Abstract
The selection of circulating tumor cells (CTCs) directly from blood as a real-time liquid biopsy has received increasing attention over the past ten years, and further analysis of these cells may greatly aid in both research and clinical applications. CTC analysis could advance understandings of metastatic cascade, tumor evolution, and patient heterogeneity, as well as drug resistance. Until now, the rarity and heterogeneity of CTCs have been technical challenges to their wider use in clinical studies, but microfluidic-based isolation technologies have emerged as promising tools to address these limitations. This review provides a detailed overview of latest and leading microfluidic devices implemented for CTC isolation. In particular, this study details must-have device performances and highlights the tradeoff between recovery and purity. Finally, the review gives a report of CTC potential clinical applications that can be conducted after CTC isolation. Widespread microfluidic devices, which aim to support liquid-biopsy-based applications, will represent a paradigm shift for cancer clinical care in the near future.
Highlights
Institut Lumière Matière ILM-UMR 5306, CNRS, Université Lyon 1, 69622 Villeurbanne, France; Abstract: The selection of circulating tumor cells (CTCs) directly from blood as a real-time liquid biopsy has received increasing attention over the past ten years, and further analysis of these cells may greatly aid in both research and clinical applications
Some of the most promising hydrodynamic isolation strategies can be classified into size-dependent deterministic flow pathways in pillar arrays, inertial migration of cells in a multi-flow straight microchannel, inertial focusing in spiral microfluidic channels, and microfluidic vortices generated in micro-reservoirs aside the channel
Vortex HT chip enabled the coupling of in-flow, label-free cell enumeration on bright-field images with various standard assays downstream, such as cytology and cytogenetics [73]. They assessed the feasibility of characterizing the anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangement by fluorescence in situ hybridization (FISH) in CTCs isolated from patients with non-small-cell lung cancer (NSCLC)
Summary
Cancer is a leading health issue, accounting for nearly 1 in 6 deaths worldwide. By. The main issue is the rarity of CTCs (1–1000 CTCs per mL) among a high background of blood cells (109 red blood cells (RBCs) and 107 white blood cells (WBCs) per mL) Their isolation is challenging, due to th following characteristics: (i) a morphology similarity with some WBCs, reducing size-based sorting effectiveness; (ii) a phenotypic heterogeneity, which makes the use of biomarkers more complex and limits the effectiveness of biomarker-based separation. Besides requiring different kits depending on the cancer type, the isolation of CTCs from the plasma and density gradient interface is extremely challenging and may further compromise their biological integrity Another approach based on their size, the ISET (isolation by size of epithelial tumor cells, RareCells, France) kit is used to isolate CTCs [12]; to CellSearchTM, this method only monitors epithelial cells. There is still an unmet need for specific and sensitive isolation of clinically relevant CTCs, required for their further characterization
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