Pauwelyn Thomas, Stahl Richard, Mayo Lakyn, Zheng Xuan, Lambrechts Andy, Janssens Stefan, Lagae Liesbet, Reumers Veerle, Braeken Dries
Department of Physics and Astronomy, KU Leuven, Celestijnenlaan 200D, 3001 Leuven, Belgium.
imec, Kapeldreef 75, 3001 Leuven, Belgium.
Biomed Opt Express. 2018 Mar 22;9(4):1827-1841. doi: 10.1364/BOE.9.001827. eCollection 2018 Apr 1.
The high rate of drug attrition caused by cardiotoxicity is a major challenge for drug development. Here, we developed a reflective lens-free imaging (RLFI) approach to non-invasively record cell deformation in cardiac monolayers with high temporal (169 fps) and non-reconstructed spatial resolution (352 µm) over a field-of-view of maximally 57 mm. The method is compatible with opaque surfaces and silicon-based devices. Further, we demonstrated that the system can detect the impairment of both contractility and fast excitation waves in cardiac monolayers. Additionally, the RLFI device was implemented on a CMOS-based microelectrode array to retrieve multi-parametric information of cardiac cells, thereby offering more in-depth analysis of drug-induced (cardiomyopathic) effects for preclinical cardiotoxicity screening applications.
心脏毒性导致的高药物淘汰率是药物研发面临的一项重大挑战。在此，我们开发了一种无透镜反射成像（RLFI）方法，以高时间分辨率（169帧/秒）和非重建空间分辨率（352 µm）在最大57 mm的视野范围内无创记录心脏单层细胞的变形。该方法与不透明表面和硅基器件兼容。此外，我们证明该系统能够检测心脏单层细胞收缩性和快速兴奋波的损伤。此外，RLFI设备被应用于基于CMOS的微电极阵列上，以获取心脏细胞的多参数信息，从而为临床前心脏毒性筛查应用提供对药物诱导（心肌病）效应更深入的分析。
