KR101879657B1 - Apparatus for manufacturing a hydrogel and manufacturing method thereof - Google Patents

Apparatus for manufacturing a hydrogel and manufacturing method thereof Download PDF

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KR101879657B1
KR101879657B1 KR1020160022718A KR20160022718A KR101879657B1 KR 101879657 B1 KR101879657 B1 KR 101879657B1 KR 1020160022718 A KR1020160022718 A KR 1020160022718A KR 20160022718 A KR20160022718 A KR 20160022718A KR 101879657 B1 KR101879657 B1 KR 101879657B1
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hydrogel
manufacturing
wall structure
receiving
chamber
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KR1020160022718A
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Korean (ko)
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KR20170100307A (en
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이형석
강병준
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연세대학교 산학협력단
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Priority to KR1020160022718A priority Critical patent/KR101879657B1/en
Priority to US15/441,880 priority patent/US10737409B2/en
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/08—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor
    • B01J19/10—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor employing sonic or ultrasonic vibrations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061—Use of materials characterised by their function or physical properties
    • A61L26/008—Hydrogels or hydrocolloids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/52—Hydrogels or hydrocolloids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D39/00—Filtering material for liquid or gaseous fluids
    • B01D39/14—Other self-supporting filtering material ; Other filtering material
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
    • C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
    • C08J3/075—Macromolecular gels

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  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Health & Medical Sciences (AREA)
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Abstract

The present invention relates to an apparatus for manufacturing a hydrogel, comprising: a hydrogel receiving means for receiving a hydrogel having fluidity before gelation; and a stimulation means for applying a magnetic field to the hydrogel to generate a flow in the hydrogel, The gel receiving means includes a chamber which is a space for accommodating the hydrogel and a wall structure surrounding the chamber, and the wall structure includes a passage region through which the magnetic pole generated by the magnetic pole means passes, And a shielding region for shielding the shielding portion.

Description

TECHNICAL FIELD [0001] The present invention relates to a hydrogel manufacturing apparatus and a hydrogel manufacturing method using the hydrogel manufacturing apparatus,

The present invention relates to an apparatus and a method for manufacturing a hydrogel, and more particularly, to a device and a method for producing a hydrogel having an anisotropic mechanical strength in a hydrogel by having a stiffness different from one another according to regions. And a method for producing a hydrogel using the apparatus.

A hydrogel refers to a porous material made of a water-soluble polymer material. The porous material is a material having a pore structure therein. The porous material may have mechanical strength, permeability, electroconductivity, and the like depending on factors such as porosity, pore size, distribution, Properties have characteristics that change. These characteristics are applied to various applications such as filters, electrodes, gas sensors, gas seperators, scaffolds for wet tissue implantation, wet dressings, and mask pack materials have.

Hydrogels are a type of polymer that combine with monomers and cross-linkers to form a pore structure that can hold water inside. Such hydrogels are excellent in hyrophilicity and biocompatibility, and therefore, many studies for medical applications are being conducted. Hydrogels, for example, contain water in them to provide a favorable environment for cells and drugs, are suitable for transporting the nutrients necessary for cell culture, and are easily transformed by cell adhesion ligands. And is not biocompatible. Therefore, it is used as a material for tissue engineering scaffold, drug delivery system, patch for wound healing, etc. Recently, a structure of soft robotics And microfluidic actuators have been actively studied.

However, hydrogels have a disadvantage in that their mechanical strength is weak in actual applications, which limits application. Therefore, many researches have been carried out to improve the mechanical properties by applying specific stimuli to the hydrogel. In particular, hydrogels are used for culturing stem cells. It is known that hydrogel stiffness affects the differentiation of stem cells. That is, even if the same stem cells are differentiated, stem cells are differentiated depending on the rigidity of the hydrogel in which the stem cells are cultured (see FIG. 1). Therefore, adjusting the mechanical strength of the hydrogel is a very important factor in determining the application range of the hydrogel.

As a first attempt to control the mechanical properties of a hydrogel, there is a method of improving the ductility and toughness in a specific direction by using a double-network hydrogel. In the course of manufacturing, various complicated steps are required, There are restrictions on the materials available for forming the mesh. Another method is the directional freeze-thaw method, which has limited formation temperature and is not suitable for application to biomaterials due to the high possibility of damage to the material during the freeze-thaw process. In recent years, studies have been made to control the mechanical properties of hydrogels by adding ultrasonic waves to the hydrogels (see FIG. 2). However, this also does not provide a means for controlling the stiffness of the hydrogels within the hydrogels, Is not appropriate.

U.S. Published Patent Application No. 2015/0165091 (Jun. U.S. Published Patent Application No. 2012/0070427 (March 22, 2012)

The present invention has been made to solve the above problems of the prior art and it is an object of the present invention to provide a device capable of adjusting the stiffness in the hydrogel by applying a flow to the hydrogel and further controlling the stiffness in each region in the hydrogel, And a method thereof.

The present invention relates to an apparatus for producing a hydrogel, comprising: a hydrogel receiving means for receiving a hydrogel having fluidity before gelation; and a stimulating means for generating a flow in the hydrogel by applying a stimulus to the hydrogel, And the gel is formed to have a different stiffness according to the flow by the stimulating means. Further, the hydrogel receiving means includes a chamber, which is a space for receiving the hydrogel, and a wall structure surrounding the chamber, wherein the wall structure has a passage region for passing a magnetic pole generated by the magnetic pole means, And a blocking region for blocking the generated stimulus.

In one embodiment of the present invention, the stimulus may be a surface acoustic wave generating means or an ultrasonic transducer. Preferably, the surface acoustic wave generating means may include a substrate and an IDT electrode formed on the substrate. have.

Further, in one embodiment of the present invention, the wall structure is formed of PDMS, and the thickness of the wall structure in the passageway region is formed to be relatively smaller than the thickness of the wall structure in the blocking region. And preferably, in one embodiment of the present invention, the hydrogel receiving means is attached to the substrate.

The present invention provides a method for manufacturing a hydrogel using the above-described hydrogel manufacturing apparatus, comprising: receiving a hydrogel having fluidity before being gelated in the hydrogel receiving means; And controlling the stiffness of the hydrogel by applying a surface acoustic wave stimulus to the hydrogel. In addition, the method of manufacturing a hydrogel according to the present invention comprises the steps of: setting a thickness of a wall structure of the hydrogel receiving structure so that a passage region through which a stimulus passes and a blocking region where a stimulus is blocked; Injecting a hydrogel into the chamber of the hydrogel receiving structure; And applying a stimulus to the hydrogel through the stimulating means. Preferably, after the step of injecting the hydrogel into the chamber, the step of covering the chamber with the cover may be further included.

The stiffness can be controlled by changing the internal structure of the hydrogel using a means such as a surface acoustic wave. Further, by forming a flow selectively in the hydrogel, an anisotropic hydrogel can be prepared by controlling the hydrogel to have different stiffness depending on the region. Since the present invention utilizes the flow generated in the hydrogel, it is possible to overcome the limitation of the application of the material, which is a disadvantage of the conventional method of changing the internal structure of the hydrogel.

Figure 1 shows the effect of hydrogel stiffness on differentiation of stem cells.
Fig. 2 shows a technique of changing the stiffness of the hydrogel by ultrasonic waves according to the prior art.
Figure 3 shows a hydrogel.
4 is a top view of an apparatus according to an embodiment of the present invention.
5 is a front view of an apparatus according to an embodiment of the present invention.
6 is a perspective view showing a wall structure of the present invention.
7 illustrates an IDT electrode according to an embodiment of the present invention
8 is a conceptual diagram illustrating a process in which a surface acoustic wave generated from an IDT electrode is transferred to a hydrogel in an apparatus according to an embodiment of the present invention.
FIG. 9 is a flowchart showing a method of manufacturing a hydrogel.
10 is a photograph showing the flow state in the hydrogel according to time.
11 is a graph showing the velocity of the flow according to the voltage magnitude of the AC power applied to the IDT electrode.

FIG. 3 illustrates a basic principle of a hydrogel stiffness control technique according to an embodiment of the present invention. When the hydrogel is flowed into the hydrogel solution during the gelation, it has an anisotropic structure due to flow direction and flow rate.

 As shown in FIG. 3 (a), when a portion of the hydrogel is stimulated, a flow is generated inside the hydrogel, which changes the internal structure of the hydrogel. In the embodiment according to FIG. 3 (a), when a stimulus is applied to the central portion of the hydrogel, a first flow occurs in a direction in which the stimulus is received, and this flow generates a circulating flow inside the hydrogel.

As a result, it was confirmed that the higher the flow velocity, the lower the stiffness of the hydrogel. That is, controlling the position and shape of the stimulus applied to the hydrogel can control the flow inside the hydrogel, and controlling the flow can partially control the stiffness of the hydrogel.

As shown in FIG. 3 (a), when the magnetic pole is applied to the center portion of the hydrogel, the flow velocity in the central portion of the hydrogel is formed at the fastest speed. As shown in FIGS. 3 (b) and 3 The central portion of the gel had a relatively low stiffness and thus had a soft property, and the side portion of the hydrogel was relatively hard to obtain a hydrogel having hard properties.

In order to generate the flow in the hydrogel, an external stimulus must be applied. The external stimulus can be obtained through a surface acoustic wave or an ultrasonic transducer. In order to precisely control the stiffness of the hydrogel, Acoustic Wave (SAW) is the most suitable method, and the following description will focus on a method using a surface acoustic wave.

FIG. 4 is a plan view of a hydrogel manufacturing apparatus 100 according to an embodiment of the present invention, FIG. 5 is a front view, and FIG. 6 is a side view. The apparatus 100 for manufacturing a hydrogel according to an embodiment of the present invention includes a substrate 110, a hydrogel receiving structure 200 formed on the substrate 110, a hydrogel receiving structure 200, A lid 300 for sealing and sealing, and an IDT electrode 120 as a surface acoustic wave generating means.

The substrate 110 can be mainly made of lithium niobate (LiNbO 3 ), quartz (Quartz), or lithium tantalite (LiTaO 3 ), but the material is not particularly limited if it is a material capable of generating surface acoustic waves.

A hydrogel receiving structure 200 capable of receiving a hydrogel is formed on a substrate 110. The hydrogel receiving structure includes a chamber 210 for providing a space for accommodating a hydrogel, And a wall structure 220. The wall structure 220 surrounds the chamber 210. The wall structure 220 formed on the wall structure 220 in the direction of the IDT electrode 120 has a passage region 221 having a relatively small thickness, And includes a relatively large blocking region 222.

The wall structure 220 is mainly made of PDMS (Polydimethylsiloxane). However, the material of the fluid receiving channel 150 may be any material capable of storing the fluid therein, and the material of the wall structure 220 is not particularly limited.

The thickness of the wall structure formed between the hydrogel and the IDT electrode 120 accommodated in the chamber 210 greatly affects the degree of transmission of the surface acoustic waves generated by the IDT electrode 120 to the hydrogel. 4 and 6, the center portion of the chamber 210 is relatively narrow in the passage region 221 having a relatively small wall structure thickness, and both ends of the chamber 210 are relatively It can be seen that the structure is placed in the blocking region 222 having a large thickness. In this state, when the surface acoustic wave is generated in the IDT electrode 120, most of the surface acoustic waves propagating to the channel region 221 are transmitted to the hydrogel contained in the chamber 210, while the surface acoustic wave propagating to the blocking region 222 Most of the energy is absorbed by the wall structure and most of the surface acoustic waves are not transmitted to the hydrogel accommodated in the chamber 210. This transmission mechanism of surface acoustic waves is illustrated in FIG.

4 to 6, the size and shape of the passage area 221 and the blocking area 222 are determined in order to generate a flow in the central portion of the hydrogel received in the chamber 210, It will be understood by those skilled in the art that the position and the ratio of the formation of the passage region 221 and the blocking region 222 can be adjusted in order to adjust the region to which the stimulation is applied. That is, according to the present invention, the flow pattern in the hydrogel can be freely adjusted according to the arrangement manner of the wall structure.

As described above, the surface acoustic wave is generated by the IDT electrode 120. The IDT electrode 120 is formed by attaching a piezoelectric material to a substrate. When AC power is applied to the IDT electrode 120, a surface acoustic wave is generated on the substrate 110.

7, the basic structure of the IDT electrode 120 is shown. The upper electrode 121 and the lower electrode 122 each include a plurality of branches, and the branches are arranged in a staggered manner. It is possible to adjust the wavelength or frequency of the surface acoustic wave generated by adjusting the widths of the electrode branches and the interval between the adjacent electrode branches (the width of the electrode branches and the interval between the electrode branches and the branches are determined to be 1/4 of the wavelengths) (? / 4)).

Referring to FIG. 9, a method of manufacturing the hydrogel according to the present invention will be described below. First, the thickness of the wall structure of the hydrogel receiving structure should be adjusted (S600). This is a process of determining the position and the ratio of the passage region 221 and the blocking region 222, ≪ / RTI >

After the structure of the hydrogel receiving structure is determined, the hydrogel receiving structure 200 is attached to the substrate 110 (S200), and the hydrogel material is injected into the chamber 210 of the hydrogel receiving structure 200 (S300), the lid 300 is attached so that the chamber 210 can be sealed (S400).

When an AC power source is applied to the IDT electrode 120 (S500), a surface acoustic wave is generated through the substrate 110. The surface acoustic waves are transmitted to the hydrogel, mechanically stimulating the hydrogel to generate an internal flow (S600), and when the flow of the hydrogel continues for a certain period of time, an anisotropic hydrogel having a partially changed stiffness is formed depending on the degree of flow (S700).

FIG. 10 is a photograph showing a surface acoustic wave applied to a hydrogel using an apparatus according to the above-described embodiment of the present invention, and FIG. 11 is a graph showing a flow rate of a flow according to a voltage of an applied AC power source. In FIGS. 10 and 11, the circles represent areas where the main flow is directly affected by the surface acoustic waves, while the areas indicated by the reverse osmosis are areas that are not directly affected by the surface acoustic waves. flow) is generated.

In FIG. 10, the portion indicated with a relatively dark area is a region in which flow occurs. In the early stage, only the main flow exists. However, it can be seen that the return flow is formed with time. Referring to FIG. 11, it can be seen that the higher the voltage of the AC power applied to the IDT electrode 120, the faster the flow speed.

As the material of the hydrogel used in the present invention, various synthetic polymer materials and natural polymer materials can be used. Representative synthetic polymer materials include polyacrylamide (PAAM), hyaluronic acid (HA), or hyaluronic acid (PAC), polyvinyl alcohol, polyethylene oxide and the like, and natural polymeric materials such as collagen and polysaccharides (for example, chitosan (polyvinyl alcohol), polyvinylacetate Chitosan, alginate, agarose) and the like can be used.

100: Hydrogel manufacturing apparatus 110: substrate
120: IDT electrode 200: Hydrogel receiving structure
210: chamber 220: wall structure
221: passage area 222: blocking area
300: cover

Claims (10)

The present invention relates to a hydrogel manufacturing apparatus,
A hydrogel receiving means for receiving a hydrogel having fluidity before gelation; And
And stimulating means for applying a stimulus to the hydrogel to generate a flow in the hydrogel,
Wherein the hydrogel is formed to have a different stiffness according to the flow of the stimulating means.
[2] The apparatus of claim 1, wherein the hydrogel receiving means comprises a chamber which is a space for accommodating the hydrogel and a wall structure surrounding the chamber, wherein the wall structure comprises: And a blocking region for blocking the stimulation generated by the stimulation means.
The apparatus for manufacturing a hydrogel according to claim 1 or 2, wherein the stimulating means is a surface acoustic wave generating means or an ultrasonic transducer.
4. The apparatus for manufacturing a hydrogel according to claim 3, wherein the stimulating means is surface acoustic wave generating means including a substrate and an IDT electrode formed on the substrate.
The apparatus for manufacturing a hydrogel according to claim 2, wherein the thickness of the wall structure in the passage region is relatively smaller than the thickness of the wall structure in the blocking region.
[6] The apparatus for manufacturing a hydrogel according to claim 4, wherein the hydrogel receiving means is attached to the substrate.
The apparatus for manufacturing a hydrogel according to claim 1, wherein the wall structure of the hydrogel receiving means is formed of PDMS.
A hydrogel manufacturing method using the hydrogel manufacturing apparatus according to claim 1,
Receiving a hydrogel having fluidity before being gelated in the hydrogel receiving means; And
And adjusting the stiffness of the hydrogel by applying a surface acoustic wave stimulus to the hydrogel to change an internal structure of the hydrogel.
A hydrogel manufacturing method using the hydrogel manufacturing apparatus according to claim 2,
Setting a thickness of a wall structure of the hydrogel receiving structure so as to set a passage region through which the magnetic pole is passed and a blocking region where the magnetic pole is blocked;
Injecting a hydrogel into the chamber of the hydrogel receiving structure; And
And applying a stimulus to the hydrogel through the stimulating means.
[12] The method of claim 9, further comprising the step of covering the chamber with a lid after the step of injecting the hydrogel into the chamber.


KR1020160022718A 2016-02-25 2016-02-25 Apparatus for manufacturing a hydrogel and manufacturing method thereof KR101879657B1 (en)

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US15/441,880 US10737409B2 (en) 2016-02-25 2017-02-24 Apparatus and method of controlling stiffness of soft material

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100700324B1 (en) * 2005-11-07 2007-03-29 주식회사 웰스킨 Culture method for matrix comprising collagen improving porous and tensile strength by stimulation-system
JP2011080930A (en) * 2009-10-09 2011-04-21 Toppan Printing Co Ltd Method for manufacturing electrophoretic gel cassette, and electrophoretic gel filling method
KR101053219B1 (en) * 2002-12-10 2011-08-02 소니 가부시키가이샤 Polymer Actuator
JP2012130920A (en) * 2006-05-02 2012-07-12 Monash Univ Concentration and dispersion of small particles in small volume of fluid caused by using acoustic energy
JP5464105B2 (en) * 2010-09-06 2014-04-09 セイコーエプソン株式会社 Gel manufacturing apparatus and gel

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120070427A1 (en) 2009-06-01 2012-03-22 Trustees Of Tufts College Vortex-induced silk fibroin gelation for encapsulation and delivery
US20150165091A1 (en) 2012-03-30 2015-06-18 University Of Rochester Controlling extracellular matrix protein microstructure with ultrasound

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101053219B1 (en) * 2002-12-10 2011-08-02 소니 가부시키가이샤 Polymer Actuator
KR100700324B1 (en) * 2005-11-07 2007-03-29 주식회사 웰스킨 Culture method for matrix comprising collagen improving porous and tensile strength by stimulation-system
JP2012130920A (en) * 2006-05-02 2012-07-12 Monash Univ Concentration and dispersion of small particles in small volume of fluid caused by using acoustic energy
JP2011080930A (en) * 2009-10-09 2011-04-21 Toppan Printing Co Ltd Method for manufacturing electrophoretic gel cassette, and electrophoretic gel filling method
JP5464105B2 (en) * 2010-09-06 2014-04-09 セイコーエプソン株式会社 Gel manufacturing apparatus and gel

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