Ell Maximilian, Bui Mai Thu, Kigili Seyda, Zeck Günther, Prado-López Sonia
Institute of Biomedical Electronics, Faculty of Electrical Engineering and Information Technology, TU Wien, Vienna, Austria.
Institute of Solid State Electronics, Faculty of Electrical Engineering and Information Technology, TU Wien, Vienna, Austria.
Front Bioeng Biotechnol. 2024 May 13;12:1385730. doi: 10.3389/fbioe.2024.1385730. eCollection 2024.
With cancer as one of the leading causes of death worldwide, there is a need for the development of accurate, cost-effective, easy-to-use, and fast drug-testing assays. While the NCI 60 cell-line screening as the gold standard is based on a colorimetric assay, monitoring cells electrically constitutes a label-free and non-invasive tool to assess the cytotoxic effects of a chemotherapeutic treatment on cancer cells. For decades, impedance-based cellular assays extensively investigated various cell characteristics affected by drug treatment but lack spatiotemporal resolution. With progress in microelectrode fabrication, high-density Complementary Metal Oxide Semiconductor (CMOS)-based microelectrode arrays (MEAs) with subcellular resolution and time-continuous recording capability emerged as a potent alternative. In this article, we present a new cell adhesion noise (CAN)-based electrical imaging technique to expand CMOS MEA cell-biology applications: CAN spectroscopy enables drug screening quantification with single-cell spatial resolution. The chemotherapeutic agent 5-Fluorouracil exerts a cytotoxic effect on colorectal cancer (CRC) cells hampering cell proliferation and lowering cell viability. For proof-of-concept, we found sufficient accuracy and reproducibility for CAN spectroscopy compared to a commercially available standard colorimetric biological assay. This label-free, non-invasive, and fast electrical imaging technique complements standardized cancer screening methods with significant advances over established impedance-based approaches.
癌症是全球主要死因之一,因此需要开发准确、经济高效、易于使用且快速的药物检测方法。虽然作为金标准的美国国立癌症研究所(NCI)60细胞系筛选基于比色法,但对细胞进行电学监测构成了一种无标记且非侵入性的工具,用于评估化疗对癌细胞的细胞毒性作用。几十年来,基于阻抗的细胞检测广泛研究了受药物治疗影响的各种细胞特征,但缺乏时空分辨率。随着微电极制造技术的进步,具有亚细胞分辨率和时间连续记录能力的基于互补金属氧化物半导体(CMOS)的高密度微电极阵列(MEA)成为一种有力的替代方案。在本文中,我们提出了一种基于新的细胞黏附噪声(CAN)的电成像技术,以扩展CMOS MEA在细胞生物学中的应用:CAN光谱能够以单细胞空间分辨率进行药物筛选定量。化疗药物5-氟尿嘧啶对结肠直肠癌(CRC)细胞具有细胞毒性作用,会阻碍细胞增殖并降低细胞活力。为了验证概念,与市售的标准比色生物检测相比,我们发现CAN光谱具有足够的准确性和可重复性。这种无标记、非侵入性且快速的电成像技术对标准化癌症筛查方法起到了补充作用,与已有的基于阻抗的方法相比有显著进步。