Noninvasive and Continuous Monitoring of On-Chip Stem Cell Osteogenesis Using a Reusable Electrochemical Immunobiosensor

Noninvasive and Continuous Monitoring of On-Chip Stem Cell Osteogenesis Using a Reusable Electrochemical Immunobiosensor

Noninvasive monitoring of biofabricated tissues during the biomanufacturing process is needed to obtain reproducible, healthy, and functional tissues. Measuring the levels of biomarkers secreted from tissues is a promising strategy to understand the status of tissues during biofabrication. Continuou...

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Bibliographic Details
Published in:ACS sensors Vol. 9; no. 5; pp. 2334 - 2345
Main Authors: Rezaei, Zahra, Navarro Torres, Andrea, Ge, David, Wang, Ting, Méndez Terán, Eloísa Carolina, García Vera, Stefany Elizabeth, Bassous, Nicole Joy, Soria, Oscar Yael Perez, Ávila Ramírez, Alan Eduardo, Flores Campos, Luis Mario, Azuela Rosas, Diego Arnoldo, Hassan, Shabir, Khorsandi, Danial, Jucaud, Vadim, Hussain, Mohammad Asif, Khateeb, Abdulhameed, Zhang, Yu Shrike, Lee, HeaYeon, Kim, Deok-Ho, Khademhosseini, Ali, Dokmeci, Mehmet Remzi, Shin, Su Ryon
Format: Journal Article
Language:English
Published: United States American Chemical Society 24-05-2024
Subjects:
Biosensing Techniques - instrumentation
Biosensing Techniques - methods
Electrochemical Techniques - instrumentation
Electrochemical Techniques - methods
Humans
Immunoassay - instrumentation
Immunoassay - methods
Lab-On-A-Chip Devices
Mesenchymal Stem Cells - cytology
Osteogenesis
Osteopontin - analysis
Osteopontin - metabolism
reusable biosensor
electrochemical impedance spectroscopy
osteogenesis
bioreactor
human mesenchymal stem cells
osteopontin
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Summary:Noninvasive monitoring of biofabricated tissues during the biomanufacturing process is needed to obtain reproducible, healthy, and functional tissues. Measuring the levels of biomarkers secreted from tissues is a promising strategy to understand the status of tissues during biofabrication. Continuous and real-time information from cultivated tissues enables users to achieve scalable manufacturing. Label-free biosensors are promising candidates for detecting cell secretomes since they can be noninvasive and do not require labor-intensive processes such as cell lysing. Moreover, most conventional monitoring techniques are single-use, conducted at the end of the fabrication process, and, challengingly, are not permissive to in-line and continual detection. To address these challenges, we developed a noninvasive and continual monitoring platform to evaluate the status of cells during the biofabrication process, with a particular focus on monitoring the transient processes that stem cells go through during in vitro differentiation over extended periods. We designed and evaluated a reusable electrochemical immunosensor with the capacity for detecting trace amounts of secreted osteogenic markers, such as osteopontin (OPN). The sensor has a low limit of detection (LOD), high sensitivity, and outstanding selectivity in complex biological media. We used this OPN immunosensor to continuously monitor on-chip osteogenesis of human mesenchymal stem cells (hMSCs) cultured 2D and 3D hydrogel constructs inside a microfluidic bioreactor for more than a month and were able to observe changing levels of OPN secretion during culture. The proposed platform can potentially be adopted for monitoring a variety of biological applications and further developed into a fully automated system for applications in advanced cellular biomanufacturing.
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ISSN:2379-3694
2379-3694
DOI:10.1021/acssensors.3c02165