Department of Pharmaceutical Sciences, Department of Chemistry, University of Toronto, Toronto, ON, M5S 3M2, Canada.
Angew Chem Int Ed Engl. 2020 Feb 10;59(7):2554-2564. doi: 10.1002/anie.201905005. Epub 2019 Nov 7.
Circulating tumour nucleic acids (ctNAs) are released from tumours cells and can be detected in blood samples, providing a way to track tumors without requiring a tissue sample. This "liquid biopsy" approach has the potential to replace invasive, painful, and costly tissue biopsies in cancer diagnosis and management. However, a very sensitive and specific approach is required to detect relatively low amounts of mutant sequences linked to cancer because they are masked by the high levels of wild-type sequences. This review discusses high-performance nucleic acid biosensors for ctNA analysis in patient samples. We compare sequencing- and amplification-based methods to next-generation sensors for ctDNA and ctRNA (including microRNA) profiling, such as electrochemical methods, surface plasmon resonance, Raman spectroscopy, and microfluidics and dielectrophoresis-based assays. We present an overview of the analytical sensitivity and accuracy of these methods as well as the biological and technical challenges they present.
循环肿瘤核酸(ctNAs)由肿瘤细胞释放,可以在血液样本中检测到,为无需组织样本即可追踪肿瘤提供了一种方法。这种“液体活检”方法有可能替代癌症诊断和管理中侵入性、痛苦和昂贵的组织活检。然而,由于它们被高水平的野生型序列掩盖,因此需要非常敏感和特异的方法来检测与癌症相关的相对低量的突变序列。本文综述了用于分析患者样本中 ctNA 的高性能核酸生物传感器。我们将基于测序和扩增的方法与下一代 ctDNA 和 ctRNA(包括 microRNA)分析传感器(如电化学方法、表面等离子体共振、拉曼光谱以及基于微流控和介电泳的分析)进行了比较。我们介绍了这些方法的分析灵敏度和准确性的概述,以及它们所面临的生物学和技术挑战。