Aptamer-Based Microfluidic Electrochemical Biosensor for Monitoring Cell-Secreted Trace Cardiac Biomarkers.
Continual monitoring of secreted biomarkers from organ-on-a-chip models is desired to understand their responses to drug exposure in a noninvasive manner. To achieve this goal, analytical methods capable of monitoring trace amounts of secreted biomarkers are of particular interest. However, a majority of existing biosensing techniques suffer from limited sensitivity, selectivity, stability, and require large working volumes, especially when cell culture medium is involved, which usually contains a plethora of nonspecific binding proteins and interfering compounds. Hence, novel analytical platforms are needed to provide noninvasive, accurate information on the status of organoids at low working volumes. Here, we report a novel microfluidic aptamer-based electrochemical biosensing platform for monitoring damage to cardiac organoids. The system is scalable, low-cost, and compatible with microfluidic platforms easing its integration with microfluidic bioreactors. To create the creatine kinase (CK)-MB biosensor, the microelectrode was functionalized with aptamers that are specific to CK-MB biomarker secreted from a damaged cardiac tissue. Compared to antibody-based sensors, the proposed aptamer-based system was highly sensitive, selective, and stable. The performance of the sensors was assessed using a heart-on-a-chip system constructed from human embryonic stem cell-derived cardiomyocytes following exposure to a cardiotoxic drug, doxorubicin. The aptamer-based biosensor was capable of measuring trace amounts of CK-MB secreted by the cardiac organoids upon drug treatments in a dose-dependent manner, which was in agreement with the beating behavior and cell viability analyses. We believe that, our microfluidic electrochemical biosensor using aptamer-based capture mechanism will find widespread applications in integration with organ-on-a-chip platforms for in situ detection of biomarkers at low abundance and high sensitivity.
Biomaterials Innovation Research Center, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts 02139, United States.|Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.|Wyss Institute for Biologically Inspired Engineering, Harvard University , Boston, Massachusetts 02115, United States.
Su Ryon
SR
Shin
Biomaterials Innovation Research Center, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts 02139, United States.|Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.|Wyss Institute for Biologically Inspired Engineering, Harvard University , Boston, Massachusetts 02115, United States.
Yu Shrike
YS
Zhang
Biomaterials Innovation Research Center, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts 02139, United States.|Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
Duck-Jin
DJ
Kim
Biomaterials Innovation Research Center, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts 02139, United States.|Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.|Chemistry & Chemical Engineering Research Center of Iran , P.O. Box 14334-186, Tehran, Iran.
Ahmad
A
Manbohi
Biomaterials Innovation Research Center, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts 02139, United States.|Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.|Eskisehir Osmangazi University , Faculty of Engineering and Architecture, Metallurgical and Materials Engineering Department, 26480 Eskisehir, Turkey.
Huseyin
H
Avci
Biomaterials Innovation Research Center, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts 02139, United States.|Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.|Politecnico di Torino , Department of Electronics and Telecommunications (DET), Corso Duca degli Abruzzi 24, 10129, Torino, Italy.
Antonia
A
Silvestri
Biomaterials Innovation Research Center, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts 02139, United States.|Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
Julio
J
Aleman
Biomaterials Innovation Research Center, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts 02139, United States.|Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.|Biosensor National Special Laboratory, Key Laboratory of Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, Zhejiang University , Hangzhou, Zhejiang 310027, PR China.
Ning
N
Hu
Biomaterials Innovation Research Center, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts 02139, United States.|Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.|Izmir Katip Celebi University , Faculty of Engineering and Architecture, Department of Biomedical Engineering, 35620 Izmir, Turkey.
Tugba
T
Kilic
Dr. Li Dak-Sum Research Centre, The University of Hong Kong - Karolinska Institutet Collaboration in Regenerative Medicine, The University of Hong Kong , Hong Kong.|Ming Wai Lau Centre for Reparative Medicine , Karolinska Institutet, SE-171 77, Stockholm, Sweden.
Wendy
W
Keung
Biomaterials Innovation Research Center, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts 02139, United States.|Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.|The BioRobotics Institute, Scuola Superiore Sant'Anna , Viale Rinaldo Piaggio 34, 56025 Pontedera, Pisa, Italy.
Martina
M
Righi
Biomaterials Innovation Research Center, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts 02139, United States.|Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
Pribpandao
P
Assawes
Faculty of Applied Medical Sciences, Department of Medical Technology, King Abdulaziz University , Jeddah, 21589, Saudi Arabia.|Center of Innovation in Personalized Medicine, King Fahd Medical Research Center, King Abdulaziz University , Jeddah, 21589, Saudi Arabia.
Hani A
HA
Alhadrami
Dr. Li Dak-Sum Research Centre, The University of Hong Kong - Karolinska Institutet Collaboration in Regenerative Medicine, The University of Hong Kong , Hong Kong.|Ming Wai Lau Centre for Reparative Medicine , Karolinska Institutet, SE-171 77, Stockholm, Sweden.
Ronald A
RA
Li
Biomaterials Innovation Research Center, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts 02139, United States.|Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.|Wyss Institute for Biologically Inspired Engineering, Harvard University , Boston, Massachusetts 02115, United States.
Mehmet R
MR
Dokmeci
Biomaterials Innovation Research Center, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts 02139, United States.|Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.|Wyss Institute for Biologically Inspired Engineering, Harvard University , Boston, Massachusetts 02115, United States.|Department of Physics, King Abdulaziz University , Jeddah 21569, Saudi Arabia.|College of Animal Bioscience and Technology, Department of Bioindustrial Technologies, Konkuk University , Hwayang-dong, Kwangjin-gu, Seoul, Republic of Korea.
Ali
A
Khademhosseini