Scale-Up of Monodisperse Emulsion/Bubble Generation using microfluidic device

정헌호 한국공업화학회 2019 한국공업화학회 연구논문 초록집 Vol.2019 No.0

Emulsion and gas bubble has led to significant progress in multiple area including materials synthesis, ultrasound imaging, and droplet-based high-throughput biological assay. One important challenge that may determine the commercial success and translation of microfluidic technologies is the mass production of monodisperse droplets and bubbles. In this work, we have developed a three-dimensional monolithic elastomer device (3D MED) to enhance the production rate of liquid droplets and gas bubbles. Based on double-sided imprinting technique, 3D microchannels architecture are formed in a monolayer elastomer that has one thousand parallel droplet/bubble generators. Because of the robustness of the microfluidic device, 3D MED could potentially be used for wide applications that require highly monodisperse droplets and bubbles.

Fabrication of Selective Anti-Biofouling Surface for Micro/Nanopatterning of Proteins

정헌호,이지혜,이창수,장홍철,양영헌,김온환,허강무 한국고분자학회 2010 Macromolecular Research Vol.18 No.9

This paper reports a simple method for creating a functionalized surface for the efficient micro/nanopatterning of proteins by micromolding in capillaries (MIMIC) of poly(ethylene glycol)-poly(lactide) diblock copolymer (PEG-PLA) and self-assembled polyelectrolyte multilayers (PEL). The fabricated surface consisted of two distinct regions: a PEL region to promote protein immobilization and a PEG-PLA background as a biological barrier to prevent the nonspecific binding of proteins. When the ability of anti-biofouling of PEG-PLA was compared with the most widely used blocking agents, such as bovine serum albumin (BSA) and skim milk, the PEG-PLA prevents the nonspecific adsorption of several proteins. The properties of a functionalized surface were characterized by the water contact angle and atomic force microscopy (AFM). Topological analysis clearly indicated that the MIMIC method provides a reliable surface regardless of the micro- and nanopattern size. Two different functionalities of the fabricated surface produce uniform protein patterns from the micro- to nanoscale with a high signal to noise ratio. The proposed method allows for flexibility in forming shapes, such as lines, squares, circles, triangles and stars, and can control the pattern size from 400 nm to 90 μm. Finally, the antigen-antibody assay showed good linearity over the range of 10 ng/mL to 25 μg/mL, indicating its feasibility for a quantitative measurement of the concentration of target proteins in a sample.

Microfluidic-assisted Production of Photocurable Polycaprolactone Microparticles for Efficient Treatment of Oily Wastewater

펑,정헌호 한국고분자학회 2022 한국고분자학회 학술대회 연구논문 초록집 Vol.47 No.1

미세유체장치를 이용한 생분해성 Polycarprolactone의단분산성 미세입자 생성제어

정헌호 한국청정기술학회 2019 청정기술 Vol.25 No.4

Monodisperse microparticles has been particularly enabling for various applications in the encapsulation anddelivery of pharmaceutical agents. The microfluidic devices are attractive candidates to produce highly uniform droplets thatserve as templates to form monodisperse microparticles. The microfluidic devices that have micro-scale channel allow precisecontrol of the balance between surface tension and viscous forces in two-phase flows. One of its essential abilities is togenerate highly monodisperse droplets. In this paper, a microfluidic approach for preparing monodisperse polycaprolactone(PCL) microparticles is presented. The microfluidic devices that have a flow-focusing generator are manufactured bysoft-lithography using polydimethylsiloxane (PDMS). The crucial factors in the droplet generation are the controllability ofsize and monodispersity of the microdroplets. For this, the volumetric flow rates of the dispersed phase of oil solution and thecontinuous phase of water to generate monodisperse droplets are optimized. As a result, the optimal flow condition for dropletdripping region that is able to generate uniform droplet is found. Furthermore, the droplets containing PCL polymer bysolvent evaporation after collection of droplet from device is solidified to generate the microparticle. The particle size can becontrolled by tuning the flow rate and the size of the microchannel. The monodispersity of the PCL particles is measured by a coefficient of variation (CV) below 5%. 단분산성 마이크로입자는 약물캡슐화 및 전달을 위한 다양한 응용분야에서 사용되고 있다. 미세유체장치는 매우 균일한 액적을 생산할 수 있는 중요한 장치이며 이 액적은 단분산성 마이크로입자를 생성할 수 있는 중요한 템플레이트(template)로의 역할을 한다. 미세유체장치는 마이크론 크기의 채널로 구성되어 표면장력과 점성력 간의 균형을 정교하게 조절할 수 있으며, 이는 단분산성 액적을 형성하는 필수적인 기술 중의 하나이다. 본 연구는 유동집적채널 기반의 미세유체장치에서 매우 균일한 polycaprolactone (PCL) 생분해성 고분자 입자를 제조하는 방법을 제안한다. 유동집적채널 기반의 미세유체장치는 polydimethylsiloxane (PDMS) 기반의 소프트리소그래피(soft-lithography) 방법을 통해 제작된다. 액적 생성에서 중요한요소는 마이크로 액적의 크기와 단분산성을 조절하는 것이다. 이를 위해, 본 연구에서는 이 미세유체장치에서 오일용액 분산상과 수용액 연속상의 부피유속을 제어하여 단분산성 액적 형성 조건을 최적화하였다. 그 결과 균일한 액적을 형성할 수있는 dripping 영역에 대한 최척화된 유속조건을 확인하였다. 그런 다음, 마이크로입자를 생성하기 위해 PCL 고분자를 포함한 액적을 장치에서 형성한 후 용매의 증발에 의해 입자화 하였다. 입자의 크기는 부피유속과 미세유체채널의 크기에 의해조절되며 입자의 단분산도는 변동계수(coefficient of variation, CV)값이 5% 이하로 제어될 수 있다.

Generation of Uniform Agarose Microwells for Cell Patterning by Micromolding in Capillaries

정헌호,이지혜,노영무,김윤곤,이창수 한국고분자학회 2013 Macromolecular Research Vol.21 No.5

We described a simple and facile method to generate uniform agarose microwells on a polyelectrolyte (PEL) multilayer functionalized surface for efficient and reliable cell patterning. The PEL multilayers, composed of polyallylamine hydrochloride (PAH) and polystyrene sulfonate ammonium (PSS), provide an adhesive environment,which promotes cell proliferation in live cell-based assays. Agarose microwells, which are able to selectively isolate cells into individual compartments, are fabricated by micromolding the agarose solution in capillaries (MIMIC). Moreover, the fabricated agarose microwells are able to effectively form different shapes (e.g., circles,triangles, squares, and stars) and can isolate multiple cell types (e.g., HEK 293, NIH3T3, and HepG2). We also demonstrated how this technique can be used for the real-time monitoring of communication between primary neuronal cells in the agarose microwells.

Microfluidic approach for mass production of monodisperse droplets

정헌호 한국공업화학회 2020 한국공업화학회 연구논문 초록집 Vol.2020 No.-

Emulsion and gas bubble has led to significant progress in varying area including materials synthesis, ultrasound imaging reagents, and biological high-throughput screening. One important challenge that may determine the commercial success and translation of microfluidic technologies is the mass production of monodisperse single and core-shell droplets/bubbles. In this work, we have developed a three-dimensional monolithic elastomer device (3D MED) to achieve the mass production of monodisperse single and core-shell droplets/bubbles. Based on double-sided imprinting technique, three dimensional microchannels architecture are formed in a single-sheet elastomer that has parallel droplet/bubble generators. Because of the scalable and robustness of the microfluidic device, 3D MED could potentially be used for wide applications that require highly monodisperse droplets and bubbles in the industry and research fields.

전해질 고분자 코팅 표면을 이용한 세포칩 제작

정헌호(Heon-Ho Jeong),송환문(Hwan-Moon Song),이창수(Chang-Soo Lee) 한국청정기술학회 2011 청정기술 Vol.17 No.1

본 연구 논문은 수용액 기반의 청정 표면 개질 기술을 이용하여 세포칩을 제작하는 방법에 관한 것이다. 세포칩의 활용범위는 유전학, 의생물학, 세포생물학등과 같은 기초학문과 더불어 암 진단 및 치료에 대한 유용한 도구로 응용 가능성을 가지게 된다. 기존의 세포 칩 제작을 위해서는 다량의 유기용매의 사용, 반도체 공정의 복잡성, 고가의 장비등을 사용함으로 인해 경제적 손실과 환경적 악영향을 주었다. 본 연구에서는 수용액 기반의 청정 표면 개질 기술과 마이크로컨택트프린팅 방법을 이용한 세포패터닝 기술을 융합하여 매우 손쉬운 세포칩 구현을 하는 기반 기술을 제시하였다. 이 세포칩을 이용하여 암세포와 정상 세포간의 세포표면에서 발현되는 다양한 탄수화물 및 그의 유도체의 발현양의 차이를 분석할 수 있었다. 이를 바탕으로 새로운 암진단 기술 및 기초 의공학 기술에 활용하고자 한다. This study presents a fabrication method of cell-chip using aqueous solution based surface modification. The applications of cell-chip have potential for fundamental study of genetics, cell biology as well as cancer diagnostics and treatment. Conventional methods for fabrication of cell-chip have been limited in economic loss and environmental pollution because of the use of harsh organic solvent, complex process of silicon technology, and expensive equipment. In order to fabricate cell chip, we have proposed simple and eco-friendly process combined polyelectrolyte multilayer coating with microcontact printing. For the proof of concept, the cell chip can be applied to analyze the different expression of cell surface glycans and derivatives between cancer and normal cells. Our proposed method is useful technique for the application of novel cancer diagnostics and basic medical engineering.

PDMS 블레이드 코팅법을 이용한 종이-기반 바이오센서칩 제작

정헌호 ( Heon-ho Jeong ),박차미 ( Chami Park ) 한국화학공학회 2021 Korean Chemical Engineering Research(HWAHAK KONGHA Vol.59 No.1

본 연구는 적은 비용으로 분석 장치 없이 질병 진단 및 경과를 모니터링할 수 있는 종이-기반 분석 장치(paper-based analytical device, PAD)를 제작하기 위해 polydimethylsiloxane (PDMS) 블레이드 코팅 방법을 제안하였다. PAD 디자인은 레이저 커팅 기술로 쉽게 몰드에 적용할 수 있으며, 제작된 몰드로 블레이드 코팅을 수행하여 완전한 소수성 장벽 형성에 필요한 조건을 확립하였다. 코팅 조건인 잉크의 두께와 종이와의 접촉시간에 따라 PDMS 소수성 장벽의 구조와 친수성 채널의 크기 변화를 분석하여 안정적으로 소수성 장벽을 형성할 수 있는 조건을 최적화하였다. 최적화된 방법을 바탕으로 PAD를 제작하여 특별한 분석기기 없이 단백질, 당, 메탈이온을 검출하여 바이오센서에 응용가능함을 증명하였다. This paper proposes the polydimethylsiloxane (PDMS) blade coating method for fabrication of paperbased analytical device (PAD) that is able to monitor the disease diagnosis and progress without special analytical equipment. The mold that has PAD design is easily modified by using laser cutting technique. And the fabricated mold is used for hydrophobic barrier formation by blade coating. We have optimized the stable formation of PDMS hydrophobic barrier as blade coating condition, which is established by analyzing the structure of the PDMS hydrophobic barrier and change of hydrophilic channel size as thickness of the ink and contact time with the chromatography paper. Based on optimal condition, we demonstrate that PAD as biosensor can apply to detect protein, glucose, and metal ion without special analysis equipment.

유동-집속 생성기의 병렬화를 통한 에멀젼 생산속도 향상

정헌호 ( Heon-ho Jeong ) 한국화학공학회 2018 Korean Chemical Engineering Research(HWAHAK KONGHA Vol.56 No.5

액적-기반 미세유체장치는 물질 합성 및 초고속 대용량 스크리닝 등 다양한 응용분야에서 변형 가능한 새로운 접근법을 이끌어 냈다. 그러나 단일의 액적생성기를 이용한 액적의 생성 속도가 매우 낮기 때문에 이를 상용화 하기 위해서는 생산속도를 높이기 위한 노력이 필요하다. 본 연구는 단일의 유동-집속 생성기를 병렬로 연결하여 단분산성 액적의 생성 속도를 높이는 방법에 관한 것이다. 이러한 액적생성기를 갖는 미세유체장치를 제작하기 위해 본 연구에서는 양면 임프린팅 방법을 이용하여 단층 엘라스토머 조각에3차원의 마이크로 채널을 갖는 3D 모놀리식 탄성중합체 장치(monolithic elastomer device, 3D MED)를 제작 할 수 있다. 이렇게 제작된 8개의 액적생성기가 연결된 3D MED를 이용하여 연속상과 분산상의 유체를 조절하여 단분산성 액적의 형성속도가 향상되었음을 증명하였다. 따라서 본 미세유체시스템을 사용하여 다양한 재료 또는 세포들을 함유하는 단분산성 액적을 형성하여 마이크로입자 제조 및 스크리닝 시스템과 같은 넓은 분야에 활용될 수 있을 것으로 기대된다. Droplet-based microfluidic device has led to transformational new approaches in various applications including materials synthesis and high-throughput screening. However, efforts are required to enhance the production rate to industrial scale because of low production rate in a single droplet generator. In here, we present a method for enhancing production rate of monodisperse droplets via parallelization of flow-focusing generators. For this, we fabricated a three-dimensional monolithic elastomer device (3D MED) that has the 3D channel structures in a single layer, using a double-sided imprinting method. We demonstrated that the production rate of monodisperse droplet is increased by controlling the flow rate of continuous and dispersed phases in 3D MED with 8 droplet generators. Thus, we anticipate that this microfluidic system will be used in wide area including microparticle synthesis and screening system via encapsulation of various materials and cells in monodisperse droplets.

PDMS와 고분자 전해질 표면을 이용한 간편한 세포 패터닝 방법

정헌호(Heon-Ho Jeong),송환문(Hwan-Moon Song),황예진(Ye-jin Hwang),황택성(Taek-Sung Hwang),이창수(Chang-Soo Lee) 한국생물공학회 2009 KSBB Journal Vol.24 No.6

This study presented facile method of cell patterning using fabricated PDMS patterns on polyelectrolyte coated surface. This basic principle is the fabrication of functional surface presenting two orthogonal surfaces such as cell adhesive and repellent properties. Cell adhesive surface was firstly fabricated with simple coating of polyelectrolyte multilayer. And then, the desired patterns of PDMS for the prevention of nonspecific binding of cells were transferred onto the previously formed thin film of polyelectrolyte multilayer. Thus, we could prepare novel functional surface simultaneously containing PDMS and polyelectrolyte region. As expected, the PDMS regions showed effective prevention of nonspecific binding of cell and the other region, exposed polyelectrolyte area, provided cell adhesive environment. The height of formed PDMS structure was about 100 nm. Based on this method, cell patterning can be successfully obtained with various pattern shapes and sizes. Therefore, we expect that this simple method will be useful platform technology for the development of cell chip, cell based assay system, and biochip.