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Microfluidic applications on circulating tumor cell isolation and biomimicking of cancer metastasis
Authors:Xiawei Xu  Zhenqi Jiang  Jing Wang  Yong Ren  Aiguo Wu
Institution:1. Cixi Institute of Biomedical Engineering, CAS Key Laboratory of Magnetic Materials and Devices, & Key Laboratory of Additive Manufacturing Materials of Zhejiang Province, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, P. R. China

Research Group for Fluids and Thermal Engineering, University of Nottingham Ningbo China, Ningbo, P. R. China

Department of Mechanical, Materials and Manufacturing Engineering, University of Nottingham Ningbo China, Ningbo, P. R. China;2. Cixi Institute of Biomedical Engineering, CAS Key Laboratory of Magnetic Materials and Devices, & Key Laboratory of Additive Manufacturing Materials of Zhejiang Province, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, P. R. China;3. Department of Electrical and Electronic Engineering, University of Nottingham Ningbo China, Ningbo, P. R. China;4. Research Group for Fluids and Thermal Engineering, University of Nottingham Ningbo China, Ningbo, P. R. China

Abstract:The prognosis of malignant tumors is challenged by insufficient means to effectively detect tumors at early stage. Liquid biopsy using circulating tumor cells (CTCs) as biomarkers demonstrates a promising solution to tackle the challenge, because CTCs play a critical role in cancer metastatic process via intravasation, circulation, extravasation, and formation of secondary tumor. However, the effectiveness of the solution is compromised by rarity, heterogeneity, and vulnerability associated with CTCs. Among a plethora of novel approaches for CTC isolation and enrichment, microfluidics leads to isolation and detection of CTCs in a cost-effective and operation-friendly way. Development of microfluidics also makes it feasible to model the cancer metastasis in vitro using a microfluidic system to mimick the in vivo microenvironment, thereby enabling analysis and monitor of tumor metastasis. This paper aims to review the latest advances for exploring the dual-roles microfluidics has played in early cancer diagnosis via CTC isolation and investigating the role of CTCs in cancer metastasis; the merits and drawbacks for dominating microfluidics-based CTC isolation methods are discussed; biomimicking cancer metastasis using microfluidics are presented with example applications on modelling of tumor microenvironment, tumor cell dissemination, tumor migration, and tumor angiogenesis. The future perspectives and challenges are discussed.
Keywords:cancer metastasis  circulating tumor cells  isolation  lab-on-a-chip  microfluidics
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