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CellTrans researchers have contributed to the development of “lab-on-a-chip” in vitro tools that facilitate functional imaging of the complex physiology of human pancreatic islets. Macro-scale perifusion apparatuses were developed in the 1970s to understand the hormone secretion kinetics; however, these apparatuses had limitations such as limited flow control, inadequate mimicking of the in vivo microenvironment, a lack of integration with imaging tools, as well as high costs. Since 2009, our laboratory has developed microfluidic-based perifusion and imaging systems. Some advantages of these biochips include minimizing the consumption of reagents and analytes, better control of flow phenomena at micro-scale, easier integration of new imaging modalities, and suitability for high throughput and high content multimodal analysis. Thus far, we have developed a series of microfluidic biochips that can be applied to study the physiology of islets, single beta-cells, microcapsulated islets/beta-cells, and beta-cell like stem cells.

Microfluidic Device Development

A microfluidic disc-on-a-chip device for mouse intervertebral disc—pitching a next generation research platform to study disc degeneration. Jun Dai, Yuan Xing, Li Xiao, Jingyi Li, Ruofan Cao, Yi He, Huang Fang, Ammasi Periasamy, Jose Oberhozler, Li Jin, James P. Landers, Yong Wang, Xudong Li.  ACS Biomaterials Science & Engineering. Feburary, 2019.

A Pumpless Microfluidic Device Driven by Surface Tension for Pancreatic Islet Analysis. Yuan Xing, Mohammad Nourmohammadzadeh, Joshua E. Mendoza Elias, Manwai Chan, Zequn Chen, James J. McGarrigle, José Oberholzer, and Yong Wang. Biomed Microdevices. 2016 Oct;18(5):80. PMID: 27534648.

Microfluidic Array for Real-Time Live-Cell Imaging of Human and Rodent Pancreatic Islets. Mohammad Nourmohammadzadeh, Yuan Xing, Jin Wuk Lee, Matthew A. Bochenek, Joshua E. Mendoza-Elias,  James J. McGarrigle, Enza Marchese, Yeh, Chun-Chieh,  David T. Eddington,  José Oberholzer,  and Yong Wang. Lab on a Chip. 2016, 16, 1466 – 1472. PMID: 26999734.

Microfluidic Array with Integrated Oxygenation Control for Real-Time Live-Cell Imaging: Effect of Hypoxia on Physiology of Microencapsulated Pancreatic Islets. Mohammad Nourmohammadzadeh, Joe F Lo, Matt Bochenek, Joshua E. Mendoza-Elias, Qian Wang, Ze Li, Feng Feng, Merigeng Qi, David Eddington, José Oberholzer, Yong Wang. Analytical Chemistry, October, 2013. PMID: 24083835.

Quantitative and Temporal Control of Oxygen Microenvironment at the Single Islet Level. Joe F. Lo, Wang Yong, David T. Eddington, Jose Oberholzer. J Vis Exp. 2013. PMID: 24299958.

Application of Microfluidic Technology for Studying Islet Physiology and Pathophysiology. Yong Wang, Joshua E. Mendoza-Elias, James J. McGarrigle, Mohammad Nourmohammadzadeh, Qian Wang, Ze Li, Feng Feng, Merigeng Qi, Joe F. Lo, David T. Eddington, and José Oberholzer. Micro and Nanosystem. 5(3), 2013 Aug: 216-223.

Studying Islet Pathophysiology via Microfluidic Control of Hypoxia. Joe Fu-Jiou Lo, Yong Wang, Jose Oberholzer, David Thomas Eddington. Micro and Nanosystem. 5(3), 2013 Aug: 209-215.

Islet Preconditioning via Multimodal Microfluidic Modulation of Intermittent Hypoxia. Lo JF, Wang Y, Blake A, Yu G, Harvat TA, Jeon H, Oberholzer J, Eddington DT. Analytical Chemistry. February 2012. PMID: 22296179.

Systematic Prevention of Bubble Formation and Accumulation for Long-Term Culture of Pancreatic Islet Cells in Microfluidic Device. Wang Y, Lee D, Zhang L, Jeon H, Mendoza-Elias JE, Harvat TA, Hassan SZ, Zhou A, Eddington DT, Oberholzer J. Biomed Microdevices. January, 2012. PMID: 22252566.

Dual Microfluidic Perifusion Networks for Concurrent Islet Perifusion and Optical Imaging. Lee D, Wang Y, Mendoza-Elias JE, Adewola AF, Harvat TA, Kinzer K, Gutierrez D, Qi M, Eddington DT, Oberholzer J. Biomed Microdevices. August, 2011. PMID: 21850483.

Application of Microfluidic Technology to Pancreatic Islet Research: First Decade of Endeavor. Wang Y, Lo JF, Mendoza-Elias JE, Adewola AF, Harvat TA, Kinzer KP, Lee D, Qi M, Eddington DT, Oberholzer J. Bioanalysis. October,2010. Review.PMID:21083325.

Size-Based Separation and Collection of Mouse Pancreatic Islets for Functional Analysis. Nam KH, Yong Wang, Harvat T, Adewola A, Wang S, Oberholzer J, Eddington DT. Biomed Microdevices. October, 2010. PMID:20549367.

Microfluidic Perifusion and Imaging Device for Multi-Parametric Islet Function Assessment. Adewola AF, Lee D, Harvat T, Mohammed J, Eddington DT, Oberholzer J, Wang Y. Biomed Microdevices. June, 2010. PMID:20300858.

A Multi-Parametric Islet Perifusion System within a Microfluidic Perifusion Device. Adewola AF, Wang Y, Harvat T, Eddington DT, Lee D, Oberholzer J. J Vis Exp. January, 2010.PMID:20104201.

Microfluidic Device for Multimodal Characterization of Pancreatic Islets. Mohammed JS, Wang Y, Harvat TA, Oberholzer J, Eddington DT. Lab Chip. January, 2009. PMID:19209341.

Microfluidic Application

Genetically Encoded, Photostable Indicators to Image Dynamic Zn2+ Secretion of Pancreatic Islets. Minghai Chen, Shen Zhang, Yuan Xing, Xinyu Li, Yi He, Yong Wang, José Oberholzer, and Hui-wang Ai.  Analytical Chemistry. September, 2019. PMID:31475537

FLIM imaging of auto-fluorescent NAD(P)H and FAD to track metabolic changes of non-adherent leukemia cells using microfluidic trapping array. Ruofan Cao; Horst Wallrabe; Chunbo Huang; Su-Fern Tan; David Feith; David Feith; Yuan Xing; Yong Wang; Jose Oberholzer; Mark Kester; Thomas P. Loughran; Ammasi Periasamy. SPIE proceeding, March,2019

Toll-like receptors 2 and 4 act as brakes to regulate adaptive β-cell mass expansion in diet-induced obesity. Yewei Ji, Shengyi Sun, Neha Shrestha, Laurel Darragh, Jun Shirakawa, Yuan Xing, Yi He, Bethany A. Carboneau, Hana Kim, Duo An, Minglin Ma, Jose Oberhozler, Scott A. Soleimanpour, Maureen Gannon, Chengyang Liu, Ali Naji, Rohit N. Kulkarni, Yong Wang, Sander Kersten, and Ling Qi. Nature Immunology. 2019 Jun;20(6):677-686.PMID: 311103

Recapitulating endocrine cell clustering promotes formation of mature beta cells from human stem cells. Gopika G. Nair, Jennifer S. Liu, Holger A. Russ, Stella Tran, Michael S. Saxton, Richard Chen, Charity Juang, Mei L. Lan, Sapna Puri, Yuan Xing, Yong Wang, Vinh Q. Nguyen1, Gregory Szot, Jose Oberholzer, Anil Bhushan, and Matthias Hebrok. Nature Cell Biology. 2019 Feb;21(2):263-274. PMID:30710150

In situ graphene liquid cell-transmission electron microscopy study of insulin secretion in pancreatic islet cells. Firlar E, Ouy M, Covnot L, Xing Y, Lee D, Chan A, He Y, Song B, Afelik S, Wang Y, Shahbazian-Yassar R, Oberholzer J, Shokuhfar T.  International Journal of Nanomedicine. 2019 Jan 7;14:371-382. PMID:30662261

Beta Cell Replacement in Mice Using Human Type 1 Diabetes Nuclear Transfer Embryonic Stem Cells. Sui L, Danzl N, Campbell SR, Viola R, Williams D, Xing Y, Wang Y, Phillips N, Poffenberger G, Johannesson B, Oberholzer J, Powers AC, Leibel RL, Chen X, Sykes M, Egli D. Diabetes. 2017 Sep 20. PMID:28931519

Converting Adult Pancreatic Islet α Cells into β Cells by Targeting Both Dnmt1 and Arx. Chakravarthy H, Gu X, Enge M, Dai X, Wang Y, Damond N, Downie C, Liu K, Wang J, Xing Y, Chera S, Thorel F, Quake S, Oberholzer J, MacDonald PE, Herrera PL, Kim SK. Cell Metab. 2017 Feb 12. PMID: 28215845

Induction of miR-132 and miR-212 Expression by Glucagon-Like Peptide 1 (GLP-1) in Rodent and Human Pancreatic β-Cells. Jin Shang, Jing Li, Mark P. Keller, Hans E. Hohmeier, Yong Wang, Yue Feng, Heather H. Zhou, Xiaolan Shen, Mary Rabaglia, Mufaddal Soni, Alan D. Attie, Christopher B. Newgard, Nancy A. Thornberry, Andrew D. Howard, and Yun-Ping Zhou. Molecular Endocrinology. July, 2015. PMID: 26218441

Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates. Omid Veiseh, Joshua C. Doloff, Minglin Ma, Arturo J. Vegas, Hok Hei Tam, Andrew Bader, Jie Li, Erin Langan, Jeffrey Wyckoff, Whitney S. Loo, Siddharth Jhunjhunwala, Alan Chiu, Sean Siebert, Katherine Tang, Jennifer Hollister-Lock, Stephanie Aresta-Dasilva, Matthew Bochenek, Joshua Mendoza-Elias, Yong Wang, Merigeng Qi, Danya M. Lavin, Nimit Dholakia, Raj Thakrar, Gordon C. Weir, Jose Oberholzer, Dale L. Greiner, Robert Langer, and Daniel G. Anderson. Nature Materials. April, 2015. PMID: 25985456

IG20/MADD Plays a Critical Role in Glucose-Induced Insulin Secretion. Liang-cheng Li, Yong Wang, Ryan Carr, Christine Samir Haddad, Ze Li, Lixia Qian, Jose Oberholzer, Ajay V. Maker, and Bellur S. Prabhakar. Diabetes. December, 2013. PMID: 24379354

Diazoxide, a KATP Channel Opener, Prevents Ischemia-Reperfusion Injury in Rodent Pancreatic Islets. Yong Wang, Shusen Wang, Tricia Harvat, Katie Kinzer, Lisa Zhang, Feng Feng, Meirigeng Qi, Jose Oberholzer. Cell Transplantation. September, 2013. PMID: 24070013

Overexpression of E2F3 Promotes Proliferation of Functional Human Beta-Cells without Induction of Apoptosis. Brian Rady, Yanmei Chen, Pilar Vaca, Qian Wang, Yong Wang, Patrick Salmon, José Oberholzer. Cell Cycle. August, 2013. PMID: 23907129

Modified Gold Nanoparticle Vectors: a Biocompatible Intracellular Delivery System for Pancreatic Islet Cell Transplantation.Vega RA, Wang Y, Harvat T, Wang S, Qi M, Adewola AF, Lee D, Benedetti E, Oberholzer J. Surgery. October, 2010. PMID:20800254


Microfluidic devices for biomedical applications. Part 5: Chapter 16: Development of microfluidic strategy for evaluating human islet potency and viability prior to transplant. Yong Wang, Joshua E. Mendoza-Elias, Joe F. Lo, Tricia A. Harvat, Feng Feng, Ze Li, Qian Wang, Mohammad Nourmohammadzadeh, Diana Gutierrez, Merigeng Qi, David T. Eddington, and José Oberholzer. November, 2013. Woodhead Publishing, London U.K.