Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States; Department of Biomedical Engineering, School of Engineering, University of Alabama at Birmingham, Birmingham, AL, United States.
Department of Surgery, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States.
Anal Chim Acta. 2018 Jul 5;1012:10-29. doi: 10.1016/j.aca.2017.12.050. Epub 2018 Feb 3.
Blood-based liquid biopsies provide a minimally invasive alternative to identify cellular and molecular signatures that can be used as biomarkers to detect early-stage cancer, predict disease progression, longitudinally monitor response to chemotherapeutic drugs, and provide personalized treatment options. Specific targets in blood that can be used for detailed molecular analysis to develop highly specific and sensitive biomarkers include circulating tumor cells (CTCs), exosomes shed from tumor cells, cell-free circulating tumor DNA (cfDNA), and circulating RNA. Given the low abundance of CTCs and other tumor-derived products in blood, clinical evaluation of liquid biopsies is extremely challenging. Microfluidics technologies for cellular and molecular separations have great potential to either outperform conventional methods or enable completely new approaches for efficient separation of targets from complex samples like blood. In this article, we provide a comprehensive overview of blood-based targets that can be used for analysis of cancer, review microfluidic technologies that are currently used for isolation of CTCs, tumor derived exosomes, cfDNA, and circulating RNA, and provide a detailed discussion regarding potential opportunities for microfluidics-based approaches in cancer diagnostics.
基于血液的液体活检提供了一种微创替代方法,可用于识别细胞和分子特征,这些特征可作为生物标志物用于检测早期癌症、预测疾病进展、纵向监测化疗药物反应,并提供个性化的治疗选择。可用于详细分子分析以开发高度特异性和敏感性生物标志物的血液中的特定靶标包括循环肿瘤细胞 (CTC)、源自肿瘤细胞的外泌体、无细胞循环肿瘤 DNA (cfDNA) 和循环 RNA。鉴于血液中 CTC 和其他肿瘤衍生产物的含量低,液体活检的临床评估极具挑战性。用于细胞和分子分离的微流控技术具有很大的潜力,可以超越传统方法或能够从血液等复杂样本中高效分离目标的全新方法。在本文中,我们全面概述了可用于癌症分析的基于血液的靶标,综述了目前用于分离 CTC、肿瘤衍生外泌体、cfDNA 和循环 RNA 的微流控技术,并详细讨论了基于微流控的方法在癌症诊断中的潜在机会。