Cardiotoxicity Assessment through a Polymer-Based Cantilever Platform: An Integrated Electro-Mechanical Screening Approach.

Autor: Kanade PP; School of Mechanical Engineering, Chonnam National University, Gwangju, 61186, South Korea.; Advanced Medical Device Research Center for Cardiovascular Disease, Chonnam National University, Gwangju, 61186, Republic of Korea., Oyunbaatar NE; School of Mechanical Engineering, Chonnam National University, Gwangju, 61186, South Korea.; Advanced Medical Device Research Center for Cardiovascular Disease, Chonnam National University, Gwangju, 61186, Republic of Korea., Kim J; School of Mechanical Engineering, Chonnam National University, Gwangju, 61186, South Korea.; Advanced Medical Device Research Center for Cardiovascular Disease, Chonnam National University, Gwangju, 61186, Republic of Korea., Lee BK; School of Mechanical Engineering, Chonnam National University, Gwangju, 61186, South Korea., Kim ES; Department of Biological Sciences, Chonnam National University, Gwangju, 61186, Republic of Korea., Lee DW; School of Mechanical Engineering, Chonnam National University, Gwangju, 61186, South Korea.; Advanced Medical Device Research Center for Cardiovascular Disease, Chonnam National University, Gwangju, 61186, Republic of Korea.; Center for Next-Generation Sensor Research and Development, Chonnam National University, Gwangju, 61186, Republic of Korea.
Jazyk: angličtina
Zdroj: Small (Weinheim an der Bergstrasse, Germany) [Small] 2024 Aug; Vol. 20 (33), pp. e2311274. Date of Electronic Publication: 2024 Mar 21.
DOI: 10.1002/smll.202311274
Abstrakt: Preclinical drug screening for cardiac toxicity has traditionally relied on observing changes in cardiomyocytes' electrical activity, primarily through invasive patch clamp techniques or non-invasive microelectrode arrays (MEA). However, relying solely on field potential duration (FPD) measurements for electrophysiological assessment can miss the full spectrum of drug-induced toxicity, as different drugs affect cardiomyocytes through various mechanisms. A more comprehensive approach, combining field potential and contractility measurements, is essential for accurate toxicity profiling, particularly for drugs targeting contractile proteins without affecting electrophysiology. However, previously proposed platform has significant limitations in terms of simultaneous measurement. The novel platform addresses these issues, offering enhanced, non-invasive evaluation of drug-induced cardiotoxicity. It features eight cantilevers with patterned strain sensors and MEA, enabling real-time monitoring of both cardiomyocyte contraction force and field potential. This system can detect minimum cardiac contraction force of ≈2 µN and field potential signals with 50 µm MEA diameter, using the same cardiomyocytes in measurements of two parameters. Testing with six drugs of varied mechanisms of action, the platform successfully identifies these mechanisms and accurately assesses toxicity profiles, including drugs not inhibiting potassium channels. This innovative approach presents a comprehensive, non-invasive method for cardiac function assessment, poised to revolutionize preclinical cardiotoxicity screening.
(© 2024 Wiley‐VCH GmbH.)
Databáze: MEDLINE
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