Mechanobiology Institute and Department of Biological Sciences, National University of Singapore, Singapore, Singapore.
Institute of Molecular Oncology, Italian Foundation for Cancer Research, Milan, Italy.
PLoS One. 2019 Jul 17;14(7):e0218757. doi: 10.1371/journal.pone.0218757. eCollection 2019.
Current cancer diagnosis involves the use of nuclear morphology and chromatin condensation signatures for accurate advanced stage classification. While such diagnostic approaches rely on high resolution imaging of the cell nucleus using expensive microscopy systems, developing portable mobile microscopes to visualize nuclear and chromatin condensation patterns is desirable at clinical settings with limited infrastructure. In this study, we develop a portable fluorescent mobile microscope capable of acquiring high resolution images of the nucleus and chromatin. Using this we extracted nuclear morphometric and chromatin texture based features and were able to discriminate between normal and cancer cells with similar accuracy as wide-field fluorescence microscopy. We were also able to detect subtle changes in nuclear and chromatin features in cells subjected to compressive forces, cytoskeletal perturbations and cytokine stimulation, thereby highlighting the sensitivity of the portable microscope. Taken together, we present a versatile platform to exploit nuclear morphometrics and chromatin condensation features as physical biomarkers for point-of-care diagnostic solutions.
目前的癌症诊断涉及使用核形态和染色质凝聚特征进行准确的晚期分类。虽然这些诊断方法依赖于使用昂贵的显微镜系统对细胞核进行高分辨率成像，但在基础设施有限的临床环境中，开发便携式移动显微镜来可视化核和染色质凝聚模式是很有必要的。在这项研究中，我们开发了一种便携式荧光显微镜，能够获取细胞核和染色质的高分辨率图像。使用该显微镜，我们提取了基于核形态计量学和染色质纹理的特征，并能够以与宽场荧光显微镜相似的准确度区分正常细胞和癌细胞。我们还能够检测到受到压缩力、细胞骨架扰动和细胞因子刺激的细胞中核和染色质特征的细微变化，从而突出了便携式显微镜的灵敏度。总之，我们提出了一个通用平台，利用核形态计量学和染色质凝聚特征作为即时诊断解决方案的物理生物标志物。
