Isolation of circulating tumor cells in non-small-cell-lung-cancer patients using a multi-flow microfluidic channel

Abstract

Circulating tumor cells (CTCs) carry a wealth of information on primary and metastatic tumors critical for precise cancer detection, monitoring, and treatment. Numerous microfluidic platforms have been developed in the past few years to capture these rare cells in patient bloodstream for deciphering the critical information needed. However, the practical need for a high-quality method of CTC isolation remains to be met. Herein, we demonstrate a novel multi-flow microfluidic device that is able to sensitively provide high purity (>87%) of separation outcome without labeling. Our device is constructed and configured based on the phenomenal effect of size-dependent inertial migration. The recovery rate of >93% has been achieved using spiked cancer cells at clinically relevant concentrations (10 cells per 5 mL and above). We have also successfully detected CTCs from 6 out of 8 non-small-cell-lung-cancer (NSCLC) patients, while none for 5 healthy control subjects. With these results, we envision our approach is a promising alternative for reliable CTC capture, and thus for facilitating the progress of extracting information from CTCs to personalize treatment strategies for solid tumor patients.

Circulating biomarkers in patients with glioblastoma

“…47,81 Other approaches to CTC isolation rely on differences in their physical property and use techniques, such as filtration, chip technology, density gradient centrifugation, electric field, sound waves 82 and microfluidic technology. 54,[83][84][85] Characterisation of CTCs can be performed by using immunocytochemistry, molecular technologies and/or functional assays. 47 Currently, the only FDA-approved platform for the isolation of CTCs is the CellSearch® system (Menarini Silicon Biosystems, Italy), which relies on the positive selection of tumour cells overexpressing an epithelial cell adhesion marker, EpCAM.…”

Evaluation of Performance and Tunability of a Co-Flow Inertial Microfluidic Device

“…Flow rate ratio can impact the separation performance of a co-flow inertial system by controlling initial lateral positions of the suspended particles [20]. In this co-flow system, we defined flow rate ratio as the sample flow rate over the buffer flow rate.…”

“…This is especially true in inertial microfluidics, where microparticles have been and still are used to demonstrate new devices concepts, understand device performance and elucidate device physics [3,[17][18][19][20][21][22][23][24][25][26][27][28][29]. These experiments often determine the separation efficiency and the resulting device physics [3,[17][18][19][20][21][22][23][24][25][26][27][28][29]. These experiments often determine the separation efficiency and the resulting purity, allowing for optimization of flow conditions without wasting any of the biological sample.…”

Recent Advances in Microfluidic Platforms Applied in Cancer Metastasis: Circulating Tumor Cells' (CTCs) Isolation and Tumor‐On‐A‐Chip

“…In addition, Zhou et al employed a multiflow microfluidic platform based on the principle of size‐dependent inertial migration to attain high purity (more than 87%) and recovery rate (more than 93%) of CTCs' capture from spiked cancer cells at the concentration of 10 cells per 5 mL blood. Moreover, CTCs in 6/8 NSCLC patients were detected by the same platform and none was observed at 5 health control samples …”