Lin,Keng-hui / Associate Research Fellow

Research Interest

• Experimental Soft Condensed Matter Physics
• Microfluidics
• Nano- and micro- material Assembly
• Biophysics
• Tissue Engineering
• 3D Cell Culture
• Mechanics of Solid Foam

獎項及殊榮

Experience

• Postdoc, Dept. of Chemistry and Chemical Biology, Harvard University
• Visiting Scholar, Harvard University
• Assistant Research Fellow, Academia Sinica (2004-2011)
• Associate Research Fellow, Institute of Physics, Academia Sinica (2011-Current)
• Adjunct Associate Professor, National Central University (2005-2011)

Publication

Journal Papers

• [1]     Kao TW, Chiou A, Lin KH, Liu YS, Lee OK, 2021, “Alteration of 3D Matrix Stiffness Regulates Viscoelasticity of Human Mesenchymal Stem Cells.”, International journal of molecular sciences, 22(5), 2441. (SCIE) (IF: 5.924; SCI ranking: 22.6%,27.4%)
  
  
• [2]     Lin Jong-Wei, Huang Yi-Man, Chen Yin-Quan, Chuang Ting-Yun, Lan Tien-Yun, Liu Yen-Wenn, Pan Hung-Wei, You Li-Ru, Wang Yang-Kao, Lin Keng-hui, Chiou Arthur, Kuo Jean-Cheng, 2021, “Dexamethasone accelerates muscle regeneration by modulating kinesin-1-mediated focal adhesion signals”, Cell Death Discovery, 7(1), 35. (SCIE) (IF: 5.241; SCI ranking: 39%)
  
  
• [3]     Huang CK, Paylaga GJ, Bupphathong S, Lin KH, 2020, “Spherical microwell arrays for studying single cells and microtissues in 3D confinement.”, Biofabrication, 12(2), 025016. (SCIE) (IF: 10.02; SCI ranking: 7.8%,7.3%)
  
  
• [4]     Cheng-Nan Yang, Li-Syuan Liang, Keng-hui Lin, Wen-Yea Jang, 2019, “The mechanical properties of monodisperse foam scaffolds”, Composites Part B: Engineering, 164, 517-523.
  
  
• [5]     Lin Han-Yuan, Chu Li-An, Yang Hsuan, Hsu Kuo-Jen, Lin Yen-Yin, Lin Keng-Hui*, Chu Shi-Wei*, Chiang Ann-Shyn*, 2019, “Imaging through the Whole Brain of Drosophila at λ/20 Super-resolution”, iScience, 14, 164-170. (SCIE) (IF: 5.458; SCI ranking: 19.2%)
  
  
• [6]     Doss BL, Rahmani Eliato K, Lin KH, Ros R, 2019, “Quantitative mechanical analysis of indentations on layered, soft elastic materials”, Soft matter, 15(8), 1776-1784. (SCIE) (IF: 3.679; SCI ranking: 46.9%,43.8%,26.7%,28.6%)
  
  
• [7]     Guo-wei Jheng, Sung Sik Hur, Chia-ming Chang, Jia-Shing Cheng, Hsiao-hui Lee, Bon-chu Chung, Yang-kao Wang, Keng-hui Lin, Juan C. del Alamo, Shu Chien, Jin-wu Tsai*, 2018, “Lis1 dysfunction leads to traction force reduction and cytoskeletal disorganization during cell migration.”, Biochemical and biophysical research communications, 497(3), 869-875. (SCIE) (IF: 3.575; SCI ranking: 58.2%,41.7%)
  
  
• [8]     Han J, Lin KH, Chew LY, 2017, “Study on the regulation of focal adesions and cortical actin by matrix nanotopography in 3D environment.”, Journal of physics. Condensed matter : an Institute of Physics journal, 29(45), 455101.
  
  
• [9]     Chen-chie Wang, Kai-chiang Yang, Keng-hui Lin, Yen-liang Liu, Ya-Ting Yang, Tzong-Fu Kuo, Ing-Ho Chen, 2016, “Expandable Scaffold Improves Integration of Tissue-Engineered Cartilage: An In Vivo Study in a Rabbit Model.”, TISSUE ENGINEERING, 22(11-12), 873-84.
  
  
• [10]     Chen-en Wu, Keng-hui Lin, Jia-yang Juang, 2016, “Hertzian load-displacement relation holds for spherical indentation on soft elastic solids undergoing large deformations”, TRIBOLOGY INTERNATIONAL, 97, 71-76. (SCIE) (IF: 4.872; SCI ranking: 12.6%)
  
  
• [11]     Yin-Ping Lo, Yi-Shiuan Liu, Marilyn G. Rimando, Jennifer Hui-Chun Ho, Keng-hui Lin and Oscar K. Lee*, 2016, “Three-dimensional spherical spatial boundary conditions differentially regulate osteogenic differentiation of mesenchymal stromal cells”, SCIENTIFIC REPORTS, 6, 21253. (SCIE) (IF: 4.38; SCI ranking: 23.3%)
  
  
• [12]     Wen-Ting Hsieh, Yi-Shuan Liu, Yi-hsuan Lee, Rimando, Marilyn Rimando, Keng-hui Lin*, Oscar K. Lee*, 2016, “Matrix dimensionality and stiffness cooperatively regulate osteogenesis of mesenchymal stromal cells”, ACTA BIOMATERIALIA, 32, 210. (SCIE) (IF: 8.947; SCI ranking: 11.1%,12.2%)
  
  
• [13]     Bishnubrata Patra, Yu-Sheng Peng, Chien-Chung Peng, Wei-Hao Liao, Yu-An Chen, Keng-Hui Lin, Yi-Chung Tung, Chau-Hwang Lee, 2014, “Migration and vascular lumen formation of endothelial cells in cancer cell spheroids of various sizes”, Biomicrofluidics, 8(5), 052109. (SCIE) (IF: 2.8; SCI ranking: 59%,58.3%,72.9%,29.4%)
  
  
• [14]     Chen-chie Wang, Kai-Chiang Yang, Keng-hui Lin, Chang-chin Wu, Yen-liang Liu, Feng-Huei Lin, Ing-ho. Chen, 2014, “A biomimetic honeycomb-like scaffold prepared by flow-focusing technology for cartilage regeneration.”, Biotechnology and bioengineering, 111(11), 2338-48. (SCIE) (IF: 4.53; SCI ranking: 27.5%)
  
  
• [15]     Thai-Yen Ling, Yen-Liang Liu, Yung-Kang Huang, Sing-Yi Gu, Hung-Kuan Chen, Choa-Chi Ho, Po-Nien Tsao, Yi-Chung Tung, Huei-Wen Chen, Chiung-Hsiang Cheng, Keng-Hui Lin, Feng-Huei Lin, 2014, “Differentiation of lung stem/progenitor cells into alveolar pneumocytes and induction of angiogenesis within a 3D gelatin--microbubble scaffold.”, Biomaterials, 35(22), 5660-9. (SCIE) (IF: 12.479; SCI ranking: 3.3%,4.9%)
  
  
• [16]     Yi-hsuan Lee, Jung-ren Huang, Yang-kao Wang, and Keng-hui Lin*, 2013, “Three-dimensional fibroblast morphology on compliant substrates of controlled negative curvature ”, Integrative Biology, 5(12), 1447. (SCIE) (IF: 2.192; SCI ranking: 86.2%)
  
  
• [17]     Yung-Shin Sun, Shih-Wei Peng, Keng-Hui Lin, and Ji-Yen Cheng, 2012, “Electrotaxis of lung cancer cells in ordered three-dimensional scaffolds”, Biomicrofluidics, 6(1), 14102. (SCIE) (IF: 2.8; SCI ranking: 59%,58.3%,72.9%,29.4%)
  
  
• [18]     Chen-Chie Wang, Kai-Chiang Yang, Keng-Hui Lin, Yen-Liang Liu, Hwa-Chang Liu, Feng-Huei Lin, 2012, “Cartilage regeneration in SCID mice using a highly organized three-dimensional alginate scaffold.”, Biomaterials, 33(1), 120-7. (SCIE) (IF: 12.479; SCI ranking: 3.3%,4.9%)
  
  
• [19]     Chen-chie Wang, Kai-chiang Yang, Keng-hui Lin, Hwa-Chang Liu, Feng-huei Lin*, 2011, “A highly organized three-dimensional alginate scaffold for cartilage tissue engineering prepared by microfluidic technology.”, Biomaterials, 32(29), 7118-26. (SCIE) (IF: 12.479; SCI ranking: 3.3%,4.9%)
  
  
• [20]     Jing-ying Lin, Wan-jung Lin, Wei-hong Hong, Hsiang-haw Ning, Wei-chun Hung, Stephanie H. Nowotarski, Susana Montenegro Gouveia, Ines Cristo, and Keng-hui Lin*, 2011, “Morphology and organization of tissue cells in 3D microenvironment of monodisperse foam scaffolds”, SOFT MATTER, 7, 10010. (SCIE) (IF: 3.679; SCI ranking: 46.9%,43.8%,26.7%,28.6%)
  
  
• [21]     Chi-Chih Ho, Po-Yuan Chen, Keng-Hui Lin, Wen-Tau Juan, Wei-Li Lee, 2011, “Fabrication of Monolayer of Polymer/Nanospheres Hybrid at a Water-Air Interface.”, ACS applied materials & interfaces, 3(2), 204. (SCIE) (IF: 9.229; SCI ranking: 13.1%,19.6%)
  
  
• [22]     Chi-chih Ho, Tung-wu Hsieh, Hsiang-Hsi Kung, Wen-Tau Juan, Keng-Hui Lin, and Wei-Li Lee, 2010, “Reduced Saturation Magnetization in Cobalt Antidot Thin Films Prepared by polyethylene oxide-assisted self-assembly of polystyrene nanospheres”, Applied Physics Letter, 96, 122504.
  
  
• [23]     Kuo-yuan Chung, Narayan Chandra Mishra, Chen-chi Wang, Feng-hui Lin, and Keng-hui Lin*, 2009, “Fabricating Scaffolds by Microfluidics”, Biomicrofluidics, 3(2), 022403. (SCIE) (IF: 2.8; SCI ranking: 59%,58.3%,72.9%,29.4%)
  
  
• [24]     Po-Keng Lin, Keng-hui Lin, Chi-Cheng Fu, K.-C. Lee, Pei-Kuen Wei, Woei-Wu Pai, Pei-Hsi Tsao, Y.-L. Chen and W. S. Fann, 2009, “One-Dimensional Dynamics and Transport of DNA Molecules in a Quasi-Two-Dimensional Nanoslit”, Macromolecules, 42,1770-1774. (SCIE) (IF: 5.985; SCI ranking: 8.8%)
  
  
• [25]     Keng-hui Lin*, Liang-jie Lai, Chih-chung Chang, and Hui Chen, 2008, “Assembly of Microspheres with Polymers by Evaporating Emulsion Droplets”, PHYSICAL REVIEW E, 78, 041408. (SCIE) (IF: 2.529; SCI ranking: 35.3%,14.5%)
  
  
• [26]     Wang WU, Chen C,Lin KH, Fang Y, Lieber CM, 2005, “Label-free detection of small-molecule-protein interactions by using nanowire nanosensors.”, Proceedings of the National Academy of Sciences of the United States of America, 102(9), 3208-12. (SCIE) (IF: 11.205; SCI ranking: 11%)
  
  
• [27]     Islam MF, Lin KH, Lacoste D, Lubensky TC, Yodh AG, 2003, “Field-induced structures in miscible ferrofluid suspensions with and without latex spheres.”, Physical review. E, Statistical, nonlinear, and soft matter physics, 67(2 Pt 1), 021402.
  
  
• [28]     M.C. McAlpine, R.S. Friedman, S. Jin, K.H. Lin, W.U. Wang, C.M. Lieber, 2003, “High-performance nanowire electronics and photonics on glass and plastic substrates”, NANO LETTERS, 3(11), 1531-1535. (SCIE) (IF: 11.189; SCI ranking: 11.2%,13.6%,9.5%,14%,9.4%,15.9%)
  
  
• [29]     Mach P, Wiltzius P, Megens M, Weitz DA, Lin Kh KH, Lubensky TC, Yodh AG, 2002, “Electro-optic response and switchable Bragg diffraction for liquid crystals in colloid-templated materials.”, Physical review. E, Statistical, nonlinear, and soft matter physics, 65(3 Pt 1), 031720.
  
  
• [30]     Peter Mach, P. Wiltzius, M. Megens, D. A. Weitz, Keng-hui Lin, T. C. Lubensky, Arjun G. Yodh, 2002, “Electro-optic response and switchable Bragg diffraction for liquid crystals in colloid-templated materials.”, PHYSICAL REVIEW E, 58, 679. (SCIE) (IF: 2.529; SCI ranking: 35.3%,14.5%)
  
  
• [31]     Lau AW, Lin KH, Yodh AG*, 2002, “Entropic interactions in suspensions of semiflexible rods: short-range effects of flexibility.”, Physical review. E, Statistical, nonlinear, and soft matter physics, 66(2 Pt 1), 020401.
  
  
• [32]     J. Zhang, A. Alsayed, Keng-hui Lin, S. Sanyal, F. Zhang, W-J. Pao, V. S. K. Balagurusamy, P. A. Heiney, and A. G. Yodh, 2002, “Template-Directed Convective Assembly of 3D Face-Centered-Cubic Colloidal Crystals ”, APPLIED PHYSICS LETTERS, 81, 3176. (SCIE) (IF: 3.791; SCI ranking: 29.4%)
  
  
• [33]     Keng-hui Lin, John C. Crocker, Ana C. Zeri, Arjun G. Yodh*, 2001, “Colloidal interactions in suspensions of rods.”, PHYSICAL REVIEW LETTERS, 87(8), 088301. (SCIE) (IF: 9.161; SCI ranking: 8.1%)
  
  
• [34]     A.G. Yodh, Keng-hui Lin, J. C. Crocker, A. D. Dinsmore, R. Verma, and P. D. Kaplan, 2001, “Entropically Driven Self-Assembly and Interaction in Suspension”, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES, 359, 921. (SCIE) (IF: 4.226; SCI ranking: 24.7%)
  
  
• [35]     Keng-hui Lin, John C. Crocker, Vikram V. Prasad, Andrew Schofield, David A. Weitz, T. C. Lubensky, Arjun G. Yodh*, 2000, “Entropically driven colloidal crystallization on patterned surfaces”, PHYSICAL REVIEW LETTERS, 85(8), 1770-1773. (SCIE) (IF: 9.161; SCI ranking: 8.1%)
  
  

Others

• [1]     林耿慧，2005，〈膠體粒子的布朗運動〉，《物理雙月刊》，第 27 卷 3 期 470-474。
  
  

發現與突破

• [1]     西元年：2020
  研究人員(中)：林耿慧
  研究人員(英)：LIN, KENG-HUI
  研究成果名稱(中)：圓洞井作為三維培養基材
  研究成果名稱(英)：Spherical microwell for 3D cell culture
  簡要記述(中)：林耿慧實驗室近期開發出更新一代的三維細胞培養平台，由圓洞陣列所組成。這個圓洞陣列使用方式非常多樣化，如當圓洞陣列都沒有讓細胞貼附處時，細胞能在圓洞內聚集成類球體結構(spheroid)，但圓洞開口比直徑小，所以球體結構不會掉出來。當只有圓洞內有貼附處時，細胞會被限制在圓洞內，無法爬行出來。他們發現，當纖維母細胞被限制在 100 微米以下的圓洞，細胞就停止分裂，這是第一次展示利用很明確的三維幾何空間來改變細胞週期。這個文章發表在 Biofabrication 12, 025016 (2020)。
  簡要記述(英)：Microwell arrays have emerged as three-dimensional substrates for cell culture due to their simplicity of fabrication and promise for high-throughput applications such as 3D cell-based assays for drug screening. To date, most microwells have had cylindrical geometries. Motivated by our previous findings that cells display 3D physiological characteristics when grown in the spherical micropores of monodisperse foam scaffolds (Lee et al 2013 Integr. Biol. 5 1447–55 and Lin et al 2011 Soft Matter 7 10010–6), here we engineered novel microwells shaped as spherical caps with obtuse polar angles, yielding narrow apertures. When used as bare substrates, these microwells were suitable for culturing cell spheroids; the narrow apertures sterically hindered unattached cultured cells from rolling out of microwells under agitation. When only the walls of the microwell were conjugated with extracellular matrix proteins, cells remained confined in the microwells. Epithelial cells proliferated and burst out of the aperture, and cell polarity was oriented based on the distribution of extracellular matrix proteins in the microwells. Surprisingly, single fibroblast cells in spherical wells of various diameters (40–100 μm) underwent cell-cycle arrest, while cells in circular cylindrical microwells continued to proliferate. Spatial confinement was not sufficient to cause cell-cycle arrest; however, confinement in a constant negative-curvature microenvironment led to cell-cycle arrest. Overall, these investigations demonstrate that this spherical microwell substrate constitutes a novel basic research tool for elucidating how cells respond to dimensionality and microenvironment with radii of curvature at the cellular length scale.
  
  
  
• [2]     西元年：2013
  研究人員(中)：林耿慧、李怡萱
  研究人員(英)：LIN, KENG-HUI, Yi-hsuan Lee
  研究成果名稱(中)：藉由可調節軟硬度的三維均一孔洞鷹架來了解細胞在三維感測的軟硬度
  研究成果名稱(英)：The response of cell to the stiffness of 3D compliant scaffold of uniform pores
  簡要記述(中)：設計一個適合在三維環境研究細胞與基材的鷹架是了解三維細胞行為的關鍵. 過去十幾年因為新型可調節軟硬度的二維細胞培養基材的發明, 帶動科學家對細胞力學的研究, 我們把這可調節軟硬度的基材做成三維.我們利用纖維母細胞作為模型系統, 藉由分析他們型態的伸長量, 來量化他們對周圍環境軟硬度的反應. 我們也發現在洞裡, 細胞黏著分子與骨架的分布與二維的細胞很不同.
  簡要記述(英)：Designing biomaterials for studying cell-extracellular matrix (ECM) interactions in three dimensions (3D) is key to the biological relevance of observations of cells grown in 3D culture. In recent decades, novel two-dimensional substrates such as compliant gels with patterned proteins have provided many useful insights into how adhesive and mechanical cues drive cellular behavior. Here, we extend cell culture into the third dimension by engineering uniform pores in compliant gels; these pores are treated with fibronectin to pattern ECM proteins as a spherical shell. The rigidity of the 3D microenvironment is controlled by choice of base gels used to assemble the scaffolds. Fibroblasts exhibit quantitative differences in morphology and cytoskeletal architecture following culture in our 3D scaffolds versus 2D substrates. Our new technology offers independent control over factors such as three-dimensionality, curvature, biochemical composition, and the mechanical stiffness of the substrate, all of which make critical contributions to the formation of cell adhesions in 3D.
  

  主要相關著作：

  Yi-hsuan Lee, Jung-ren Huang, Yang-kao Wang, and Keng-hui Lin*, 2013, “Three-dimensional fibroblast morphology on compliant substrates of controlled negative curvature ”, Integrative Biology, 5(12), 1447. (SCIE) (IF: 2.192; SCI ranking: 86.2%)

  
  
  
• [3]     西元年：2010
  研究人員(中)：林耿慧
  研究人員(英)：LIN, KENG-HUI
  研究成果名稱(中)：不同組織細胞在相同三維圓形孔洞材料的型態與組織
  研究成果名稱(英)：Organization and Morphology of Tissue Cells in Ordered Cellular Solids
  簡要記述(中)：我們改進之前微流體通道製作三維鷹架的製作 - 選擇細胞喜歡貼覆的吉利丁材質, 並且改變微流體通道的製作與收集方法. 這樣製作出來的鷹架能有更大的範圍. 我們在相同的三維微環境中養三種不同組織的細胞,表皮細胞會極化形成囊腫狀, 肌肉細胞會呈纖維狀, 纖維母細胞會有各種不同於二維成長的形狀.
  簡要記述(英)：We demonstrate high-throughput fabrication of gelatin-based ordered cellular solids with tunable pore size and solid fraction. This process involves
  generating high air fraction and monodisperse liquid foam with a flow-focusing microfluidic device. The monodisperse liquid foam was further processed into open-cell solid foam, which was used as tissue-engineering scaffolds for cell culture. Three distinct cell types were cultured under these conditions and displayed appropriate physiological, morphological, and functional
  characteristics. Epithelial cells formed cyst-like structures and were
  polarized inside pores, myoblasts adopted a tubular structure and fused into myotubes, and fibroblasts exhibited wide varieties of morphologies depending
  on their location inside the scaffolds. These ordered cellular solids therefore make possible the study of pore-size effects on cells and the investigation of mechanical properties of microscopic foam structures.
  
  
  
• [4]     西元年：2009
  研究人員(中)：林耿慧
  研究人員(英)：LIN, KENG-HUI
  研究成果名稱(中)：利用微流體通道製作組織工程鷹架
  研究成果名稱(英)：Fabricating Scaffolds by Microfluidics
  簡要記述(中)：一般細胞在身體組織裡是生長在一個三維環境, 所以在三維環境下培養細胞是了解細胞如何形成組織的關鍵,在組織工程裡, 科學家製作了各種鷹架來做這件事. 但要有系統性的去了解細胞環境對細胞的影響, 鷹架的孔洞均一性就很重要.我們利用微流體通道來生產大小相同的泡泡, 這些泡泡會堆疊成有序的晶格結構, 我們用這做為樣板, 把泡泡結構變成多孔性開放的固體材料, 並做為鷹架. 在這樣的鷹架上培養細胞, 並觀察它們生長, 發現優於傳統不均勻的鷹架. 我們相信, 這個方法在三維細胞培養與了解細胞固體的力學性質的研究上有很大的應用.
  簡要記述(英)：Tissue cells in the body grow in a three-dimensional mesh called an extracellular matrix. It is important to create a 3D environment for the study of tissue formation. In tissue engineering, scientists fabricate all kinds of scaffold to achieve this purpose. However, to study the cell-matrix interaction systematically, it is important to have a uniform scaffold. We utitlize the microfluidic to generate monodisperse bubbles which assemble into crystalline structures. We use the foam crystal as a template and then turn it into porous gel of uniform pore size. We culture cells inside the uniform solid foam and the cell proliferate faster in comparison with the traditional non-uniform scaffold. We believe this method is very useful in the studies of 3D cell cultures and cellular solids.
  

  主要相關著作：

  Kuo-yuan Chung, Narayan Chandra Mishra, Chen-chi Wang, Feng-hui Lin, and Keng-hui Lin*, 2009, “Fabricating Scaffolds by Microfluidics”, Biomicrofluidics, 3(2), 022403. (SCIE) (IF: 2.8; SCI ranking: 59%,58.3%,72.9%,29.4%)