vibration on the drainage seat, so that the filling rate of the liquid material to be molded can be increased in the molding stage, the molding rate can be increased, and the demolding efficiency can be increased in the demolding stage. In addition, a mechanical separation method can be directly adopted to promote demoulding in the demoulding process. For example, a threaded connection method is adopted, so that relative displacement is generated between the side plate and the floor, and the micro-structure formed in the side plate and the side plate are driven to synchronously move, and the separation of the forming structure and the main template is further realized; the first vacuum chuck is adopted to act on the surface of the formed microstructure to generate uniform adsorption force on the surface of the formed microstructure, so that the formed microstructure can be conveniently stripped from the surface of the microstructure main die, and the damage or fracture of the microstructure is avoided.

Preferably, the external actuator is an ultrasonic generator or an electric controller.

For some special protein molecules, such as silk fibroin molecules, during the molding process, ultrasonic excitation is applied, and the gel state transition of the protein solution can be promoted, so that the silk fibroin gel microneedle is formed. In the demolding process, the drainage seat is slightly vibrated by adopting ultrasonic excitation, so that slight relative motion is generated between the solid-state microstructure in the molding cavity and the microstructure main mold, the separation of the solid-state microstructure and the microstructure main mold is finally promoted, and the damage or the fracture of the microstructure is avoided. The electric controller electrically controls the motion of the side plate of the drainage seat to control the motion, and the motion speed is 10-500 μm/min.

Preferably, a heater is arranged at the bottom of the microstructure main mold. The temperature controllability can be realized by applying the heater, and the molding efficiency can be accelerated by increasing the temperature; furthermore, different temperature parameters can change the mechanical strength of the microstructure.

Preferably, the bottom of the microstructure main die is provided with a second vacuum chuck. The second vacuum chuck can fix the microstructure main die by utilizing uniform adsorption force before molding, so that the stability is improved; after the microstructure is formed, the formed microstructure needs to be separated from the microstructure main mold, i.e. a demolding process is performed. In the process, the second vacuum chuck is adopted to act on the surface of the microstructure main die to generate uniform adsorption force, and under the combined action of other external excitation or mechanical separation methods, the formed microstructure is promoted to be stripped from the surface of the microstructure main die, so that the microstructure is prevented from being damaged or broken.

Preferably, the microstructure array is composed of a plurality of microstructure bodies, the microstructure array is composed of a plurality of micro-needles or micro-pore bodies, the diameter of the most pointed part of each micro-needle or micro-pore body is less than 100 μm, and the height/depth is less than 1000 μm; the depth-to-width ratio of the micro-needle or the micro-pore body is 1 (1-5). The microstructure body is a solid microstructure made of metal, silicon, glass, polymer, protein or other materials.

The system of the present invention can be applied, but not limited to, in the preparation of polymer or protein molecular microstructures, such as PDMS microneedle or PDMS microneedle negative template, hyaluronic acid microneedle/microneedle negative template, silk fibroin microneedle/microneedle negative template, etc. PDMS is polydimethylsiloxane, a polymer material, and is commonly used for the preparation of microfluidic chips. The silk fibroin is natural polymer fibrin extracted from silk. Hyaluronic acid, also known as hyaluronic acid, is a natural biomolecule present in skin and other tissues, and can also be obtained synthetically. The microstructure prepared from the material has the characteristics of high depth-to-width ratio, fine structure and low mechanical strength, and often has the problems of slow forming process, microstructure damage, microneedle fracture and the like during mould turning or demoulding. Due to the high aspect ratio structure of the main mold, the time for completely filling the microstructure main mold with the solution to be formed is long, and the problems of residual bubbles, insufficient pouring and the like are easily caused, so that the problems of low yield of the formed microstructure, low mechanical strength and the like are finally caused. The system of the invention can effectively solve the problems.

When the micro-structure main die is in a needle-shaped structure (microneedle array), the micro-structure main die can be used for manufacturing a microporous structure made of polymer/protein materials, and the structure can be used as a microneedle negative template; when the micro-structure main mold is a micropore/groove-shaped structure (micropore array), the micro-structure main mold can be used for manufacturing a needle structure made of polymer/protein materials, and can be directly used as a microneedle or used as a secondary microneedle main mold in a microneedle template copying process.

Preferably, the drainage seat is of a split detachable structure.

Preferably, the drainage seat comprises a bottom plate and a side plate, and the side plate is in threaded connection with the bottom plate. By adjusting the threaded connection or other detachable mechanical mechanisms and the method for electrically controlling the relative movement, the separation of the solid structure in the forming cavity and the microneedle main mold is promoted, and the damage to the microneedle main mold and the formed microstructure is reduced.

Preferably, the drainage seat comprises a bottom plate and a side plate, a forming cavity formed by the side plate, the bottom plate and the microstructure main die is of a wedge-shaped structure, and the wedge-shaped structure can reduce resistance between a formed microstructure and the microstructure main die and is convenient for demoulding.

A method for rapid prototyping and demolding of a microstructure using any of the above systems, comprising the steps of:

(1) injecting a liquid material to be molded into the molding cavity, utilizing a first vacuum chuck to extract vacuum, opening an external exciter to promote the liquid material to be molded to be rapidly injected into the molding cavity, standing and molding to obtain a microstructure structure;

(2) and adsorbing the microstructure by using a first vacuum chuck, opening an external exciter, and enabling the formed microstructure structure and the microstructure main die to move relatively to finish demoulding to obtain the microstructure product.

The invention introduces a controllable mechanical structure separation method, a vacuum adsorption method or an external excitation method in the micro-structure forming and demoulding process, promotes the micro-structure to be rapidly formed and demoulded, and enhances the automation of the micro-structure manufacturing process, the uniformity of the formed structure and the yield.

Preferably, in the step (1), the material to be molded is selected from one or more of polymer, hyaluronic acid and protein molecule solution.

Preferably, the external exciter is an ultrasonic generator, the power of the ultrasonic generator is 1-2000W, the frequency is 10 KHz-100 MHz, the time of ultrasonic action is 5 s-1 h, and the time interval of action is 1 second-30 minutes.

The action strength is too low due to too low power of the ultrasonic wave, so that the solution cannot be promoted to enter the cavity or the uniform liquefaction treatment effect cannot be realized; too high a temperature may cause increased solution temperature or damage to the ultrasonic transducer; the change of the frequency of the ultrasonic wave can correspondingly change the working mode and effect of the liquefaction action; the ultrasound wave action interval time refers to the time period during which no ultrasound action is present when a pulsed ultrasound signal is applied. The ultrasonic signal of pulse excitation is applied to reduce the temperature of the solution, improve the working efficiency and change the effect of the ultrasonic on the liquid finely.

Preferably, the diameter of the most pointed part of the microstructure product is less than 100 μm, and the height/depth is less than 1000 μm; the depth-to-width ratio of the microstructure product is 1 (1-5).

Therefore, the invention has the following beneficial effects:

(1) according to the system, the evacuation and/or external excitation are adopted to promote the discharge of bubbles between the microstructure main die and the drainage seat solid and the high-viscosity liquid, so that the liquid material to be molded is promoted to be rapidly and fully filled into the microstructure of the die, and the molding efficiency is accelerated; one or more of vacuum suction, mechanical structure separation and external excitation is/are combined to promote relative motion between the forming microstructure and the microstructure main die to promote smooth demolding of the forming microstructure, so that damage or fracture of the microstructure is avoided;

(2) the invention introduces a controllable mechanical structure separation method, a vacuum adsorption method or an external excitation method in the micro-structure forming and demoulding process, promotes the micro-structure to be rapidly formed and demoulded, and enhances the automation of the micro-structure manufacturing process, the uniformity of the formed structure and the yield.

Drawings

Fig. 1 is a schematic structural view of a system for rapid molding and demolding of a female microneedle mold plate according to example 1.

Fig. 2 is a schematic view of the internal structure of fig. 1.

Fig. 3 is a schematic structural view of a microneedle master template.

Fig. 4 is a schematic view of an assembly structure of the microneedle master template and the drainage base in example 1.

FIG. 5 is a schematic view of the assembly structure of the microporous master template and the drainage seat in example 2.

Fig. 6 is a schematic view of an assembly structure of the microneedle master template and the drainage base in example 3.

Fig. 7 is a schematic structural view of the microneedle master template and the molded microneedle negative template in example 1.

Fig. 8 is a schematic structural view of the microporous master template and the molded microneedles in example 2.

In the figure, an upper box body 1, a lower box body 2, a feeding bin door 3, a micro-needle main die 4, a drainage seat 5, a micro-needle array 6, a micro-needle body 7, a bottom plate 8, a side plate 9, a screw 10, a drainage channel 11, a forming cavity 12, a first vacuum chuck 13, a circuit 14, a heater 15, a forming micro-needle female die plate 16, a micro-hole main die 17, a forming micro-needle 18 and a micro-hole array 19.

Detailed Description

The technical solution of the present invention is further specifically described below by using specific embodiments and with reference to the accompanying drawings.

In the present invention, all the equipment and materials are commercially available or commonly used in the art, and the methods in the following examples are conventional in the art unless otherwise specified.

Example 1

As shown in fig. 1, a system for rapid forming and demolding of a microneedle negative template comprises an upper box body 1, a lower box body 2, a microneedle main mold 4 and a drainage seat 5 (fig. 2) which are arranged in the upper box body and the lower box body, wherein the upper end of the upper box body is provided with a feeding bin gate 3, the upper surface of the microneedle main mold is provided with a microneedle array 6 (fig. 3), the microneedle array is composed of a plurality of microneedle bodies 7, the diameter of the bottom of each microneedle body is 200 μm, the diameter of the tip is 10 μm, and the height of each microneedle is 600 μm; the aspect ratio is 1: 3; the schematic view of the assembly structure of the microneedle master template and the drainage seat is shown in fig. 4, the drainage seat comprises a bottom plate 8 and a side plate 9, and the side plate is in threaded connection with the bottom plate through a screw 10. A drainage channel 11 is formed at the bottom of the drainage seat, and a microneedle array on the surface of the microneedle main die penetrates through the drainage channel to be fixedly connected with the drainage seat, so that the drainage channel and the microneedle main die are closed to form a forming cavity 12; a first vacuum chuck 13 is arranged outside the molding cavity; the outer wall of the drainage seat is connected with an ultrasonic generator (not shown in the figure) through a line 14, and the bottom of the microneedle main mould is provided with a heater 15.

The method for rapidly forming and demolding the microneedle negative template by adopting the system of the embodiment comprises the following steps of:

(1) opening a feeding bin gate 3 to inject liquid Polydimethylsiloxane (PDMS) into the molding cavity, utilizing a first vacuum sucker 13 to extract vacuum, opening an ultrasonic generator, adjusting the power of the ultrasonic generator to be 60W, the frequency to be 20KHz, the ultrasonic action time to be 30s, promoting the liquid material to be molded to be rapidly injected into the molding cavity, opening a heater 15, adjusting the temperature to be 80 ℃, standing for 2 hours, and obtaining a PDMS micro-needle negative template;

(2) removing the screw 10, adsorbing the PDMS microneedle negative template by using a first vacuum chuck 13, turning on an ultrasonic generator, adjusting the power of the ultrasonic generator to 3W, the frequency to 20KHz, the time of ultrasonic action to 1s, the interval to 1s, the relative motion between the molded PDMS microneedle negative template and the microneedle main mold, and completing demolding, wherein the total time of ultrasonic action (demolding time) is 1 minute, so as to obtain a PDMS microneedle negative template product (fig. 7, molded microneedle negative template 16).

Example 2

The utility model provides a system of micropin rapid prototyping and drawing of patterns, includes last box, lower box, and locate box and the internal micropore master mould and the drainage seat of lower box, goes up the box upper end and has seted up the feed bin door, and the assembly structure sketch map of micropore master template and drainage seat is as shown in figure 5, and the drainage seat includes bottom plate 8 and curb plate 9, and the curb plate passes through screw 10 and bottom plate threaded connection. The bottom of the drainage seat is provided with a drainage channel 11, the upper surface of the micropore main die 17 is provided with a micropore array 19, the micropore array is composed of a plurality of micropore bodies, the diameter of the bottom of each micropore body is 10 micrometers, the diameter of the top of each micropore body is 150 micrometers, and the depth of each micropore body is 450 micrometers; the aspect ratio is 1: 3; the micropore main die compresses the drainage channel and is fixedly connected with the drainage seat, so that the drainage channel and the microneedle main die are closed to form a forming cavity; a first vacuum chuck is arranged outside the molding cavity; the outer wall of the drainage seat is provided with an ultrasonic generator, and the bottom of the micropore main die is provided with a second vacuum sucker.

The method for rapidly forming and demolding the microneedle by using the system of the embodiment comprises the following steps:

(1) injecting silk fibroin molecular solution into the molding cavity, utilizing a first vacuum sucker to extract vacuum, utilizing a second vacuum sucker to extract vacuum to adsorb and fix the micropore main mold, opening an ultrasonic generator, adjusting the power of the ultrasonic generator to be 50W, adjusting the frequency to be 20KHz, adjusting the ultrasonic action time to be 5s, adjusting the action time interval to be 3s and the action frequency to be 10 times, promoting the liquid material to be molded to be rapidly injected into the molding cavity, and simultaneously promoting the silk fibroin solution to be converted to a gel state. Turning on a heater, adjusting the temperature to be 30 ℃, standing, and forming for 24 hours to obtain the silk fibroin gel microneedle 18;

(2) removing the screw 10, adsorbing the microstructure by using a first vacuum chuck, turning on an ultrasonic generator, adjusting the power of the ultrasonic generator to 5W, the frequency to 33KHz, the ultrasonic action time to 1s, the action time interval to 1s, allowing the molded silk fibroin gel microneedle to move relative to the micropore main mold 17, completing demolding, and allowing the total ultrasonic action time (demolding time) to be 1 min to obtain a silk fibroin gel microneedle product (fig. 8, molded microneedle 18).

Example 3

A system for quickly forming and demoulding a microneedle negative template comprises an upper box body, a lower box body, a microneedle main mould and a drainage seat, wherein the microneedle main mould and the drainage seat are arranged in the upper box body and the lower box body, the upper end of the upper box body is provided with a feeding bin gate, the upper surface of the microneedle main mould is provided with a microneedle array, the microneedle array consists of a plurality of microneedle bodies, the diameter of the bottom of each microneedle body is 100 micrometers, the diameter of the tip is 10 micrometers, and the height of each microneedle body is 500 micrometers; the aspect ratio is 1: 5; the schematic view of the assembly structure of the microneedle main mold and the drainage seat is shown in fig. 6, the drainage seat is composed of annular side plates 9, a drainage channel is formed by a cavity surrounded by the annular side plates, and a microneedle array on the surface of the microneedle main mold penetrates through the drainage channel to be fixedly connected with the drainage seat, so that the drainage channel and the side plates of the microneedle main mold are closed to form a forming cavity 12 with a wedge-shaped structure; a first vacuum chuck is arranged outside the molding cavity; the outer wall of the drainage seat is provided with an electric controller to electrically control the movement of the wedge-shaped structure, and the bottom of the microneedle main die is provided with a second vacuum chuck.

The method for rapidly forming and demolding the microneedle negative template by adopting the system of the embodiment comprises the following steps of:

(1) injecting liquid hyaluronic acid into the molding cavity, extracting vacuum by using a first vacuum chuck, extracting vacuum by using a second vacuum chuck to fix the microneedle main mold, standing at normal temperature by using an electric controller, and molding for 24 hours to obtain a hyaluronic acid microneedle negative template;

(2) and adsorbing the hyaluronic acid micro-needle by using a first vacuum chuck, opening an electric controller, adjusting the action strength of the electric controller to enable the movement speed of the wedge-shaped structure to be 200 mu m/min, enabling the formed hyaluronic acid micro-needle negative template and the micro-needle main mold to move relatively, finishing demolding, and enabling the total demolding time to be 3 minutes to obtain the hyaluronic acid micro-product negative template.

The above description is only a preferred embodiment of the present invention, and is not intended to limit the present invention in any way, and other variations and modifications may be made without departing from the spirit of the invention as set forth in the claims.