State Key Laboratory of Analytical Chemistry for Life Science and School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.
The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School and Clinical Cancer Institute of Nanjing University, Nanjing 210008, China.
ACS Appl Mater Interfaces. 2024 Jun 26;16(25):32078-32086. doi: 10.1021/acsami.4c05735. Epub 2024 Jun 12.
The traditional recognition of extracellular matrix (ECM) at tissue sections relies on the time-consuming immunofluorescence that could not meet the demand of rapid diagnosis. Herein, we introduce a thickness-resolved electrochemiluminescence (ECL) microscopy to image thin-layer ECM at tissue sections for fast histopathological analysis. The unique surface-confined ECL mechanism enables to unveil the diversity and complexity of multiple tissue structures with varying thicknesses. Notably, the short lifetimes and the limited diffusion of electrogenerated coreactant radicals combined with their chemical reactivity result in a 2-fold increase in ECL intensity on ECM structures compared to the remaining tissue, enabling ECM visualization without specific labeling. The further quantitation of the ECM localization within tissue sections furnishes crucial insights into tumor progression and, more importantly, differentiates carcinoma and paracancerous tissues from patients in less than 30 min. Moreover, the reported electrochemistry-based microscopy is a dynamic approach allowing to investigate the transport, tortuosity, and trafficking properties through the tissues. This thickness-resolved recognition strategy not only opens new avenues for imaging complex samples but also holds promise for expediting tissue pathologic diagnosis, offering a more automated protocol with enhanced quantitative data compared to current intraoperative pathology methods.
传统上，通过耗时的免疫荧光法来识别组织切片中的细胞外基质 (ECM)，但这种方法无法满足快速诊断的需求。在此，我们引入了一种厚度分辨的电化学发光 (ECL) 显微镜，用于对组织切片中的薄层 ECM 进行成像，以进行快速的组织病理学分析。独特的表面限制 ECL 机制能够揭示具有不同厚度的多种组织结构的多样性和复杂性。值得注意的是，电生成的反应物自由基的短寿命和有限扩散及其化学反应性导致 ECM 结构上的 ECL 强度增加了 2 倍，与剩余组织相比，无需特定标记即可实现 ECM 可视化。对组织切片中 ECM 定位的进一步定量分析为肿瘤进展提供了重要的见解，更重要的是，能够在不到 30 分钟的时间内区分癌组织和癌旁组织。此外，所报道的基于电化学的显微镜是一种动态方法，可用于研究通过组织的运输、曲折度和运输特性。这种厚度分辨的识别策略不仅为复杂样本的成像开辟了新途径，而且有望加速组织病理诊断，与当前的术中病理方法相比，提供更自动化的方案和增强的定量数据。
