Electrical Impedance Spectroscopy for Microtissue Spheroid Analysis in Hanging-Drop NetworksClick to copy article linkArticle link copied!
Abstract
Electrical impedance spectroscopy (EIS) as a label-free and noninvasive analysis method receives growing attention for monitoring three-dimensional tissue constructs. In this Article, we present the integration of an EIS readout function into the hanging-drop network platform, which has been designed for culturing microtissue spheroids in perfused multitissue configurations. Two pairs of microelectrodes have been implemented directly in the support of the hanging drops by using a small glass inlay inserted in the microfluidic structure. The pair of bigger electrodes is sensitive to the drop size and allows for drop size control over time. The pair of smaller electrodes is capable of monitoring, on the one hand, the size of microtissue spheroids to follow, for example, the growth of cancer microtissues, and, on the other hand, the beating of cardiac microtissues in situ. The presented results demonstrate the feasibility of an EIS readout within the framework of multifunctional hanging-drop networks.
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- Sara Abasi, John R. Aggas, Guillermo G. Garayar-Leyva, Brandon K. Walther, Anthony Guiseppi-Elie. Bioelectrical Impedance Spectroscopy for Monitoring Mammalian Cells and Tissues under Different Frequency Domains: A Review. ACS Measurement Science Au 2022, 2
(6)
, 495-516. https://doi.org/10.1021/acsmeasuresciau.2c00033
- Charalampos Pitsalidis, Anna-Maria Pappa, Alexander J. Boys, Ying Fu, Chrysanthi-Maria Moysidou, Douglas van Niekerk, Janire Saez, Achilleas Savva, Donata Iandolo, Róisín M. Owens. Organic Bioelectronics for In Vitro Systems. Chemical Reviews 2022, 122
(4)
, 4700-4790. https://doi.org/10.1021/acs.chemrev.1c00539
- Stefanie Fuchs, Sofia Johansson, Anders Ø. Tjell, Gabriel Werr, Torsten Mayr, Maria Tenje. In-Line Analysis of Organ-on-Chip Systems with Sensors: Integration, Fabrication, Challenges, and Potential. ACS Biomaterials Science & Engineering 2021, 7
(7)
, 2926-2948. https://doi.org/10.1021/acsbiomaterials.0c01110
- Zuan-Tao Lin, Jianhua Gu, Huie Wang, Albon Wu, Jingying Sun, Shuo Chen, Yaxi Li, Yifei Kong, Mei X. Wu, Tianfu Wu. Thermosensitive and Conductive Hybrid Polymer for Real-Time Monitoring of Spheroid Growth and Drug Responses. ACS Sensors 2021, 6
(6)
, 2147-2157. https://doi.org/10.1021/acssensors.0c02266
- Julian Schütt, Diana Isabel Sandoval Bojorquez, Elisabetta Avitabile, Eduardo Sergio Oliveros Mata, Gleb Milyukov, Juliane Colditz, Lucia Gemma Delogu, Martina Rauner, Anja Feldmann, Stefanie Koristka, Jan Moritz Middeke, Katja Sockel, Jürgen Fassbender, Michael Bachmann, Martin Bornhäuser, Gianaurelio Cuniberti, Larysa Baraban. Nanocytometer for smart analysis of peripheral blood and acute myeloid leukemia: a pilot study. Nano Letters 2020, 20
(9)
, 6572-6581. https://doi.org/10.1021/acs.nanolett.0c02300
- Lei Dong, Paolo S. Ravaynia, Qing-An Huang, Andreas Hierlemann, Mario M. Modena. Parallelized Wireless Sensing System for Continuous Monitoring of Microtissue Spheroids. ACS Sensors 2020, 5
(7)
, 2036-2043. https://doi.org/10.1021/acssensors.0c00481
- Jia Liu, Yuhao Qiang, Ofelia Alvarez, E Du. Electrical Impedance Characterization of Erythrocyte Response to Cyclic Hypoxia in Sickle Cell Disease. ACS Sensors 2019, 4
(7)
, 1783-1790. https://doi.org/10.1021/acssensors.9b00263
- Ketki Chawla, Mario M. Modena, Paolo S. Ravaynia, Flavio C. Lombardo, Martin Leonhardt, Gordana Panic, Sebastian C. Bürgel, Jennifer Keiser, Andreas Hierlemann. Impedance-Based Microfluidic Assay for Automated Antischistosomal Drug Screening. ACS Sensors 2018, 3
(12)
, 2613-2620. https://doi.org/10.1021/acssensors.8b01027
- Mario M. Modena, Ketki Chawla, Patrick M. Misun, Andreas Hierlemann. Smart Cell Culture Systems: Integration of Sensors and Actuators into Microphysiological Systems. ACS Chemical Biology 2018, 13
(7)
, 1767-1784. https://doi.org/10.1021/acschembio.7b01029
- Dingkun Ren, Chi On Chui. Feasibility of Tracking Multiple Single-Cell Properties with Impedance Spectroscopy. ACS Sensors 2018, 3
(5)
, 1005-1015. https://doi.org/10.1021/acssensors.8b00152
- Lucas Armbrecht and Petra S. Dittrich . Recent Advances in the Analysis of Single Cells. Analytical Chemistry 2017, 89
(1)
, 2-21. https://doi.org/10.1021/acs.analchem.6b04255
- Ayda Pourmostafa, Anant Bhusal, Niranjan Haridas Menon, Zhenglong Li, Sagnik Basuray, Amir K. Miri. Integrating conductive electrodes into hydrogel-based microfluidic chips for real-time monitoring of cell response. Frontiers in Bioengineering and Biotechnology 2024, 12 https://doi.org/10.3389/fbioe.2024.1421592
- Dennis M. Nahon, Renée Moerkens, Hande Aydogmus, Bas Lendemeijer, Adriana Martínez-Silgado, Jeroen M. Stein, Milica Dostanić, Jean-Philippe Frimat, Cristina Gontan, Mees N. S. de Graaf, Michel Hu, Dhanesh G. Kasi, Lena S. Koch, Kieu T. T. Le, Sangho Lim, Heleen H. T. Middelkamp, Joram Mooiweer, Paul Motreuil-Ragot, Eva Niggl, Cayetano Pleguezuelos-Manzano, Jens Puschhof, Nele Revyn, José M. Rivera-Arbelaez, Jelle Slager, Laura M. Windt, Mariia Zakharova, Berend J. van Meer, Valeria V. Orlova, Femke M. S. de Vrij, Sebo Withoff, Massimo Mastrangeli, Andries D. van der Meer, Christine L. Mummery. Standardizing designed and emergent quantitative features in microphysiological systems. Nature Biomedical Engineering 2024, 8
(8)
, 941-962. https://doi.org/10.1038/s41551-024-01236-0
- João Ferreira Gil, Carla Sofia Moura, Vania Silverio, Gil Gonçalves, Hélder A. Santos. Cancer Models on Chip: Paving the Way to Large‐Scale Trial Applications. Advanced Materials 2023, 35
(35)
https://doi.org/10.1002/adma.202300692
- Tao Tang, Trisna Julian, Doudou Ma, Yang Yang, Ming Li, Yoichiroh Hosokawa, Yaxiaer Yalikun. A review on intelligent impedance cytometry systems: Development, applications and advances. Analytica Chimica Acta 2023, 1269 , 341424. https://doi.org/10.1016/j.aca.2023.341424
- Anna Grazia Monteduro, Silvia Rizzato, Giusi Caragnano, Adriana Trapani, Gianluigi Giannelli, Giuseppe Maruccio. Organs-on-chips technologies – A guide from disease models to opportunities for drug development. Biosensors and Bioelectronics 2023, 231 , 115271. https://doi.org/10.1016/j.bios.2023.115271
- Jonathan Sabaté del Río, Jooyoung Ro, Heejeong Yoon, Tae-Eun Park, Yoon-Kyoung Cho. Integrated technologies for continuous monitoring of organs-on-chips: Current challenges and potential solutions. Biosensors and Bioelectronics 2023, 224 , 115057. https://doi.org/10.1016/j.bios.2022.115057
- Nassim Rousset, Rubén López Sandoval, Mario Matteo Modena, Andreas Hierlemann, Patrick M. Misun. Modeling and measuring glucose diffusion and consumption by colorectal cancer spheroids in hanging drops using integrated biosensors. Microsystems & Nanoengineering 2022, 8
(1)
https://doi.org/10.1038/s41378-021-00348-w
- Shuge Liu, Ping Zhu, Yulan Tian, Yating Chen, Yage Liu, Wei Chen, Liping Du, Chunsheng Wu. Preparation and application of taste bud organoids in biomedicine towards chemical sensation mechanisms. Biotechnology and Bioengineering 2022, 119
(8)
, 2015-2030. https://doi.org/10.1002/bit.28109
- Lanjie Lei, Biao Ma, Chengtao Xu, Hong Liu. Emerging tumor-on-chips with electrochemical biosensors. TrAC Trends in Analytical Chemistry 2022, 153 , 116640. https://doi.org/10.1016/j.trac.2022.116640
- Dian Anggraini, Nobutoshi Ota, Yigang Shen, Tao Tang, Yo Tanaka, Yoichiroh Hosokawa, Ming Li, Yaxiaer Yalikun. Recent advances in microfluidic devices for single-cell cultivation: methods and applications. Lab on a Chip 2022, 22
(8)
, 1438-1468. https://doi.org/10.1039/D1LC01030A
- Franziska D. Zitzmann, Sabine Schmidt, Max Naumann, Detlev Belder, Heinz-Georg Jahnke, Andrea A. Robitzki. Multielectrode biosensor chip for spatial resolution screening of 3D cell models based on microcavity arrays. Biosensors and Bioelectronics 2022, 202 , 114010. https://doi.org/10.1016/j.bios.2022.114010
- Rituparna Addy, Ankit Yadav, Manoj Kumar, Ubhat Ali, Ankenapally Anjali, Vijay Kumar Garlapati, Sudipa Bhadra, Surajbhan Sevda. Bioelectrochemical methods in biomolecular analysis. 2022, 65-104. https://doi.org/10.1016/B978-0-323-85147-3.00011-6
- Sonia Youhanna, Aurino M. Kemas, Lena Preiss, Yitian Zhou, Joanne X. Shen, Selgin D. Cakal, Francesco S. Paqualini, Sravan K. Goparaju, Reza Zandi Shafagh, Johan Ulrik Lind, Carl M. Sellgren, Volker M. Lauschke, . Organotypic and Microphysiological Human Tissue Models for Drug Discovery and Development—Current State-of-the-Art and Future Perspectives. Pharmacological Reviews 2022, 74
(1)
, 141-206. https://doi.org/10.1124/pharmrev.120.000238
- Mostafa Azimzadeh, Patricia Khashayar, Meitham Amereh, Nishat Tasnim, Mina Hoorfar, Mohsen Akbari. Microfluidic-Based Oxygen (O2) Sensors for On-Chip Monitoring of Cell, Tissue and Organ Metabolism. Biosensors 2022, 12
(1)
, 6. https://doi.org/10.3390/bios12010006
- Zhen Zhu, Yangye Geng, Yingying Wang, Ke Liu, Zhenxiang Yi, Xiangwei Zhao, Shuiping Ouyang, Ke Zheng, Yimin Fan, Zixin Wang. Real-Time Monitoring of Dissection Events of Single Budding Yeast in a Microfluidic Cell-Culturing Device Integrated With Electrical Impedance Biosensor. Frontiers in Bioengineering and Biotechnology 2021, 9 https://doi.org/10.3389/fbioe.2021.783428
- Santa Bērziņa, Alexandra Harrison, Valérie Taly, Wenjin Xiao. Technological Advances in Tumor-On-Chip Technology: From Bench to Bedside. Cancers 2021, 13
(16)
, 4192. https://doi.org/10.3390/cancers13164192
- Lingyan Gong, Chayakorn Petchakup, Pujiang Shi, Pei Leng Tan, Lay Poh Tan, Chor Yong Tay, Han Wei Hou. Direct and Label‐Free Cell Status Monitoring of Spheroids and Microcarriers Using Microfluidic Impedance Cytometry. Small 2021, 17
(21)
https://doi.org/10.1002/smll.202007500
- Erika Ferrari, Cecilia Palma, Simone Vesentini, Paola Occhetta, Marco Rasponi. Integrating Biosensors in Organs-on-Chip Devices: A Perspective on Current Strategies to Monitor Microphysiological Systems. Biosensors 2020, 10
(9)
, 110. https://doi.org/10.3390/bios10090110
- Tatiana Gerasimenko, Sergey Nikulin, Galina Zakharova, Andrey Poloznikov, Vladimir Petrov, Ancha Baranova, Alexander Tonevitsky. Impedance Spectroscopy as a Tool for Monitoring Performance in 3D Models of Epithelial Tissues. Frontiers in Bioengineering and Biotechnology 2020, 7 https://doi.org/10.3389/fbioe.2019.00474
- Felix Kurth, Erika Györvary, Sarah Heub, Diane Ledroit, Samantha Paoletti, Kasper Renggli, Vincent Revol, Marine Verhulsel, Gilles Weder, Frédéric Loizeau. Organs-on-a-chip engineering. 2020, 47-130. https://doi.org/10.1016/B978-0-12-817202-5.00003-6
- Kasper Renggli, Olivier Frey. Design and engineering of multiorgan systems. 2020, 393-427. https://doi.org/10.1016/B978-0-12-817202-5.00012-7
- Arthur Luiz Alves de Araujo, Julien Claudel, Djilali Kourtiche, Mustapha Nadi. Use of an Insulation Layer on the Connection Tracks of a Biosensor with Coplanar Electrodes to Increase the Normalized Impedance Variation. Biosensors 2019, 9
(3)
, 108. https://doi.org/10.3390/bios9030108
- Kaoru Hiramoto, Kosuke Ino, Yuji Nashimoto, Kentaro Ito, Hitoshi Shiku. Electric and Electrochemical Microfluidic Devices for Cell Analysis. Frontiers in Chemistry 2019, 7 https://doi.org/10.3389/fchem.2019.00396
- Heinz-Georg Jahnke, Sabine Schmidt, Ronny Frank, Winnie Weigel, Christoph Prönnecke, Andrea A. Robitzki. FEM-based design of optical transparent indium tin oxide multielectrode arrays for multiparametric, high sensitive cell based assays. Biosensors and Bioelectronics 2019, 129 , 208-215. https://doi.org/10.1016/j.bios.2018.09.095
- Mario Rothbauer, Julie M Rosser, Helene Zirath, Peter Ertl. Tomorrow today: organ-on-a-chip advances towards clinically relevant pharmaceutical and medical in vitro models. Current Opinion in Biotechnology 2019, 55 , 81-86. https://doi.org/10.1016/j.copbio.2018.08.009
- Longjun Gu, Jinghan Feng, Donghui Zhang, Pu Chen. Bioengineering 3D Cardiac Microtissues Using Bioassembly. 2019, 107-123. https://doi.org/10.1007/978-3-030-20047-3_6
- Raziyeh Bounik, Massimiliano Gusmaroli, Patrick M. Misun, Vijay Viswam, Andreas Hierlemann, Mario M. Modena. Integration of Discrete Sensors and Microelectrode Arrays Into Open Microfluidic Hanging-Drop Networks. 2019, 441-444. https://doi.org/10.1109/MEMSYS.2019.8870732
- M. Amini, J. Hisdal, H. Kalvøy. Applications of bioimpedance measurement techniques in tissue engineering. Journal of Electrical Bioimpedance 2018, 9
(1)
, 142-158. https://doi.org/10.2478/joeb-2018-0019
- Zhen Zhu, Weijie Chen, Beitong Tian, Yulong Luo, Jianfeng Lan, Di Wu, Di Chen, Zixin Wang, Dejing Pan. Using microfluidic impedance cytometry to measure C. elegans worms and identify their developmental stages. Sensors and Actuators B: Chemical 2018, 275 , 470-482. https://doi.org/10.1016/j.snb.2018.07.169
- Khashayar Moshksayan, Navid Kashaninejad, Mohammad Said Saidi. Inventions and Innovations in Preclinical Platforms for Cancer Research. Inventions 2018, 3
(3)
, 43. https://doi.org/10.3390/inventions3030043
- Elise A. Aeby, Patrick M. Misun, Andreas Hierlemann, Olivier Frey. Microfluidic Hydrogel Hanging‐Drop Network for Long‐Term Culturing of 3D Microtissues and Simultaneous High‐Resolution Imaging. Advanced Biosystems 2018, 2
(7)
https://doi.org/10.1002/adbi.201800054
- Khashayar Moshksayan, Navid Kashaninejad, Majid Ebrahimi Warkiani, John G. Lock, Hajar Moghadas, Bahar Firoozabadi, Mohammad Said Saidi, Nam-Trung Nguyen. Spheroids-on-a-chip: Recent advances and design considerations in microfluidic platforms for spheroid formation and culture. Sensors and Actuators B: Chemical 2018, 263 , 151-176. https://doi.org/10.1016/j.snb.2018.01.223
- Frank Alexander, Sebastian Eggert, Joachim Wiest. A novel lab-on-a-chip platform for spheroid metabolism monitoring. Cytotechnology 2018, 70
(1)
, 375-386. https://doi.org/10.1007/s10616-017-0152-x
- Jong Seok Park, Moez Karim Aziz, Sensen Li, Taiyun Chi, Sandra Ivonne Grijalva, Jung Hoon Sung, Hee Cheol Cho, Hua Wang. 1024-Pixel CMOS Multimodality Joint Cellular Sensor/Stimulator Array for Real-Time Holistic Cellular Characterization and Cell-Based Drug Screening. IEEE Transactions on Biomedical Circuits and Systems 2018, 12
(1)
, 80-94. https://doi.org/10.1109/TBCAS.2017.2759220
- Patrick M. Misun, Axel K. Birchler, Moritz Lang, Andreas Hierlemann, Olivier Frey. Fabrication and Operation of Microfluidic Hanging-Drop Networks. 2018, 183-202. https://doi.org/10.1007/978-1-4939-7792-5_15
- Mario Rothbauer, Helene Zirath, Peter Ertl. Recent advances in microfluidic technologies for cell-to-cell interaction studies. Lab on a Chip 2018, 18
(2)
, 249-270. https://doi.org/10.1039/C7LC00815E
- Jochen Kieninger, Andreas Weltin, Hubert Flamm, Gerald A. Urban. Microsensor systems for cell metabolism – from 2D culture to organ-on-chip. Lab on a Chip 2018, 18
(9)
, 1274-1291. https://doi.org/10.1039/C7LC00942A
- Hancong Wu, Yunjie Yang, Pierre O. Bagnaninchi, Jiabin Jia. Electrical impedance tomography for real-time and label-free cellular viability assays of 3D tumour spheroids. The Analyst 2018, 143
(17)
, 4189-4198. https://doi.org/10.1039/C8AN00729B
- V. F. Curto, M. P. Ferro, F. Mariani, E. Scavetta, R. M. Owens. A planar impedance sensor for 3D spheroids. Lab on a Chip 2018, 18
(6)
, 933-943. https://doi.org/10.1039/C8LC00067K
- Jong Seok Park, Sandra I. Grijalva, Moez K. Aziz, Taiyun Chi, Sensen Li, Michael N. Sayegh, Adam Wang, Hee Cheol Cho, Hua Wang. Multi-parametric cell profiling with a CMOS quad-modality cellular interfacing array for label-free fully automated drug screening. Lab on a Chip 2018, 18
(19)
, 3037-3050. https://doi.org/10.1039/C8LC00156A
- Kosuke Ino, Hitoshi Shiku, Tomokazu Matsue. Bioelectrochemical applications of microelectrode arrays in cell analysis and engineering. Current Opinion in Electrochemistry 2017, 5
(1)
, 146-151. https://doi.org/10.1016/j.coelec.2017.08.004
- Kosuke Ino, Mustafa Şen, Hitoshi Shiku, Tomokazu Matsue. Micro/nanoelectrochemical probe and chip devices for evaluation of three-dimensional cultured cells. The Analyst 2017, 142
(23)
, 4343-4354. https://doi.org/10.1039/C7AN01442B
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