미세유체 장치에서 부분젤화법을 이용한 단분산성 펙틴 하이드로젤 미세섬유의 제조

진시형,김채연,이병진,심규락,김동영,이창수 한국청정기술학회 2017 청정기술 Vol.24 No.3

This study introduces a method to easily fabricate highly monodisperse pectin hydrogel microfibers in a microfluidic device by using partial gelation. The hydrodynamic parameters between the pectin aqueous solution and the calcium ions containing oil solution are precisely controlled to form a stable elongation flow of the pectin aqueous solution, and partial gelation of the pectin aqueous solution is performed by the chelating of the calcium ions at the interface between the two phases. The partially gelled pectin aqueous solution is phase-separated from the oil solution in an aqueous calcium chloride solution outside the microfluidic device and is completely gelled to produce monodisperse pectin hydrogel microfibers. The thickness of the pectin hydrogel microfiber is controlled in a reproducible manner by controlling the volumetric flow rate of the initially injected pectin aqueous solution. The pectin hydrogel microfibers were 200 to 500 micrometers in diameter and had a coefficient of variation below 5% under all thickness conditions, indicating that the pectin hydrogel microfibers produced by partial gelation are highly monodisperse. In addition, biomaterials can be immobilized to the pectin hydrogel microfibers produced by a single process, demonstrating the possibility that our pectin hydrogel microfiber can be used as carriers for biomaterials or tissue engineering. 본 연구는 미세유체 장치에서 매우 균일한 펙틴 하이드로젤 미세섬유를 부분젤화법을 통해 손쉽게 제조하는 방법을 소개한다. 펙틴 수용액과 이와 섞이지 않는 칼슘이 분산된 오일용액 사이의 수력학적 변수들을 조절하여 펙틴 수용액의 흐름을 안정적으로 늘어진 유동을 형성하고 두 상의 계면에서 칼슘 이온의 킬레이트화 반응으로 펙틴 수용액을 부분젤화 시킨다. 부분젤화된 펙틴 수용액은 미세유체 장치 외부의 염화칼슘 수용액에서 오일 용액과 상분리 되고 완전히 젤화되어 미세섬유로제조된다. 펙틴 하이드로젤 미세섬유의 굵기는 초기 주입되는 펙틴 수용액의 부피유속을 조절함으로써 재현성 있게 제어된다. 제조된 펙틴 하이드로젤 미세섬유의 직경은 200에서 500 마이크로미터 범위이며 모든 두께 조건에서 5% 이하의 변동계수를 가짐으로써 매우 균일함을 증명하였다. 또한 펙틴 하이드로젤 미세섬유에 생체물질을 단일공정으로 고정화 함으로써생체물질 담지체나 조직공학의 지지체로써 사용될 수 있는 가능성을 보여준다.

미세유체 장치에서 부분젤화법을 이용한 단분산성 펙틴 하이드로젤 미세섬유의 제조

진시형(Si Hyung Jin),김채연(Chaeyeon Kim),이병진(Byungjin Lee),심규락(Kyu-Rak Shim),김동영(Dong Young Kim),이창수(Chang-Soo Lee) 한국청정기술학회 2017 청정기술 Vol.23 No.3

본 연구는 미세유체 장치에서 매우 균일한 펙틴 하이드로젤 미세섬유를 부분젤화법을 통해 손쉽게 제조하는 방법을 소개한다. 펙틴 수용액과 이와 섞이지 않는 칼슘이 분산된 오일용액 사이의 수력학적 변수들을 조절하여 펙틴 수용액의 흐름을 안정적으로 늘어진 유동을 형성하고 두 상의 계면에서 칼슘 이온의 킬레이트화 반응으로 펙틴 수용액을 부분젤화 시킨다. 부분젤화된 펙틴 수용액은 미세유체 장치 외부의 염화칼슘 수용액에서 오일 용액과 상분리 되고 완전히 젤화되어 미세섬유로 제조된다. 펙틴 하이드로젤 미세섬유의 굵기는 초기 주입되는 펙틴 수용액의 부피유속을 조절함으로써 재현성 있게 제어된다. 제조된 펙틴 하이드로젤 미세섬유의 직경은 200에서 500 마이크로미터 범위이며 모든 두께 조건에서 5% 이하의 변동계수를 가짐으로써 매우 균일함을 증명하였다. 또한 펙틴 하이드로젤 미세섬유에 생체물질을 단일공정으로 고정화 함으로써 생체물질 담지체나 조직공학의 지지체로써 사용될 수 있는 가능성을 보여준다. This study introduces a method to easily fabricate highly monodisperse pectin hydrogel microfibers in a microfluidic device by using partial gelation. The hydrodynamic parameters between the pectin aqueous solution and the calcium ions containing oil solution are precisely controlled to form a stable elongation flow of the pectin aqueous solution, and partial gelation of the pectin aqueous solution is performed by the chelating of the calcium ions at the interface between the two phases. The partially gelled pectin aqueous solution is phase-separated from the oil solution in an aqueous calcium chloride solution outside the microfluidic device and is completely gelled to produce monodisperse pectin hydrogel microfibers. The thickness of the pectin hydrogel microfiber is controlled in a reproducible manner by controlling the volumetric flow rate of the initially injected pectin aqueous solution. The pectin hydrogel microfibers were 200 to 500 micrometers in diameter and had a coefficient of variation below 5% under all thickness conditions, indicating that the pectin hydrogel microfibers produced by partial gelation are highly monodisperse. In addition, biomaterials can be immobilized to the pectin hydrogel microfibers produced by a single process, demonstrating the possibility that our pectin hydrogel microfiber can be used as carriers for biomaterials or tissue engineering.

Generation and characterization of monodisperse gelatin hydrogel microbeads in a microfluidic system

박기수,김채연,남진오,강성민,이창수 한국공업화학회 2016 한국공업화학회 연구논문 초록집 Vol.2016 No.0

We present a novel method for the synthesis of monodisperse gelatin microbeads in a microfluidic system. Aqueous gelatin droplets were continuously produced in an immiscible continuous oil fluid. By cooling the droplets, the aqueous gelatin droplets solidified into hydrogel microbeads. The produced gelatin microbeads have a high monodispersity and fast response to environmental temperature. In addition, the size of the prepared microbeads can be manipulated by altering the flow rate of the continuous phase or aqueous phase, and the physical strength of the gelatin microbeads can be controlled by simply changing the gelatin concentration. Furthermore, this approach enables the preparation of monodisperse microbeads with the ability to exhibit different thermosensitivities and encapsulate colloidal particles under mild conditions, which demonstrate sequential release of the desired encapsulants according to the responsive temperature.

콜로이드 응집법에 의한 구형 실리카 분체 제조시 입자 크기 제어에 관한 연구

이상우 ( Lee Sang U ),이창일 ( Lee Chang Il ),이융 ( Lee Yung ),함영민 ( Ham Yeong Min ) 한국공업화학회 2003 공업화학 Vol.14 No.7

Colloidal silica를 urea 및 formaldehyde의 중합공정을 통하여 얻어지는 urea-formaldehyde resin과 함께 응집시킨 후 유기물의 제거과정을 통하여 구형 실리카 분체를 제조하였다. 구형 실리카 분체 제조시 colloidal silica 및 formaldehyde의 농도와 반응물의 pH, 산의 종류, 용매의 부피 및 혼합용매의 종류를 변화시켜 입자크기에 대한 영향을 조사하였다. 열중량 분석 및 FT-IR 분석을 통하여 응집체 중의 유기물의 열분해 거동 및 순수 실리카의 특성 피크를 확인하고, SEM분석을 통해 입자의 형상 및 크기를 측정하여 평균입경과 균일도(monodispersity)를 분석하였으며, BET법을 이용하여 실리카 입자의 비표면적, 기공크기 및 기공분포를 측정하였다. 실험결과, colloidal silica의 농도가 높아질수록 입자 크기가 증가하는 경향을 관찰하였으며, formaldehyde의 농도를 변화시켰을 경우 urea와 formaldehyde의 몰비가 1:1~1:1.2일 경우 가장 단분산된 실리카 분체를 제조할 수 있었다. 또한, pH가 낮아질수록 입자크기가 작아지고 입도분포의 균일도가 증가되는 경향을 나타내었다. Spherical silica powder was fabricated by using colloid aggregation method which involves polymerization of urea with formaldehyde. This aggregation process includes formation of urea-formaldehyde resin (UF resin) and growth of silica-UF resin aggregates. After the aggregation process, the UF resin could be burned off to form a pure spherical silica powder The effect of concentration of colloidal silica and formaldehyde. pH of reactants, type of acid catalysts, and solvents on particle size of spherical silica powder was investigated. The TGA traces and FT-IR spectra were collected to examine decomposition temperature of UF resin and the bond structure of silica Particle shape, size, and monodispersity was analyzed by SEM. Specific surface area, pore diameter and pore distribution were calculated from N₂ Adsorption using BET method. It was found that increase in the concentration of colloidal silica increased average particle size of silica powder. Optimum molar ratio of urea(fixed condition) and formaldehyde for preparing monodispersed silica powder was 1:1-1:1.2. In addition decrease in pH decreased average particle size of silica powder and increased monodispersity of silica powder.

Effects of Type and Content of Co-Surfactants on the Preparation of Spherical and Monodisperse Alumina Powder under W/O Emulsion Method using Paraffin Oil

Lee, Yoong,Hahm, Yeong Min 한국공업화학회 2003 Journal of Industrial and Engineering Chemistry Vol.9 No.6

Spherical and monodisperse alumina powder was fabricated hy controlling the type, content and composition of emulsifiers under W/O emulsion method including combustion process. Aq. Al₂O₃ sol of pH =3 obtained from AI(N0₃)₃. 9H₂0 was used as water phase [W] and paraffin oil containing emulsifiers was used as oil phase [O]. Span80 (sp80) was used as a single-surfactant, [sp8O & tween8O(tw8O)] as mixed-surfactant, and n-butanol, n-octanol as well as n-dodecanol were used as co-surfactants. As results, under 2000rpm, average particle size of spherical alumina fabricated by adding 0.4 vol% n-butanol in emulsion containing [sp8O & tw80] of HLB, = S became smaller than that obtained from the only usage of [sp80 & tw8O] of HLB, = ? regardless of 0:W volumetric ratio and vol% emulsifiers. Under 4000 rpm and 0:W = 8:1.5, the aggregation and coalescence among particles fabricated by the usage of 2.5 vol% [sp80 & tw8O] of HLB,, = S were lower than those among particles prepared by the usage of 2.5 vol% sp80. Moreover, the lowest value of monodispersity, 1.03, in this study could be gained by the usage of 0.25 vol% n-butanol together with 2.5 vol% [sp80 & tw8O] of HLB,= S?.

미세 채널에서 칼슘이온 물질전달을 이용한 단분산성 알지네이트 하이드로젤입자의 실시간 젤화

송영신 ( Young Shin Song ),이창수 ( Chang Soo Lee ) 한국화학공학회 2014 Korean Chemical Engineering Research(HWAHAK KONGHA Vol.52 No.5

본 논문은 가교제의 물질전달을 통한 실시간 생체고분자의 젤화 과정으로 단분산성을 갖는 구형의 알지네이트 하이드로젤을 미세유체 채널 내에서 제조하는 방법에 관한 연구이다. 먼저 미세유체 채널 내에서 단분산성 알지네이트 액적들을 형성하고 연속상에 분산된 염화칼슘 분자들의 물질전달 과정을 통해 실시간 젤화과정이 이루어지게 하여 알지네이트 하이드로젤 입자를 제조하였다. 이때, 미세유체 채널에서 형성되는 액적의 크기는 손쉽게 케필러리 수(capillarynumber)와 분산상의 유속 조절을 통하여 제어할 수 있다. 본 방법은 미세유체 채널 내에서 안정적인 액적을 형성할 수있고 칼슘 가교제로 제조된 알지네이트 하이드로젤 입자들은 균일한 크기 분포를 가지며(C.V=2.71%) 유속, 점도, 및계면장력의 조절을 통하여 30 μm에서 60 μm까지의 다양한 크기의 알지네이트 하이드로젤 입자를 제조할 수 있다. 본논문에서 제시한 간단한 미세유체 접근방법을 통해 제조되는 단분산성을 갖는 알지네이트 하이드로젤 입자는 생체물질들을 손쉽게 함입(encapsulation)할 수 있으며 이는 식품, 화장품, 잉크 및 약물 등의 전달체로 활용이 가능하고 생체적합성이 뛰어나 세포이식 분야에도 활용될 가능성이 있다. A microfluidic method for the in situ production of monodispersed alginate hydrogels using biocompatiblepolymer gelation by crosslinker mass transfer is described. Gelation of the hydrogel was achieved in situ by the dispersedcalcium ion in the microfluidic device. The capillary number (Ca) and the flow rate of the disperse phase whichare important operating parameters mainly influenced the formation of three distinctive flow regions, such as dripping,jetting, and unstable dripping. Under the formation of dripping region, monodispersed alginate hydrogels having a narrowsize distribution (C.V=2.71%) were produced in the microfluidic device and the size of the hydrogels, ranging from30 to 60 μm, could be easily controlled by varying the flow rate, viscosity, and interfacial tension. This simple microfluidicmethod for the production of monodisperse alginate hydrogels shows strong potential for use in delivery systemsof foods, cosmetics, inks, and drugs, and spherical alginate hydrogels which have biocompatibility will be applied to celltransplantation.

Nanoparticle Arrays: Sub‐Nanometer Level Size Tuning of a Monodisperse Nanoparticle Array Via Block Copolymer Lithography (Adv. Funct. Mater. 2/2011)

Shin, Dong Ok,Lee, Duck Hyun,Moon, Hyoung‐,Seok,Jeong, Seong‐,Jun,Kim, Ju Young,Mun, Jeong Ho,Cho, Heesook,Park, Soojin,Kim, Sang Ouk WILEY‐VCH Verlag 2011 Advanced functional materials Vol.21 No.2

<P><B>Abstract</B></P><P>The fabrication and catalytic application of a size‐tunable monodisperse nanoparticle array enabled by block copolymer lithography is demonstrated. Highly uniform vertical cylinder nanodomains are achieved in poly(styrene‐<I>block</I>‐4‐vinylpyridine) (PS‐<I>b</I>‐P4VP) diblock copolymer thin‐films by solvent annealing. The prominent diffusion of the anionic metal complexes into the protonated P4VP cylinder nanodomains occurs through specific electrostatic interactions in a weakly acidic aqueous solution. This well‐defined diffusion with nanoscale confinement enables preparation of the laterally ordered monodisperse nanoparticle array with sub‐nanometer level precise size tuning. The controlled growth of monodisperse nanoparticle arrays is proven by their catalytic use for vertical carbon nanotube (CNT) growth via plasma enhanced chemical vapor deposition (PECVD). Since the size of the catalyst particles is the decisive parameter for the diameters and wall‐numbers of CNTs, the highly selective growth of double‐walled or triple‐walled CNTs could be accomplished using monodisperse nanoparticle arrays.</P>

화장품용 유화 제조기술 최근동향

황소라(Sora Hwang),남진오(Jin-Oh Nam),이병진(Byung-Jin Lee),송우호(Woo-Ho Song),이창수(Chang-Soo Lee) 한국생물공학회 2012 KSBB Journal Vol.27 No.4

Emulsions are mixture of immiscible liquids in which one is dispersed in all over the other. They have been applied to many applications including cosmetics, foods, drug delivery system (DDS), fine chemicals, and chemical separations. Especially, emulsion technology is one of the most useful technique to formulate cosmetics such as eye cream, foundation, and foam cleansing. In general, the emulsions can be generated by mechanical agitation of two immiscible fluids. However, the emulsions obtained by conventional method have limited in stability, monodispersity, and complicate process. We describe here preparation techniques of representative cosmetic emulsions such as liposome, liquid crystal emulsion, nanoemulsion, multiple emulsion, and pickering emulsion. Furthermore, various factors which can control the physical properties of each cosmetic emulsions are briefly discussed.

미세채널에서 수력학적 조절을 통한 단분산성 다중 액적 생성

강성민 ( Sung Min Kang ),최창현 ( Chang Hyung Choi ),황소라 ( So Ra Hwang ),정재민 ( Jae Min Jung ),이창수 ( Chang Soo Lee ) 한국화학공학회 2012 Korean Chemical Engineering Research(HWAHAK KONGHA Vol.50 No.4

This study reports the microfluidic preparation of monodisperse multiple emulsions using hydrodynamic control. To generate multiple emulsions, we fabricate a microfluidic capillary device based on co-flowing stream without any surface modification of microchannels. Based on the system, we can successfully generate multiple emulsions (W/O/W) using water containing 0.5 wt% Tween 20, n-hexadecane with 5 wt% Span 80, and 10 wt% poly (vinyl alcohol) (PVA) aqueous solution, respectively. Furthermore, we control the number of inner droplets by modulation of flow rate of inner fluid at fixed flow rate of middle and outer fluid. The multiple emulsions having precisely controlled inner droplets` size and number can be applicable for multiple chemical reactions as an isolated microreactor.

마이크로채널 내 이중유화 액적 형성을 통한 마이크로캡슐 제조

남진오 ( Jin Oh Nam ),최창형 ( Chang Hyung Choi ),김종민 ( Jong Min Kim ),강성민 ( Sung Min Kang ),이창수 ( Chang Soo Lee ) 한국화학공학회 2013 Korean Chemical Engineering Research(HWAHAK KONGHA Vol.51 No.5

본 연구는 액적기반 미세유체 장치를 이용하여 단분산성 마이크로캡슐의 간단한 제조방법에 관한 것이다. 본 연구에서 제시한 제조 방법은 이중액적을 생성시키기 위해 기존의 복잡한 표면처리가 필요한 이중 유화과정을 대신하여 하나의 교차점을 가진 단일공정을 사용하고자 한다. 먼저, 분산상은 광중합이 가능한 ethoxylated trimethylolpropane triacrylate (ETPTA) 단량체와 fluorocarbon (FC-77) 오일을 사용하고 연속상은 poly(vinyl alcohol) (PVA) 수용액을 사용하였으며, 미세유체 채널 내부로 흘려 주면 하나의 교차점에 흐름이 집중되어 균일한 이중액적을 생성한다. 생성된 이중액적은 광중합을 통해 마이크로캡슐을 제조한다. 상기 방법은 ETPTA 유체의 부피유속을 조절하여 이중액적의 껍질두께 제어가 가능하고 연속상인 물의 부피유속을 조절하여 전체 직경을 제어할 수 있다. 더 나아가, 본 시스템을 사용하여 다양한 물질들을 함입한 마이크로캡슐을 제작할 수 있으며, 약물전달시스템의 응용 기술에 활용될 것으로 예측된다. In this study, we present simple microfluidic approach for the synthesis of monodisperse microcapsules by using droplet-based system. We generate double emulsion through single step in the microfluidic device having single junction while conventional approaches are limited in surface treatment for the generation of double emulsion. First, we have injected disperse fluid containing FC-77 oil and photocurable ethoxylated trimethylolpropane triacrylate (ETPTA) and water containing 3 wt% poly(vinyl alcohol) (PVA) as continuous phase into microfluidic device. Under the condition, we easily generate double emulsion with high monodispersity by using flow focusing. The double emulsion droplets are transformed into microcapsules under the UV irradiation via photopolymerization. In addition, we control thickness of double emulsion`s shell by controlling flow rate of ETPTA. We also show that the size of double emulsions can be controlled by manipulation of flow rate of continuous phase. Furthermore, we synthesize microcapsules encapsulating various materials for the application of drug delivery systems.