Microfluidic applications on circulating tumor cell isolation and biomimicking of cancer metastasis

Abstract

Microfluidic applications on circulating tumor cell isolation and biomimicking of cancer metastasisThe 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.

EMT-Associated Heterogeneity in Circulating Tumor Cells: Sticky Friends on the Road to Metastasis

“…The prominent place progressively taken by microfluidics in the CTC field within the last decade is worth highlighting [19][20][21][22][23]. Microfluidics has indeed emerged as an innovative approach to directly process whole blood, to use small amounts of reagents, and to reduce cost.…”

“…Conversely, negative selection approaches have also been developed. If many of these systems use immunomagnetic sorting, microfluidic-based enrichment technologies have also emerged, in which different supports coated with specific antibodies are precisely disposed in the flow so as to favor cell-antibody interactions [19][20][21][22][23][24][25][26][27][28][29][30]. Interestingly, aptamers are gaining major interest as an alternative to antibodies in positive selection-based CTC enrichment, and have for instance been exploited in magnetic bead separation assays or in microfluidic devices [31,32].…”

Bladder cancer hunting: A microfluidic paper‐based analytical device

“…Relying on the appearance of the wax-printing printer, the fabrication procedure of μPAD can be greatly simplified. The application of colloidal gold-labeling technology makes the test results visible to the naked eye without any equipment, and only about 3-10 min are needed to complete the experiment, which is better than that of any other methods such as clinical cystoscopy [37], cytology [2,38], detection of urinary extracellular vesicles [39], or CTCs [40,41] with the microfluidic chip and any biomarker [42]. More importantly, although simple, the chip can simultaneously find two specific biomarkers, and double the accuracy of bladder cancer detection results, making the detection efficiency of the μPAD better than the existing detection methods.…”

Detection of circulating tumor cells: Advances and critical concerns (Review)

“…A novel approach used to enrich CTCs relies on unique hydrodynamics and is used in microfluidic channels (87)(88)(89). The hydrodynamics method is primarily based on the different movements of cells with different sizes in response to the hydrodynamic force (90). There are three main types, which are separately detailed below: Deterministic lateral displacement (DLD), inertial focusing and micro-vortex (90).…”