TY - JOUR
T1 - Noninvasive and Continuous Monitoring of On-Chip Stem Cell Osteogenesis Using a Reusable Electrochemical Immunobiosensor
AU - Rezaei, Zahra
AU - Navarro Torres, Andrea
AU - Ge, David
AU - Wang, Ting
AU - Méndez Terán, Eloísa Carolina
AU - García Vera, Stefany Elizabeth
AU - Bassous, Nicole Joy
AU - Soria, Oscar Yael Perez
AU - Ávila Ramírez, Alan Eduardo
AU - Flores Campos, Luis Mario
AU - Azuela Rosas, Diego Arnoldo
AU - Hassan, Shabir
AU - Khorsandi, Danial
AU - Jucaud, Vadim
AU - Hussain, Mohammad Asif
AU - Khateeb, Abdulhameed
AU - Zhang, Yu Shrike
AU - Lee, Hea Yeon
AU - Kim, Deok Ho
AU - Khademhosseini, Ali
AU - Dokmeci, Mehmet Remzi
AU - Shin, Su Ryon
N1 - Publisher Copyright:
© 2024 American Chemical Society
PY - 2024/5/24
Y1 - 2024/5/24
N2 - 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.
AB - 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.
KW - bioreactor
KW - electrochemical impedance spectroscopy
KW - human mesenchymal stem cells
KW - osteogenesis
KW - osteopontin
KW - reusable biosensor
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UR - http://www.scopus.com/inward/citedby.url?scp=85191173362&partnerID=8YFLogxK
U2 - 10.1021/acssensors.3c02165
DO - 10.1021/acssensors.3c02165
M3 - Article
C2 - 38639453
AN - SCOPUS:85191173362
SN - 2379-3694
VL - 9
SP - 2334
EP - 2345
JO - ACS sensors
JF - ACS sensors
IS - 5
ER -