Serioli Laura, Gruzinskyte Lina, Zappalà Giulia, Hwu En Te, Laksafoss Trygvi Zachariassen, Jensen Peter Lunding, Demarchi Danilo, Müllertz Anette, Boisen Anja, Zór Kinga
The Danish National Research Foundation and Villum Foundation's Center for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics (IDUN), Department of Health Technology, Technical University of Denmark, Denmark.
BioInnovation Institute Foundation, Copenhagen N 2800, Denmark.
Lab Chip. 2023 Mar 14;23(6):1603-1612. doi: 10.1039/d2lc00984f.
, cell-based assays are essential in diagnostics and drug development. There are ongoing efforts to establish new technologies that enable real-time detection of cell-drug interaction during culture under flow conditions. Our compact (10 × 10 × 8.5 cm) cell culture and microscope on disc (CMoD) platform aims to decrease the application barriers of existing lab-on-a-chip (LoC) approaches. For the first time in a centrifugal device, (i) cells were cultured for up to six days while a spindle motor facilitated culture medium perfusion, and (ii) an onboard microscope enabled live bright-field imaging of cells while the data wirelessly transmitted to a computer. The quantification of cells from the acquired images was done using artificial intelligence (AI) software. After optimization, the obtained cell viability data from the AI-based image analysis proved to correlate well with data collected from commonly used image analysis software. The CMoD was also suitable for conducting a proof-of-concept toxicity assay with HeLa cells under continuous flow. The half-maximal inhibitory time (IT50) for various concentrations of doxorubicin (DOX) in the case of HeLa cells in flow, was shown to be lower than the IT50 obtained from a static cytotoxicity assay, indicating a faster onset of cell death in flow. The CMoD proved to be easy to handle, enabled cell culture and monitoring without assistance, and is a promising tool for examining the dynamic processes of cells in real-time assays.
基于细胞的检测在诊断和药物开发中至关重要。目前正在努力建立新技术，以实现对流动条件下培养过程中细胞与药物相互作用的实时检测。我们紧凑的（10×10×8.5厘米）盘上细胞培养和显微镜（CMoD）平台旨在降低现有芯片实验室（LoC）方法的应用障碍。在离心装置中首次实现了：（i）细胞培养长达六天，同时由一个纺锤形电机促进培养基灌注；（ii）一个机载显微镜能够对细胞进行实时明场成像，同时数据无线传输到计算机。使用人工智能（AI）软件对采集图像中的细胞进行定量分析。经过优化，基于AI的图像分析获得的细胞活力数据与常用图像分析软件收集的数据显示出良好的相关性。CMoD还适用于在连续流动条件下对HeLa细胞进行概念验证毒性试验。在流动条件下，HeLa细胞对不同浓度阿霉素（DOX）的半数最大抑制时间（IT50）低于静态细胞毒性试验获得的IT50，表明流动条件下细胞死亡的起始更快。CMoD被证明易于操作，无需辅助即可进行细胞培养和监测，是实时检测中用于检查细胞动态过程的有前途的工具。
