KR102591957B1 - Microfluidic device including fibrous microfluidic channel, manufacturing method thereof, and manufacturing method of microdroplets - Google Patents

Abstract

The present invention has a structure in which a first layer, a second layer, and a third layer are stacked top and bottom in that order, wherein the first layer includes a first injection port through which an oily material is injected; a second injection port through which an aqueous substance is injected; and an outlet for discharging microdroplets, wherein the second layer includes a fibrous microfluidic channel, and the third layer is a layer supporting the second layer, and the fibrous microfluidic channel It relates to a microfluidic device, which is a channel through which the oil-phase material and the aqueous-phase material flow to form micro-droplets, a method of manufacturing the same, and a method of manufacturing micro-droplets.

Description

Microfluidic device including a fibrous microfluidic channel, a manufacturing method thereof, and a manufacturing method of microdroplets

The present invention relates to a microfluidic device, a method of manufacturing the same, and a method of manufacturing microdroplets. Specifically, it relates to a microfluidic device including a fibrous microfluidic channel, a method of manufacturing the same, and a method of manufacturing microdroplets.

Microfluidic devices are a platform for analysis, consuming less reagents, and are portable, convenient, and highly sensitive for various experiments such as detection of viruses or tumor cells, biosensors, protein crystallization, material synthesis, sample injection, and production of polymer microparticles. It has the advantage of being able to implement . In particular, the microfluidic device can generate uniform droplets of two immiscible liquid phases in various ways while controlling monodisperse emulsions and micro-sized particles, and the microfluidic device can produce uniform droplets of micrometer size. It is attracting attention in various application fields that require single beads, such as cosmetics, coatings, drug delivery, and tissue engineering.

The microfluidic device is generally manufactured through 3D printing, soft lithography, and microcapillary assembly.

3D printing has the advantage of being an easy and simple process and low cost, but it has the limitation of producing micro droplets with relatively large particle sizes because it is difficult to fabricate micro channels with a diameter of 100 μm or less. . On the other hand, soft lithography has the advantage of producing smaller droplets with high reproducibility and precision by creating precise nano- or micro-sized channels by forming a desired geometric pattern with ultraviolet rays on a photoresist substrate. , the process was relatively complex and there were limitations to process operation due to the expensive equipment required for the process. In addition, when producing micro-droplets such as emulsions using a microfluidic device having a single channel manufactured using the existing method described above, there was a limitation in that mass production was difficult and productivity was low.

Republic of Korea Patent Publication No. 10-2021-0031217 “Microdroplet-based microfluidic chip and its uses”

(Paper 1) Attoliter protein nanogels from droplet nanofluidics for intracellular delivery, Science Advances　　07 Feb 2020: Vol. 6, no. 6, eaay7952 (DOI: 10.1126/sciadv.aay7952)

In order to solve the above problem, the present inventors applied a microfluidic device containing a large number of fiber-type microfluidic channels within a limited area, where oily substances and aqueous substances that are difficult to mix easily meet to form microfluidic substances such as emulsions of various particle sizes. The aim is to provide a microfluidic device capable of producing droplets in large quantities, a manufacturing method thereof, and a method for manufacturing microdroplets.

According to the first aspect of the present invention,

It has a structure in which a first layer, a second layer, and a third layer are stacked top and bottom in that order, wherein the first layer includes a first injection port through which an oily material is injected; a second injection port through which an aqueous substance is injected; and an outlet for discharging microdroplets, wherein the second layer includes a fibrous microfluidic channel, and the third layer is a layer supporting the second layer, and the fibrous microfluidic channel Provides a microfluidic device, which is a channel through which the oil phase material and the water phase material flow to form micro droplets.

In one embodiment of the present invention, the fiber-type microfluidic channel may include one selected from the group consisting of microfiber-type channels, nanofiber-type channels, and combinations thereof.

In one embodiment of the present invention, the first layer includes a first flow path through which an oily substance moves; and a second flow path through which the aqueous material moves, wherein each discharge portion of the first flow path and the second flow path may be located in a junction area where the oily material and the aqueous material meet.

In one embodiment of the present invention, the first layer further includes a third flow path connected to the outlet for movement of microdroplets, and the inlet of the third flow path corresponds to the position of the microfluidic channel of the second layer. It can be located as follows.

In one embodiment of the present invention, the second layer has a fibrous microfluidic channel at a position corresponding to the junction area of the first layer where the oily material and aqueous material moving through the first flow path and the second flow path meet. It can be included.

In one embodiment of the present invention, the third layer may include a polydimethylsiloxane layer.

In one embodiment of the present invention, the fibrous microfluidic channel may have a diameter of 20 μm or less.

According to the second aspect of the present invention,

(1) producing a fiber body by electrospinning a polymer solution; (2) manufacturing a second layer including a fibrous microfluidic channel using the electrospun fiber body; (3) manufacturing the first layer using 3D printing; and (4) bonding the first layer to the top of the second layer and bonding the third layer supporting the second layer to the bottom.

In one embodiment of the present invention, step (1) may include electrospinning the polymer solution at a flow rate of 0.01 to 0.50 mL/min and a voltage of 5 to 30 kV.

In one embodiment of the present invention, in step (2), the electrospun fiber is impregnated in a solution containing polydimethylsiloxane, the polydimethylsiloxane is cured, and the fiber is dissolved in an organic solvent. It may include forming a fibrous microfluidic channel.

In one embodiment of the present invention, step (3) includes a first injection port through which an oily substance is injected; a second injection port through which an aqueous substance is injected; and an outlet for discharging fine droplets formed when the oily material and the aqueous material meet. It may include manufacturing a first layer including a 3D printing method.

According to the third aspect of the present invention,

A method for producing micro-droplets is provided, including the step of generating micro-droplets by injecting an oil-phase material and an aqueous-phase material into the microfluidic device.

The microfluidic device according to the present invention, unlike existing microfluidic devices composed of a single channel, has a large number of fibrous microfluidic channels formed by using polymer fibers produced through an electrospinning process as a template within a limited area. When manufacturing particles such as emulsions, production speed is improved and mass production is possible, thereby improving productivity.

In addition, in the microfluidic device according to the present invention, the type of fluid that can be injected into the microfluidic channel is not limited, so it is possible to produce not only emulsions but also various microdroplets, and the diameter and oily material of the microfluidic channel included in the microfluidic device It has the advantage of being able to mass-produce microdroplets of various sizes suitable for each use and purpose by controlling the flow rate.

Figure 1 shows a schematic diagram of a microfluidic device in the present invention.
Figure 2 is a scanning electron microscope (SEM) image of the electrospun fiber and the fibrous microfluidic channel (diameter 12μm, 9μm, 6μm) formed using the electrospun fiber as a template in the present invention. It's a photo.
Figure 3 is a photograph taken with a confocal microscope after injecting an aqueous solution containing a fluorescent dye into a fibrous microfluidic channel formed using an electrospun fiber as a template in the present invention.
Figure 4 shows that in the present invention, the microfluidic device containing a fibrous microfluidic channel (diameter 12μm, 9μm, 6μm) formed using electrospun fibers as a template is injected through a syringe pump. This is a photograph of emulsion particles according to the flow rate of the oily substance.
Figure 5 shows the size of the emulsion particles generated while controlling the flow rate of the oily material through a microfluidic device including a fibrous microfluidic channel (diameter 12 μm) formed using electrospun fibers as a template in the present invention. This is a graph showing the coefficient of variation (CV) measured.
Figure 6 shows the size of the emulsion particles generated while controlling the flow rate of the oily material through a microfluidic device including a fibrous microfluidic channel (9 μm in diameter) formed using electrospun fibers as a template in the present invention. This is a graph showing the coefficient of variation (CV) measured.
Figure 7 shows the size of the emulsion particles generated while controlling the flow rate of the oily material through a microfluidic device including a fibrous microfluidic channel (diameter 6 μm) formed using electrospun fibers as a template in the present invention. This is a graph showing the coefficient of variation (CV) measured.

The embodiments provided according to the present invention can all be achieved by the following description. It should be understood that the following description describes preferred embodiments of the present invention, and that the present invention is not necessarily limited thereto.

microfluidic device

As shown in Figure 1, the microfluidic device according to the present invention has a structure in which a first layer, a second layer, and a third layer are stacked in the order of top and bottom, and the first layer is a first injection port through which the oily material is injected. ; a second injection port through which an aqueous substance is injected; and an outlet for discharging microdroplets, wherein the second layer includes a fibrous microfluidic channel, and the third layer is a layer supporting the second layer, and the fibrous microfluidic channel is a channel through which the oil phase material and the water phase material flow to form fine droplets.

The oily material injected through the first inlet of the first layer and the aqueous material injected through the second inlet may meet through the fibrous microfluidic channel existing in the second layer to form micro droplets. The fibrous microfluidic channel is based on electrospun fibers. Specifically, the electrospun fibers are impregnated in a mixed solution of polydimethylsiloxane (PDMS, Polydimethylsiloxane) and a curing agent, and then the polydimethylsiloxane is cured and dichlorolyzed. A fibrous microfluidic channel may be formed as shown in FIG. 3 by removing the electrospun polymer fiber by placing it in an organic solvent such as methane (DCM, Dichloromethane).

In this specification, a 'template' is used to manufacture a fibrous microfluidic channel and can be defined as a membrane-shaped structure formed by randomly entangling polymer fibers.

In this specification, the 'fiber-type microfluidic channel' may be defined as a fiber-type microfluidic channel including a microfluidic channel formed using the template, specifically, the electrospun fiber body as a team plate.

The fiber-type microfluidic channel may include one selected from the group consisting of microfiber-type channels, nanofiber-type channels, and combinations thereof. The microfiber-shaped channel may include a microchannel having a diameter ranging from several micrometers (μm) to hundreds of micrometers (μm), and the nanofiber-type channel may include a microchannel having a diameter ranging from several tens of nanometers (nm) to hundreds of nanometers (nm). ) may include a nanochannel with a diameter of the size. The diameter of the microfluidic channel can be controlled using process variables during electrospinning, and can be designed to match the particle size and particle production volume when manufacturing microdroplets.

The fibrous microfluidic channels are 20μm or less, 19μm or less, 18μm or less, 17μm or less, 16μm or less, 15μm or less, 14μm or less, 13μm or less, 12μm or less, 11μm or less, 10μm or less, 9μm or less, 8μm or less, 7μm or less, 6μm or less. It may have a diameter of 5 μm or less, 4 μm or less, 3 μm or less, 2 μm or less, or 1 μm or less. In a conventional microfluidic device with a single channel, for example, a microfluidic device including a channel manufactured through a soft lithography process, when the diameter of the channel is 20 μm or less, a high pressure is applied when the fluid flows through a pump, causing the fluid to flow. There was a limit where the flow of was limited. On the other hand, the present invention manufactures a fibrous microfluidic channel formed using an electrospun fiber as a template, and has a channel with a diameter of 20 μm or less, but the presence of multiple channels can reduce the pressure applied to the channel, It is effective in producing fine droplets of 1μm or less.

The microfluidic channel of the second layer may include a microchannel or nanochannel formed using electrospun microfibers or nanofibers as a template.

In this specification, 'channel' may be defined as a space that can contain microfluidic.

As shown in Figure 1, the first layer includes a first flow path through which an oily substance moves; and a second flow path through which the aqueous material moves, wherein each discharge portion of the first flow path and the second flow path may be located in a junction area where the oily material and the aqueous material meet. Additionally, the second layer may include a fibrous microfluidic channel at a position corresponding to the junction area of the first layer where the oil-phase material and aqueous-phase material moving through the first flow path and the second flow path meet.

The oily material injected through the first injection port may move along the first flow path and reach the junction area where the end of the flow path is located, and the aqueous material injected through the second injection port may move along the second flow path. It can reach the junction area where the end of the flow path is located. After the oily and aqueous substances moved along each channel reach the junction area, they meet in the 'fibrous microfluidic channel formed using electrospun fibers as a template' located in the second layer to form an emulsion. It is possible to form fine droplets such as .

As shown in FIG. 1, the first layer further includes a third flow path connected to the outlet for the movement of fine droplets, and the inlet of the third flow path is located at the location of the fibrous microfluidic channel of the second layer. It can be located correspondingly. Specifically, in order for microdroplets to move, the fibrous microfluidic channel and the inlet portion of the third flow path may be directly connected.

The micro droplets may be obtained from the fibrous microfluidic channel, then flow in and move through the inlet portion of the third flow path, and be discharged from the microfluidic device through the discharge portion.

The third layer may include a polydimethylsiloxane layer. The third layer may include a polydimethylsiloxane layer that does not include fibrous microfluidic channels to prevent outflow of fluid. The third layer is coupled to the lower part of the second layer and may serve to prevent fluid from leaking from the second layer.

Manufacturing method of microfluidic device

The method for manufacturing a microfluidic device according to the present invention includes the steps of (1) producing a fiber body by electrospinning a polymer solution; (2) manufacturing a second layer including a fibrous microfluidic channel using the electrospun fiber body; (3) manufacturing the first layer using 3D printing; and (4) bonding the first layer to the top of the second layer and bonding the third layer supporting the second layer to the bottom.

(1) Step of producing a fiber body by electrospinning a polymer solution

The method for manufacturing the microfluidic device includes manufacturing a fiber body by electrospinning a polymer solution.

In step (1), after preparing a polymer solution to produce an electrospun fiber, the polymer solution is injected into a syringe, a voltage is applied to the dust collection plate while maintaining a certain distance between the current collector plate and the needle, and the syringe is Fibers can be manufactured by spinning by operating the pump.

The polymer included in the polymer solution in step (1) may be a polymer that can be dissolved in an organic solvent. For example, dichloromethane may be used to form a fibrous microfluidic channel using electrospun fibers as a template. It may be a polymer that can be dissolved in an organic solvent such as (DCM). The polymer that can be dissolved in the organic solvent is preferably poly(ε-caprolactone), polylactic acid (PLA), polylactic-co-glycolic acid (PLGA), A group consisting of poly(lactic-co-glycolic acid), poly(ethylene oxide) (PEO), polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), and combinations thereof. It may contain a polymer selected from, and more preferably, it may contain poly(ε-caprolactone) as the polymer, but is not particularly limited as long as it is a polymer that can be dissolved in an organic solvent.

In addition, the polymer contained in the polymer solution in step (1) may be a polymer that can be dissolved in water. For example, the polymer may be dissolved in water to form a fibrous microfluidic channel using electrospun fibers as a template. It can be a polymer that can be The water-soluble polymer is preferably polymer polysaccharide, alginate, chitosan, hyaluronic acid, heparin, gelatin, starch, polyarginine, polylysine, polyethylene glycol, polypropylene glycol, polyethylene oxide, polyvinylpyrrolidone, It may include a polymer selected from the group consisting of polyvinyl alcohol and combinations thereof, but is not particularly limited as long as it is a polymer that can dissolve in water.

The polymer solution is a 5 to 20% concentration, preferably a 10 to 17.5% concentration, more preferably a 15 to 17.5% concentration of the polymer in a mass ratio of chloroform and alcohol (methanol or ethanol) of 1:1 to 6:1. It can be prepared by dissolving in a mixed solution.

The flow rate of the polymer solution moved by the syringe pump is 0.01 mL/min or more, 0.02 mL/min or more, 0.03 mL/min or more, 0.04 mL/min or more, 0.05 mL/min or more, 0.06 mL/min or more, 0.07 It can be more than mL/min, 0.08 mL/min or more, 0.50 mL/min or less, 0.47 mL/min or less, 0.44 mL/min or less, 0.41 mL/min or less, 0.38 mL/min or less, 0.35 mL/min or less, 0.32 mL/min or less, 0.29mL/min or less, 0.26mL/min or less, 0.23mL/min or less, 0.20mL/min or less, 0.18mL/min or less, 0.16mL/min or less, 0.14mL/min or less, 0.12mL/ min or less, 0.10 mL/min or less, 0.09 mL/min or less, and 0.08 mL/min or less. Additionally, the voltage applied to the dust collection plate during electrospinning may be 5kV or higher, 5.5kV or higher, 6kV or higher, 6.5kV or higher, 7kV or higher, 7.5kV or higher, 8kV or higher, and 30kV or lower, 28kV or lower, 26kV or lower, 24kV or lower, and 22kV. It may be 20kV or less, 18kV or less, 16kV or less, 14kV or less, 13kV or less, 12kV or less, and 11kV or less.

During the above electrospinning, the diameter of the electrospun fiber can be adjusted by controlling the flow rate of the polymer solution through the syringe pump and the voltage intensity of the dust collection plate. Specifically, as the flow rate of the syringe pump decreases, the amount of polymer solution at the tip of the needle decreases, and as the strength of the voltage increases, the repulsive force of the charges collected in the Taylor cone becomes stronger, and small-diameter fibers are manufactured through electrospinning. It can be. Conversely, as the flow rate of the syringe pump increases, the amount of polymer solution at the tip of the needle increases, and as the voltage intensity decreases, the repulsion of charges collected in the Taylor cone weakens, allowing large-diameter fibers to be manufactured through electrospinning.

(2) manufacturing a second layer containing a fibrous microfluidic channel using the electrospun fiber body

The method of manufacturing the microfluidic device includes manufacturing a second layer including a fibrous microfluidic channel using the electrospun fiber body.

Step (2) is a step of impregnating the electrospun fiber in a solution containing polydimethylsiloxane, curing the polydimethylsiloxane, and dissolving the fiber in an organic solvent to form a fibrous microfluidic channel. may include.

Specifically, in step (2), a solution of polydimethylsiloxane (PDMS) and a curing agent is poured onto the electrospun fiber produced through step (1), and then cured, and then cured with dichloromethane (DCM). This may be a step of removing the fibers by immersing them in the same organic solvent, and the fibers to be removed may be in the form of a membrane of fibers formed by randomly entangling fibers. When the fiber body is removed through the organic solvent, a fibrous microfluidic channel with a thickness of the diameter of the fiber body may be formed in the space where the fiber body was. The method for forming a fibrous microfluidic channel of the present invention has the advantage of being able to fabricate a nanometer or micrometer level channel in a short period of time and at low cost.

The second layer can be manufactured in a simple and highly reproducible manner in the laboratory using a slide glass, double-sided tape, and cover glass.

(3) manufacturing the first layer using 3D printing

The method of manufacturing the microfluidic device includes manufacturing the first layer using 3D printing.

In step (3), the oily material and the aqueous material are injected and moved, and the positions and paths through which the fine droplets formed through the fiber-type microfluidic channel move and are discharged are 3D printed on a slide glass in a pattern, thereby forming the first layer. It can be manufactured.

Specifically, step (3) includes a first injection port through which an oily substance is injected; a second injection port through which an aqueous substance is injected; and an outlet for discharging fine droplets formed when the oily material and the aqueous material meet. It may include manufacturing a first layer including a 3D printing method.

In step (3), a pattern including the first inlet, second inlet, first to third paths, and outlet can be 3D printed on a slide glass using a 3D printer using a polymer solution. Afterwards, a curing agent solution containing polydimethylsiloxane was poured onto a glass slide, cured, and then immersed in an organic solvent to remove the polymer to form a first layer in which channels through which oily substances, aqueous substances, and fine droplets could be injected, moved, and discharged were formed. It can be manufactured.

(4) combining the first to third layers to manufacture a microfluidic device

The method of manufacturing the microfluidic device includes bonding a first layer to the top of the second layer and bonding a third layer supporting the second layer to the bottom.

The fibrous microfluid of the second layer is located at a location corresponding to the junction area where the 'discharge portions located at the ends of the first flow path and the second flow path' and the 'fine droplet inlet portion of the third flow path' of the first layer are located. The first layer and the second layer can be combined so that the channel is located. After the bonding, a third layer supporting the bonded first to second layers can be bonded to the bottom of the second layer to manufacture a microfluidic device.

The third layer is coupled to the lower part of the second layer and may serve to prevent fluid from leaking from the second layer. The polydimethylsiloxane coating layer may serve to prevent fluid from leaking.

Method for producing fine droplets

The method for producing micro-droplets of the present invention may include the step of generating micro-droplets by injecting an oil-phase substance and an aqueous-phase substance into the microfluidic device.

The oily material injected into the first inlet of the microfluidic device to generate microdroplets is a continuous oily material, and is not particularly limited as long as it is an oily material that does not expand the polydimethylsiloxane used during curing.

The aqueous material injected into the second inlet of the microfluidic device is also not particularly limited as long as it is a discontinuous aqueous material.

The continuous phase, an oily material, and the discontinuous phase, an aqueous phase, may meet in a fibrous microfluidic channel in a microfluidic device to form micro droplets. An example of the micro droplets may be an emulsion.

Since the microfluidic device includes a plurality of fibrous microfluidic channels formed by melting electrospun fibers, the oily material and the aqueous material meet with a high probability of generating microdroplets compared to existing single-channel microfluidic devices. It can be done, and mass production may also be possible. In particular, when electrospinning fibers before manufacturing fibrous microfluidic channels, it is possible to manufacture fibers with various diameters by adjusting the flow rate and voltage, and through this, the diameter of the fibrous microfluidic channels can be adjusted. Additionally, when injecting an oily material into a microfluidic device, fine droplets of various particle sizes can be formed by controlling the flow rate.

Hereinafter, preferred examples are presented to aid understanding of the present invention, but the following examples are provided to facilitate understanding of the present invention and do not limit the present invention thereto.

Example: Microfluidic device including a fiber-type microfluidic channel

[Example 1]

(1) Step of producing a fiber body by electrospinning a polymer solution

Mix chloroform (Sigma-Aldrich, 288306-2L) and 2,2,2-trifluoroethanol (2,2,2-Trifluoroethanol) (Sigma-Aldrich, T63002-500G) at a mass ratio of 4:1. 1.5 g of poly(ε-Caprolactone) (Sigma-Aldrich, 440744-500G, Mn=70000 to 90000) was dissolved in the solution to prepare a poly(ε-caprolactone) polymer solution. Manufactured.

After injecting the polymer solution into the syringe, the syringe is shaped into a horizontal yarn, and while maintaining the distance between the dust collection plate and the spraying needle at 15 cm, it is spun through a syringe pump, and at the same time, a voltage of 9 kV is applied to form fibers on the dust collection plate. Manufactured. At this time, the flow rate of the polymer solution was 0.10 mL/min, and an 18 gauge needle was used. A circular punch with a diameter of 5 mm was drilled on the prepared fiber body to prepare a circular fibrous membrane.

(2) manufacturing a second layer containing fibrous microfluidic channels using electrospun fibers

A polydimethylsiloxane solution was prepared by mixing polydimethylsiloxane elastomer and a curing agent (Sewang Hitech, SYLGARD 184 Base&Curing Agent) at a mass ratio of 10:1.

On the edge of the acrylic plate, three slide glasses were stacked with double-sided tape, and a cover glass was attached to the top with double-sided tape to create a lower plate structure. The fibrous body membrane was placed in the center of the acrylic plate, the polydimethylsiloxane solution prepared above was poured, and the lower plate structure was pressed into a separate upper plate structure composed of a slide glass and an acrylic plate. After pressing, it was cured in an oven at 60°C for 5 hours.

After separating the polydimethylsiloxane cured material containing the cured fibrous membrane with a thickness of 400 μm from the upper plate structure and the lower plate structure, the cured material is soaked in dichloromethane for 1 hour to form the fibrous body in the cured material. The membrane was melted to prepare a second layer (3 cm x 5 cm) containing a fibrous microfluidic channel.

(3) manufacturing the first layer using 3D printing

Poly(ε-Caprolactone) (Sigma-Aldrich, 440744-500G, Mn=14000) was printed on a 3D printer (3D Printer, EzROBO-5 GX ST 2520, Eugene Technology, Korea) at 80°C. After melting in a barrel, it is printed at a speed of 4 mm/sec, and under the condition of injecting the solution at 500 kPa, an injection port (first injection port) and flow path (first flow path) for the oily material, and an injection port for the aqueous material are placed on the glass slide as shown in Figure 1. It was 3D printed on a slide glass with a pattern including (second inlet) and flow path (second flow path), emulsion flow path (third flow path), and emulsion outlet (outlet).

After setting up a slide glass in a shape surrounding the printed slide glass, a polydimethylsiloxane solution was poured and cured. After separating the cured product from the slide glass, it is soaked in dichloromethane for 1 hour to dissolve the poly(ε-caprolactone) formed along the pattern and to create a solution through which oily substances, aqueous substances, and emulsions can be injected, moved, and discharged. A first layer forming channels was prepared.

(4) combining the first to third layers to manufacture a microfluidic device

The second layer was combined so that the position of the microfluidic channel corresponded to the area where the distal end of the first flow path, the distal end of the second flow path, and the injection part of the third flow path of the first layer were joined.

In addition, a third layer was prepared by applying a polymethylsiloxane solution on a glass slide and curing it, and then bonding it to the bottom of the second layer to finally manufacture a microfluidic device.

[Example 2]

A microfluidic device was manufactured in the same manner as in Example 1, except that a voltage of 7 kV was applied to the dust collection plate when manufacturing the fiber, and the flow rate of the polymer solution was adjusted to 0.10 mL/min.

[Example 3]

A microfluidic device was manufactured in the same manner as in Example 1, except that a voltage of 11 kV was applied to the dust collection plate when manufacturing the fiber, and the flow rate of the polymer solution was adjusted to 0.08 mL/min.

Experimental Example 1: Measurement of diameter of electrospun fiber

In the microfluidic device manufacturing process through Examples 1 to 3, the electrospun fibers were photographed through a scanning electron microscope (SEM) (HITACHI S-4800), and then measured using measurement software (ImageJ® software (National Institutes of Health, Bethesda, USA)) was used to measure the diameter of the electrospun fiber and is shown in Table 1 below.

Concentration of polymer solution (%) Flow rate of polymer solution (mL/min) Voltage of dust collection plate (kV) Diameter of electrospun fiber (μm) Example 1 17.5 0.10 9 12 Example 2 15.0 0.10 7 9 Example 3 15.0 0.08 11 6

In Examples 1 to 3, a fiber-shaped microfluidic channel was formed using electrospun fibers as a template, and in Table 1, the diameter of the electrospun fiber was the same as the diameter of the fiber-type microfluidic channel.

Through the results in Table 1 above, by controlling the flow rate (mL/min) of the polymer solution and the voltage (kV) applied on the dust collection plate when spinning through a syringe pump during electrospinning to produce fibers, the electrospun fibers It was confirmed that fibrous microfluidic channels with various diameters could be manufactured using the sieve as a template.

Experimental Example 2: Confirmation of formation of fibrous microfluidic channel

In order to confirm the microfluidic channel formed using the electrospun fiber contained in the second layer of the microfluidic device manufactured in Example 1 as a template, the second layer was dissolved in dichloromethane (DCM), an organic solvent. After immersion and drying, it was confirmed that a fibrous microfluidic channel was formed as a result of observation as shown in Figure 2.

In addition, as shown in FIG. 3, an aqueous solution containing a fluorescent substance was injected into the fibrous microfluidic channel and photographed with a confocal microscope, confirming that a fibrous microfluidic channel was formed.

Experimental Example 3: Formation of emulsion particles through fibrous microfluidic channels

When producing emulsion particles through the microfluidic device manufactured in Examples 1 to 3, the size of the emulsion particles formed was measured while controlling the flow rate of the oily substance.

Specifically, as the oily substance, an oily solution prepared by dissolving 2% concentration of Span 80 (Sigma-Aldrich, S6760-1L) in mineral oil (Sigma-Aldrich, 330760-1L) was used, and as the aqueous substance, used an aqueous solution prepared by dissolving 0.01% concentration of methylene blue hydrate (Sigma-Aldrich, 66720-100G) in distilled water.

In order to inject the oily material and the aqueous material into each inlet of the microfluidic device manufactured through Examples 1 to 3, an 18 gauge needle and a tygon tube (outer diameter: 2.38mm, inner diameter: 0.79mm) were attached to the syringe. ) and tubing connector (outer diameter: 1.58mm) were connected. In addition, the first inlet, second inlet, and outlet of the first layer were pierced with a 17 gauge needle and connected to a tubing connector to enable injection and discharge of each material.

Using a syringe pump, the oily material in the continuous phase was injected into the first injection port while adjusting as shown in Table 2 below, and the aqueous material in the discontinuous phase was injected into the second injection port at 0.3 μL/min. The oil-phase material and the aqueous-phase material met through the fiber-type microfluidic channel of the microfluidic device to form emulsion particles, which were obtained through the outlet of the microfluidic device.

The average diameter distribution of the particles was measured using a nano particle size analysis device (Dynamic light scattering method) (Zetasizer nano ZS, Malvern Instruments, Malvern, UK) for the emulsion particles manufactured with the microfluidic device prepared in Examples 1 to 3. The particle size at the accumulated 50% point was measured and shown in Table 2 and Figures 5 to 7 below.

Flow rate (μL/min) Emulsion particle size (μm) Example 1
(Channel diameter 12μm) 2.0 2.84 ±　0.75 3.0 1.85 ±0.53 4.0 1.29 ±　0.32 Example 2
(Channel diameter 9μm) 2.0 0.67 ±　0.17 3.0 0.43 ±　0.11 4.0 0.26 ±　0.06 Example 3
(Channel diameter 6μm) 2.0 0.13 ± 0.02 3.0 0.10 ± 0.01 4.0 0.08 ± 0.01

Through the results of Table 2 and Figures 5 to 7, by controlling the flow rate through a syringe pump in the embodiments in which the diameter of the fibrous microfluidic channel formed using the electrospun fiber body as a template is varied, various It was confirmed that an emulsion of particle size could be created.

In addition, through the results of FIG. 4, it was confirmed that not only were emulsions of various particle sizes produced, but as the flow rate of the oily material injected into the microfluidic device increased, the size of the emulsion particles became smaller, but the amount of particles produced increased.

All simple modifications or changes of the present invention fall within the scope of the present invention, and the specific scope of protection of the present invention will be made clear by the appended claims.

100: first floor
111: first inlet
112: 1st Euro
121: second inlet
122: 2nd Euro
131: outlet
132: 3rd Euro
140: Junction area
200: 2nd floor
210: Fibrous microfluidic channel formed using electrospun fiber as a template
300: Third layer

Claims (12)

It is a structure in which the first, second, and third layers are stacked in the order of top and bottom,
The first layer includes a first injection port through which an oily material is injected; a second injection port through which an aqueous substance is injected; And an outlet for discharging microdroplets,
The second layer includes fibrous microfluidic channels,
The third layer is a layer that supports the second layer,
The fibrous microfluidic channel is a microfluidic device in which the oil phase material and the water phase material flow to form micro droplets.
According to claim 1,
A microfluidic device, wherein the fibrous microfluidic channel includes one selected from the group consisting of microfiber-type channels, nanofiber-type channels, and combinations thereof.
According to claim 1,
The first layer includes a first flow path through which oily substances move; And a second flow path through which the aqueous material moves,
A microfluidic device wherein each discharge portion of the first flow path and the second flow path is located in a junction area where an oily substance and an aqueous substance meet.
According to claim 1,
The first layer further includes a third flow path connected to an outlet for movement of fine droplets,
A microfluidic device wherein the inlet of the third flow path is located corresponding to the position of the microfluidic channel of the second layer.
According to claim 3,
The second layer is a microfluidic device comprising a fibrous microfluidic channel at a position corresponding to a junction area of the first layer where the oil-phase material and aqueous-phase material moving through the first flow path and the second flow path meet.
According to claim 1,
The third layer includes a polydimethylsiloxane layer.
According to claim 1,
A microfluidic device, wherein the fibrous microfluidic channel has a diameter of 20 μm or less.
(1) producing a fiber body by electrospinning a polymer solution;
(2) manufacturing a second layer including a fibrous microfluidic channel using the electrospun fiber body;
(3) a first injection port through which an oily substance is injected using 3D printing; a second injection port through which an aqueous substance is injected; and an outlet for discharging fine droplets formed when the oily material and the aqueous material meet; manufacturing a first layer including a; and
(4) bonding the first layer to the top of the second layer and bonding the third layer supporting the second layer to the bottom.
According to claim 8,
Step (1) includes electrospinning the polymer solution at a flow rate of 0.01 to 0.50 mL/min and a voltage of 5 to 30 kV.
According to claim 8,
Step (2) is a step of impregnating the electrospun fiber in a solution containing polydimethylsiloxane, curing the polydimethylsiloxane, and dissolving the fiber in an organic solvent to form a fibrous microfluidic channel. Method for manufacturing a microfluidic device, including.
delete A method for producing microdroplets, comprising the step of generating microdroplets by injecting an oily substance and an aqueous substance into the microfluidic device of any one of claims 1 to 7.