title: Drug-induced cellular death dynamics monitored by a highly sensitive organic electrochemical system.
abstract: We propose and demonstrate a sensitive diagnostic device based on an Organic Electrochemical Transistor (OECT) for direct in-vitro monitoring cell death. The system efficiently monitors cell death dynamics, being able to detect signals related to specific death mechanisms, namely necrosis or early/late apoptosis, demonstrating a reproducible correlation between the OECT electrical response and the trends of standard cell death assays. The innovative design of the Twell-OECT system has been modeled to better correlate electrical signals with cell death dynamics. To qualify the device, we used a human lung adenocarcinoma cell line (A549) that was cultivated on the micro-porous membrane of a Transwell (Twell) support, and exposed to the anticancer drug doxorubicin. Time-dependent and dose-dependent dynamics of A549 cells exposed to doxorubicin are evaluated by monitoring cell death upon exposure to a range of doses and times that fully covers the protocols used in cancer treatment. The demonstrated ability to directly monitor cell stress and death dynamics upon drug exposure using simple electronic devices and, possibly, achieving selectivity to different cell dynamics is of great interest for several application fields, including toxicology, pharmacology, and therapeutics.
authors: Institute of Materials for Electronics and Magnetism, National Research Council, Parco Area delle Scienze 37/A, Parma 43124, Italy.
authors: Agostino
authors: A
authors: Romeo
authors: Institute of Materials for Electronics and Magnetism, National Research Council, Parco Area delle Scienze 37/A, Parma 43124, Italy.
authors: Giuseppe
authors: G
authors: Tarabella
authors: Institute of Materials for Electronics and Magnetism, National Research Council, Parco Area delle Scienze 37/A, Parma 43124, Italy. Electronic address: pasquale.dangelo@imem.cnr.it.
authors: Pasquale
authors: P
authors: D'Angelo
authors: Unit of Experimental Oncology, Department of Clinical and Experimental Medicine, University of Parma, Parma 43125, Italy.
authors: Cristina
authors: C
authors: Caffarra
authors: Unit of Experimental Oncology, Department of Clinical and Experimental Medicine, University of Parma, Parma 43125, Italy.
authors: Daniele
authors: D
authors: Cretella
authors: Unit of Experimental Oncology, Department of Clinical and Experimental Medicine, University of Parma, Parma 43125, Italy.
authors: Roberta
authors: R
authors: Alfieri
authors: Unit of Experimental Oncology, Department of Clinical and Experimental Medicine, University of Parma, Parma 43125, Italy.
authors: Pier Giorgio
authors: PG
authors: Petronini
authors: Institute of Materials for Electronics and Magnetism, National Research Council, Parco Area delle Scienze 37/A, Parma 43124, Italy. Electronic address: iannotta@imem.cnr.it.
authors: Salvatore
authors: S
authors: Iannotta
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis; D000077192:Adenocarcinoma of Lung; D017209:Apoptosis; D015374:Biosensing Techniques; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D055664:Electrochemical Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis
chemical_list: D004317:Doxorubicin
keywords: Apoptosis/necrosis; Biosensing; Cell death dynamics; Organic Electrochemical Transistor; Pharmacokinetics