Progress in Circulating Tumor Cell Research Using Microfluidic Devices

Abstract

Circulating tumor cells (CTCs) are a popular topic in cancer research because they can be obtained by liquid biopsy, a minimally invasive procedure with more sample accessibility than tissue biopsy, to monitor a patient’s condition. Over the past decades, CTC research has covered a wide variety of topics such as enumeration, profiling, and correlation between CTC number and patient overall survival. It is important to isolate and enrich CTCs before performing CTC analysis because CTCs in the blood stream are very rare (0–10 CTCs/mL of blood). Among the various approaches to separating CTCs, here, we review the research trends in the isolation and analysis of CTCs using microfluidics. Microfluidics provides many attractive advantages for CTC studies such as continuous sample processing to reduce target cell loss and easy integration of various functions into a chip, making “do-everything-on-a-chip” possible. However, tumor cells obtained from different sites within a tumor exhibit heterogenetic features. Thus, heterogeneous CTC profiling should be conducted at a single-cell level after isolation to guide the optimal therapeutic path. We describe the studies on single-CTC analysis based on microfluidic devices. Additionally, as a critical concern in CTC studies, we explain the use of CTCs in cancer research, despite their rarity and heterogeneity, compared with other currently emerging circulating biomarkers, including exosomes and cell-free DNA (cfDNA). Finally, the commercialization of products for CTC separation and analysis is discussed.

The Role of Circulating Tumor Cells in the Metastatic Cascade: Biology, Technical Challenges, and Clinical Relevance

“…However, biophysical-based CTC selection needs to be supported by molecular-based CTC detection. Microfluid systems have been commercialized, but such sophisticated systems need to be automated and this increases the cost of such devices, thus limiting their implementation [133].…”

Evaluation of circulating tumor cell clusters for pan‐cancer noninvasive diagnostic triaging

“…Clinical details of these patients' cancers were determined from the most recent clinical reports. Finally, the study evaluated 13 Tables 2 and 3, respectively. All study participants were counselled regarding the aims and scope of each study, after which they provided signed, written informed consent.…”

Microfluidics for Biomedical Analysis

“…The microfluidic approaches, which consume a very low volume of reagents (e.g., antibody, magnetic nanoparticles) and can deal with a considerable volume of samples in a continuous manner, have become an increasingly important tool for separating CTCs from normal cells. In the last decade, the scientists have developed microfluidic system‐based CTC‐detecting methods by using the unique properties of CTCs (e.g., density, size, deformability, and the differences in membrane protein expression) . Recently, researchers have profiled the protein expression in CTCs by using microfluidic WB.…”