KR101025904B1 - Fabrication Apparatus of Polymeric Microbeads Comprising Microfluidic Chip Increasing UV Irradiation Time and Fabrication Method of Polymeric Microbeads Using the Same - Google Patents

Abstract

The present invention relates to a microbead manufacturing apparatus including a microfluidic chip with increased ultraviolet irradiation time and a method for producing polymer microbeads using the same, more specifically, a monomer injection port (1b), a continuous phase injection port (1a), a continuous phase And a microfluidic chip including a junction point (2a) of the monomer and a microchannel (2) and an outlet (2b), and a water tank (5), wherein the monomer injected into the monomer inlet (1b) includes the continuous phase and the monomer. The monomer droplet formed passing through the junction point (2a) of the micro-channel, characterized in that the micro-channel (2) is discharged through the outlet (2b) is completely cured in real time by the ultraviolet irradiation means 6 to produce a polymer microbead The present invention relates to a bead manufacturing apparatus and a polymer microbead manufacturing method using the microbead manufacturing apparatus. Microbead manufacturing apparatus of the present invention is a device that can increase the UV irradiation time for the monomer droplets formed in the microfluidic chip can be used to prepare a fully cured polymer beads in real time.

Microfluidic Chips, Photopolymerization, Monodispersion, Polyurethanes, Micro Beads

Description

Fabrication Apparatus of Polymeric Microbeads Comprising Microfluidic Chip Increasing UV Irradiation Time and Fabrication Method of Polymeric Microbeads Using the Same}

The present invention relates to a microbead manufacturing apparatus including a microfluidic chip with increased ultraviolet irradiation time and a method for producing polymer microbeads using the same, and more particularly, to increase ultraviolet irradiation time for monomer droplets formed in the microfluidic chip. A method of making a microbead manufacturing apparatus which can be used and producing a fully cured polymer beads using the apparatus.

Generally, in order to obtain micro-sized polymer beads, emulsion polymerization is performed in which a liquid droplet, which is not mixed with a monomer to be polymerized, is continuously used to form monomer droplets through stirring, and then cured beads are obtained by UV irradiation or heating. Used. This method, however, made it difficult to obtain monodisperse beads of uniform particle size.

Recently, microfluidic chips have been used to obtain monodisperse polymer beads of uniform size. Spherical monomer droplets are formed by injecting together a monomer to be reacted with a monomer that is not mixed with the monomer through a flow path formed in the microfluidic chip, and a method of obtaining polymer beads solidified by irradiation with ultraviolet rays is mainly used. .

However, due to the characteristics of the microfluidic chip, the irradiation time of ultraviolet rays is relatively shorter than that of conventional emulsion polymerization, so that curing is completely performed when using a monomer requiring a long ultraviolet irradiation time or increasing the flow rate of the fluid to increase the production speed. Beads could not be obtained in real time. Even if the cured beads were obtained to some extent, the irradiation process was required after collecting the beads obtained first and irradiating them again with UV. In addition, since ultraviolet irradiation is performed in the microchannel of the microfluidic chip, it is impossible to obtain polymer microbeads having a diameter larger than the height or width of the microchannel.

Accordingly, the inventors of the present invention devised a method of continuously manufacturing the polymer microbeads, by applying a fluid outlet directed vertically downward to the microfluidic chip breakthrough UV irradiation time for the photocurable polymer droplets exiting through the outlet The present invention was completed by confirming that the polymer beads could be expanded to obtain fully cured polymer beads.

The present invention has been made to solve the problems of the prior art as described above in the manufacturing process of polymer microbeads using the conventional microfluidic chip. After all, it is an object of the present invention to provide a microbead manufacturing apparatus and a manufacturing method using the same that can be produced in real time a fully cured polymer microbeads without restriction on the flow rate of the fluid inside the microfluidic chip.

In order to achieve the above object, the present invention is a microfluidic chip including a monomer inlet (1b), a continuous phase inlet (1a), a junction point (2a) of the continuous phase and the monomer, a micro-channel (2) and outlet (2b), And a water tank (5), wherein monomer droplets formed while the monomer injected into the monomer injection port (1b) pass through the junction point (2a) of the continuous phase and the monomer are discharged through the discharge port (2b) through the micro-channel (2) While being completely cured in real time by the ultraviolet irradiation means 6 provides a microbead manufacturing apparatus characterized in that the polymer microbeads are manufactured.

The present invention also provides a polymer microbead manufacturing method using the microbead production apparatus.

Hereinafter, the present invention will be described in detail.

The present invention is to put the microfluidic chip in the tank containing the continuous phase to make the outlet of the fluid to the bottom of the microfluidic chip, the monomer droplets generated in the microfluidic chip is discharged downward through the outlet, the monomer droplet is a continuous phase It is characterized by the production of fully cured polymer microbeads in real time by irradiating ultraviolet rays while moving downwards by gravity in the contained bath.

The present invention includes a monomer inlet 1b, a continuous phase inlet 1a, a junction point 2a of a continuous phase and a monomer, a microfluidic chip including a microchannel 2 and an outlet 2b, and a water tank 5. The monomer injected into the monomer inlet 1b passes through the junction 2a of the continuous phase and the monomer, and the monomer droplets are discharged through the outlet 2b through the micro-channel 2 and the ultraviolet irradiation means 6. It provides a micro-bead manufacturing apparatus characterized in that the polymer microbeads are prepared by completely curing in real time by the.

In the microbead manufacturing apparatus of the present invention, the outlet 2b is preferably directed vertically downward to increase ultraviolet irradiation time, and the water tank 5 is disposed inside the microfluidic chip at the boundary of the outlet 2b. It is preferable that the continuous phase 4 is contained in order to make external conditions the same.

In addition, in the microbead production apparatus of the present invention, in order to increase the time until the monomer droplets discharged through the outlet (2b) to the bottom of the water tank (5), it is directed vertically downward to the bottom of the microfluidic chip It is preferable that the microbead manufacturing apparatus base 3 is provided, and the monomer inlet 1b and the continuous phase inlet 1a are each composed of two.

The present invention also provides a polymer microbead manufacturing method using the microbead production apparatus.

In the polymer microbead production method of the present invention, the method comprises the steps of: i) injecting a monomer into the monomer injection port (1b), and injecting a continuous phase into the continuous phase injection port (1a); Ii) the monomer and the continuous phase pass through the junction point (2a) of the continuous phase and the monomer to form monomer droplets; Iii) discharging the monomer droplets through the fine passage (2) and through the outlet (2b); And iii) the monomer droplets are cured in real time by the ultraviolet irradiation means 6 to produce microbeads, wherein the ultraviolet irradiation of the iii) step is directed to the outlet 2b vertically downward. When the monomer droplets are discharged, the ultraviolet rays are completely cured in real time by irradiating ultraviolet rays, or the ultraviolet ray irradiation in the step iii) is performed by irradiating the ultraviolet rays when the monomer droplets move below the discharge port 2b. Or it is more desirable to produce microbeads having a diameter larger than the width.

In addition, in the polymer microbead production method of the present invention, the continuous phase and the monomer injected into the inlet (1a, 1b) of the respective fluids, first to prevent the monomer is adsorbed to the fine flow path (2) It is more preferable to inject the monomer after completely filling the micro-channel 2, and the monomer is more preferably a precursor of polyurethane, the continuous phase is an aqueous solution of sodium dodecyl sulfate (SDS), the monomer Is most preferably NOA63 (Norland optical adhesive 63) diluted in acetone.

In addition, in the polymer microbead manufacturing method of the present invention, it is more preferable to control the size of the finally obtained microbeads in real time by adjusting the volume flow rate of the fluid injected through the inlet (1a, 1b) of each fluid.

Hereinafter, the present invention will be described in detail with reference to the accompanying drawings.

According to a feature of the present invention for achieving the object as described above, as shown in Figure 1, through the soft lithography process of the continuous injection hole (1a) and the monomer located above the microfluidic chip made of a transparent elastic polymer The two fluids injected through the injection port 1b meet at the junction point 2a of the continuous phase and the monomer to form a droplet of spherical shape. The monomer droplets thus formed are moved through the microchannel 2 by the flow of the continuous phase, and discharged to the tank 5 in which the continuous phase 4 is filled through the discharge port 2b facing in the vertical downward direction. . At this time, as the monomer droplet moves vertically downward through the space secured by the microbead manufacturing apparatus support 3, the speed in the horizontal direction is significantly reduced, which provides sufficient time for irradiating ultraviolet rays. Therefore, the monomer droplets discharged through the discharge port 2b are solidified by the ultraviolet irradiation means 6 before reaching the bottom of the water tank 5 to become a fully cured microbead 7 without a separate post irradiation process.

When the volume flow rate of the monomer injected into the microfluidic chip 100 is increased by a predetermined amount or more, the monomer droplets formed in the microfluidic channel 2 become a plug shape in which the microchannel 2 is tightly closed instead of a perfect sphere. Thus formed plug-shaped monomer droplets are discharged through the discharge port, the shape of the droplets are changed back to the spherical droplets by the surface tension in the tank (5) relatively wider than the fine passage (2). Thus, the monomer droplet changed into the spherical shape moves downward by gravity, and is completely cured by the ultraviolet irradiation means 5 in real time. Therefore, a fully cured polymer microbead having a diameter larger than the height or width of the microchannel 2 by the microbead manufacturing apparatus using the microfluidic chip 100 of the present invention is also real-time. It is possible to manufacture with.

To demonstrate this, the inventors fabricated the microfluidic chip 100 for microbead manufacturing, placing it in a tank 5 filled with a continuous phase 4 and pointing downwardly to the outlet 2b and the bottom of the tank 5. In order to create a space between the microfabrication base (3) made of a piece of glass substrate was placed between the outlet (2b) and the water tank (5) to finally produce a microbead manufacturing apparatus.

The monomer and the continuous phase were injected into the prepared microfluidic chip 100 through the respective injection holes 1a and 1b. At this time, in order to prevent the monomer from being adsorbed on the fine flow path (2), the continuous phase was first injected, and the fine flow path (2) was completely filled into the continuous phase, and then the monomer was injected. The injected continuous phase aqueous solution and the monomer meet at the junction point 2a of the continuous phase and the monomer, and droplets of the spherical monomer are formed in the continuous phase due to their incompatibility. The monomer droplet thus formed is moved through the fine flow path 2 in accordance with the flow of the continuous phase, and is discharged through the discharge port 2b facing in the vertical downward direction. The discharged monomer droplets are moved downward through the space filled with the continuous phase. At this time, since the velocity in the horizontal direction is significantly reduced, the polyurethane is completely cured before the monomer droplets reach the bottom of the water tank by irradiating ultraviolet rays. Micro beads can be prepared. The prepared polyurethane microbeads do not cause coalescence between the beads because the polyurethane beads are completely cured (see FIG. 3). In addition, the dispersion degree of the polyurethane microbeads is about 1%, so that the size of the polyurethane microbeads produced by the present invention is very uniform (see FIG. 4). In addition, the surface structure of the polyurethane microbead prepared according to the present invention was confirmed that the particles have a round sphere shape (see Fig. 5).

In addition, as a result of observing the correlation between the injected continuous phase and the flow rate of the monomer and the diameter of the microbeads, the size of the microbeads produced by adjusting the volume flow rate of the two fluids introduced into the microfluidic chip 100 in real time It can be adjusted (see FIG. 6).

In the microbead manufacturing apparatus of the present invention, the microfluidic chip is placed in a water tank containing a continuous phase, and the outlet of the fluid is positioned at the bottom of the microfluidic chip so that the monomer droplets generated in the microfluidic chip are discharged downward through the outlet. The monomer droplets are irradiated with ultraviolet light while being moved downward by gravity in a continuous water-containing bath to produce fully cured polymer microbeads in real time. As described above, the microbead manufacturing apparatus of the present invention can significantly increase the UV irradiation time for the photocurable polymer droplets exiting through the outlet by applying a fluid outlet directed vertically downward to the microfluidic chip. As a result, even monomers requiring relatively long UV irradiation time can be produced in real time in microfluidic chips, and even when the flow velocity of the fluid is rapidly increased, fully cured polymer beads can be obtained in real time. In production, the production of polymer microbeads can be dramatically increased.

Hereinafter, with reference to the accompanying drawings a preferred embodiment of the microbead manufacturing apparatus and a manufacturing method using the same according to the present invention having the configuration as described above will be described in detail. However, the following examples are only for illustrating the present invention, and the present invention is not limited to the following examples and may be changed to other embodiments equivalent to substitutions and equivalents without departing from the technical spirit of the present invention. Will be apparent to those of ordinary skill in the art.

Example 1 Fabrication of Micro Bead Manufacturing Device Including Microfluidic Chip

The negative photosensitive agent (SU-8) was evenly coated on the silicon wafer, and then spin-coated at 1,000 rpm to raise a 100 μm high photosensitive agent. UV was irradiated through a mask having a microfluidic shape to prepare a master mold having a shape opposite to that of the channel. Thereafter, the PDMS was poured into the prepared master mold and cured in an oven to produce a PDMS mold having a microchannel having a desired shape. The microfluidic chip 100 was manufactured by attaching a glass substrate previously drilled to the PDMS mold thus prepared through oxygen plasma treatment. The microfluidic chip 100 was placed in a bath 5 filled with a continuous phase 4 prepared in advance. At this time, in order to make a space between the outlet 2b facing downwards and the bottom of the water tank 5, a micro manufacturing apparatus support 3 made of a piece of glass substrate is placed between the water outlet 2b and the water tank 5 and finally, The microbead manufacturing apparatus was produced.

Example 2 Injection of Monomer and Continuous Phase Using a Syringe Pump

The tank containing the microfluidic chip 100 manufactured in Example 1 was placed on a microscope stage (NIKON, T2000-U, Japan), and a syringe and a continuous phase were passed through a Tygon tube using a syringe pump. , Through the respective injection ports (1a, 1b). In order to prevent the monomer from adsorbing to the fine flow path (2), first, a continuous aqueous solution of sodium dodecyl sulfate (SDS) was injected, and the precursor of the polyurethane as a monomer was used as the monomer after the fine flow path (2) was completely filled with the aqueous SDS solution. A solution obtained by diluting NOA63 (Norland optical adhesive 63), which is an adhesive solidified by ultraviolet rays, to acetone at 70% was injected.

Example 3 Preparation of Polyurethane Beads by UV Irradiation

The SDS aqueous solution and NOA63 injected in Example 2 meet at the junction point 2a of the continuous phase and the monomer, and due to the non-mixing property, droplets of the spherical NOA63 form in the continuous SDS aqueous solution. The NOA63 droplets thus formed were moved through the micro flow path 2 according to the flow of the SDS aqueous solution, and discharged through the outlet 2b facing in the vertical downward direction. The discharged NOA63 droplets are moved downward through the space filled with SDS aqueous solution. At this time, since the speed in the horizontal direction is significantly decreased, the NOA63 droplets are irradiated with ultraviolet rays through the UV irradiation device, so that the NOA63 droplets are at the bottom of the tank (5). Fully cured polyurethane microbeads could be prepared before contacting. As a result of observing the photomicrographs of the obtained polyurethane microbeads, it was confirmed that the polyurethane beads were completely cured so that no coalescence occurred between the beads (FIG. 3). Polyurethane microbeads were also measured for dispersion using an image analysis program (FIG. 4). As a result, since the measured dispersion degree was about 1%, it was confirmed that the size of the polyurethane microbeads produced by the present invention was very uniform. In addition, the surface structure of the polyurethane microbead prepared by the present invention was confirmed through a scanning electron microscope (Fig. 5). As a result, it was confirmed that the particles produced by the present invention were micro beads having a round sphere shape.

Example 4 Control of Flow Rate of Fluid for Size Control of Micro Beads

In order to control the size of the polyurethane beads prepared in Example 3, the flow rates of the SDS aqueous solution and NOA63 were adjusted. The correlation between the flow rate of the continuous phase and the monomer injected and the diameter of the microbeads was observed (FIG. 6).

Specifically, in the effect experiment on the volume flow rate of the SDS aqueous solution used in the continuous phase, the size of the polyurethane beads produced by changing the volume flow rate of the continuous phase in the NOA63 conditions of the same flow rate was adjusted. The volume of NOA63 supplied per unit time decreases as the volumetric flow rate of the SDS aqueous solution increases, thus reducing the size of the NOA63 droplets formed in the microfluidic chip. As a result, the size of the finally produced polyurethane microbeads decreases with increasing volume flow rate of the SDS aqueous solution. On the contrary, when the volumetric flow rate of NOA63 was increased in the SDS aqueous solution at the same flow rate, the volume of NOA63 supplied per unit time was increased, thereby increasing the final bead size. The experiment confirmed that the size of the microbeads produced can be adjusted in real time by adjusting the volume flow rates of the two fluids introduced into the microfluidic chip 100.

1 is a cross-sectional view of a microbead manufacturing apparatus according to an embodiment of the present invention.

2 is an exploded perspective view of a microbead manufacturing apparatus according to an embodiment of the present invention.

3 is an enlarged photograph of the microbeads manufactured using the microbead manufacturing apparatus according to the embodiment of the present invention.

Figure 4 is a dispersion graph showing the uniformity of the microbeads manufactured using the microbead manufacturing apparatus according to an embodiment of the present invention.

Figure 5 is a scanning electron microscope (Scanning Electron Microscope) photograph showing the surface structure of the microbead prepared using the microbead manufacturing apparatus according to an embodiment of the present invention.

6 is a graph showing the correlation between the flow rate of the monomer and the diameter of the microbeads and the continuous phase injected.

<Description of the symbols for the main parts of the drawings>

100: microfluidic chip, 1a: continuous phase inlet,

1b: monomer injection port, 2: fine flow path,

2a: junction of continuous phase and monomer, 2b: outlet,

3: micro bead manufacturing apparatus support, 4: continuous phase,

5: water tank, 6: ultraviolet irradiation means

Claims (14)

A microfluidic chip comprising a monomer inlet 1b, a continuous phase inlet 1a, a junction point 2a of a continuous phase and a monomer, a microchannel 2 and an outlet 2b, a water tank 5, and the outlet 2b. In order to increase the time until the monomer droplets discharged through the bottom of the water tank (5), it comprises a micro bead manufacturing apparatus support (3) which is directed vertically downward to the bottom of the microfluidic chip, Monomer injected into the monomer inlet 1b passes through the junction point 2a of the continuous phase and the monomer, and monomer droplets formed through the micro-channel 2 are directed downward to increase the ultraviolet irradiation time 2b. Microbead production apparatus characterized in that the polymer microbeads are manufactured by completely curing in real time by ultraviolet irradiation means (6) while being discharged through. delete The method of claim 1, The water tank (5) is a microbead manufacturing apparatus, characterized in that the continuous phase (4) is contained in order to make the conditions inside and outside the microfluidic chip at the boundary of the outlet (2b). delete The method of claim 1, Micro-bead manufacturing apparatus, characterized in that the monomer injection port (1b) and the continuous phase injection port (1a) each composed of two. A method for producing polymeric microbeads using the apparatus for producing microbeads according to claim 1 or 3. The method of claim 6, The manufacturing method, Iii) injecting the monomer into the monomer inlet 1b and injecting the continuous phase into the continuous-phase inlet 1a; Ii) the monomer and the continuous phase pass through the junction point (2a) of the continuous phase and the monomer to form monomer droplets; Iii) discharging the monomer droplets through the fine passage (2) and through the outlet (2b); And Iii) a method of producing polymer microbeads, wherein the monomer droplets are cured in real time by ultraviolet irradiation means (6) to produce microbeads. The method of claim 7, wherein Ultraviolet irradiation in the step iii) is a method for producing polymer microbeads, characterized in that the monomer droplets are completely cured by irradiating ultraviolet rays when the monomer droplets are discharged to the outlet (2b) facing vertically downward. The method of claim 7, wherein The ultraviolet irradiation in the step iii) produces a microbead having a diameter larger than the height or width of the microchannel 2 by irradiating ultraviolet rays when the monomer droplet is moved below the outlet 2b. Manufacturing method. The method of claim 7, wherein The monomer and the continuous phase injected into the injection ports 1a and 1b of the respective fluids first completely fill the microchannel 2 with the continuous phase in order to prevent the monomer from being adsorbed onto the microchannel 2. Polymer microbeads manufacturing method characterized in that the injection. 8. The method of claim 7, wherein the continuous phase is an aqueous solution of sodium dodecyl sulfate (SDS). The method of claim 7, wherein The monomer is a polymer microbead production method, characterized in that the precursor of the polyurethane is a main component. The method of claim 12, wherein the monomer is NOA63 (Norland optical adhesive 63). The method of claim 7, wherein Polymer microbeads manufacturing method characterized in that to control in real time the size of the finally obtained microbeads by adjusting the volume flow rate of the fluid injected through the inlet (1a, 1b) of each fluid.

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