Label‐Free and Regenerative Electrochemical Microfluidic Biosensors for Continual Monitoring of Cell Secretomes

Advanced Science - Tập 4 Số 5 - 2017
Su Ryon Shin1,2, Tuğba Kiliç1,2,3, Yu Shrike Zhang1,2, Hüseyin Avcı1,4,2, Ning Hu1,5,2, Duck Jin Kim1,2, Cristina Branco1,2,6, Julio Aleman1,2, Solange Massa1,2,7, Antonia Silvestri1,2,6, Jian Kang1,2,6, Anna Desalvo1,2, Mohammed Abdullah Hussaini8, Sukyoung Chae1,2, Alessandro Polini1,2, Karl Wahlin1,2, Mohammad Asif Hussain8, JuKyung Lee9, Mehmet R. Dokmeci1,2, Ali Khademhosseini1,10,11,2
1Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02139, USA
2Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
3Izmir Katip Celebi University, Faculty of Engineering and Architecture, Department of Biomedical Engineering, 35620 Izmir, Turkey
4Department of Metallurgical and Materials Engineering, Faculty of Engineering and Architecture, Eskisehir Osmangazi University, 26040 Eskisehir, Turkey
5Biosensor National Special Laboratory, Key Laboratory of Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027 P. R. China
6Politecnico di Torino, Department of Electronics and Telecommunications (DET), Corso Duca degli Abruzzi 24, 10129 Torino, Italy
7Programa de Doctorado en Biomedicina, Universidad de los Andes, Santiago, 7620001 Chile
8Department of Electrical and Computer Engineering, King Abdulaziz University, Jeddah 21589, Saudi Arabia
9Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115 USA
10Department of Bioindustrial Technologies, College of Animal Bioscience and Technology, Konkuk University, Hwayang-dong, Kwangjin-gu, Seoul, 05029 Republic of Korea
11Department of Physics, King Abdulaziz University, Jeddah 21569, Saudi Arabia

Tóm tắt

Development of an efficient sensing platform capable of continual monitoring of biomarkers is needed to assess the functionality of the in vitro organoids and to evaluate their biological responses toward pharmaceutical compounds or chemical species over extended periods of time. Here, a novel label‐free microfluidic electrochemical (EC) biosensor with a unique built‐in on‐chip regeneration capability for continual measurement of cell‐secreted soluble biomarkers from an organoid culture in a fully automated manner without attenuating the sensor sensitivity is reported. The microfluidic EC biosensors are integrated with a human liver‐on‐a‐chip platform for continual monitoring of the metabolic activity of the organoids by measuring the levels of secreted biomarkers for up to 7 d, where the metabolic activity of the organoids is altered by a systemically applied drug. The variations in the biomarker levels are successfully measured by the microfluidic regenerative EC biosensors and agree well with cellular viability and enzyme‐linked immunosorbent assay analyses, validating the accuracy of the unique sensing platform. It is believed that this versatile and robust microfluidic EC biosensor that is capable of automated and continual detection of soluble biomarkers will find widespread use for long‐term monitoring of human organoids during drug toxicity studies or efficacy assessments of in vitro platforms.

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