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[PNAS]Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring


Organ-on-a-chip systems are miniaturized microfluidic 3D human tissue and organ models designed to recapitulate the important biological and physiological parameters of their in vivo counterparts. They have recently emerged as a viable platform for personalized medicine and drug screening. These in vitro models, featuring biomimetic compositions, architectures, and functions, are expected to replace the conventional planar, static cell cultures and bridge the gap between the currently used preclinical animal models and the human body. Multiple organoid models may be further connected together through the microfluidics in a similar manner in which they are arranged in vivo, providing the capability to analyze multiorgan interactions. Although a wide variety of human organ-on-a-chip models have been created, there are limited efforts on the integration of multisensor systems. However, in situ continual measuring is critical in precise assessment of the microenvironment parameters and the dynamic responses of the organs to pharmaceutical compounds over extended periods of time. In addition, automated and noninvasive capability is strongly desired for long-term monitoring. Here, we report a fully integrated modular physical, biochemical, and optical sensing platform through a fluidics-routing breadboard, which operates organ-on-a-chip units in a continual, dynamic, and automated manner. We believe that this platform technology has paved a potential avenue to promote the performance of current organ-on-a-chip models in drug screening by integrating a multitude of real-time sensors to achieve automated in situ monitoring of biophysical and biochemical parameters.

Zhang YS1,2,3, Aleman J4,2,5, Shin SR4,2,3, Kilic T4,2,6, Kim D4,2, Mousavi Shaegh SA4,2,7, Massa S4,2,8, Riahi R4,2, Chae S4,2, Hu N4,2,9, Avci H4,2,10, Zhang W4,2,11, Silvestri A4,2,12, Sanati Nezhad A4,2,13, Manbohi A4,2,14, De Ferrari F4,2,12, Polini A4,2, Calzone G4,2, Shaikh N4,2,15, Alerasool P4,2, Budina E4,2, Kang J4,2, Bhise N4,2, Ribas J4,2,16, Pourmand A4,2,17, Skardal A5, Shupe T5, Bishop CE5, Dokmeci MR4,2,3, Atala A5, Khademhosseini A1,2,3,18,19.

1 Biomaterials Innovation Research Center, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139; alik@bwh.harvard.edu yszhang@research.bwh.harvard.edu.

2 Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, MA 02139.

3 Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115.

4 Biomaterials Innovation Research Center, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139.

5 Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157.

6 Department of Biomedical Engineering, Faculty of Engineering and Architecture, Izmir Katip Celebi University, Izmir 35620, Turkey.

7 Orthopaedic Research Center, Mashhad University of Medical Sciences, Mashhad 9176699199, Iran.

8 Graduate School Program in Biomedicine, Universidad de los Andes, Santiago 7620001, Chile.

9 Biosensor National Special Laboratory, Key Laboratory of Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, People's Republic of China.

10 Metallurgical and Materials Engineering Department, Faculty of Engineering and Architecture, Eskisehir Osmangazi University, Eskisehir 26030, Turkey.

11 Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, People's Republic of China.

12 Department of Electronics and Telecommunications, Polytechnic University of Turin, Turin 10129, Italy.

13 BioMEMS and Bioinspired Microfluidics Laboratory, Center for Bioengineering Research and Education, Department of Mechanical and Manufacturing Engineering, University of Calgary, Calgary, AB T2N 1N4, Canada.

14 Department of Marine Science, Iranian National Institute for Oceanography and Atmospheric Science, Tehran 1411813389, Iran.

15 Division of Engineering Science, Faculty of Applied Science and Engineering, University of Toronto, Toronto, ON, Canada M5S 1A4.

16 Doctoral Program in Experimental Biology and Biomedicine, Center for Neuroscience and Cell Biology, Institute for Interdisciplinary Research, University of Coimbra, Coimbra 3030-789, Portugal.

17 Department of Electrical Engineering, Sahand University of Technology, Tabriz 5331711111, Iran.

18 Department of Bioindustrial Technologies, College of Animal Bioscience and Technology, Konkuk University, Seoul 143-701, Republic of Korea.

19 Center for Nanotechnology, King Abdulaziz University, Jeddah 21569, Saudi Arabia.

Proc Natl Acad Sci U S A. 2017 Mar 6. pii: 201612906. doi: 10.1073/pnas.1612906114. [Epub ahead of print]

Link: http://www.pnas.org/content/early/2017/03/02/1612906114.long

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