Description
The isolation of Circulating Tumor Cells (CTCs) directly from blood by liquid biopsy could lead to a paradigm shift in clinical cancer care by contributing to earlier diagnosis and the development of personalized treatment [1]. Nevertheless, CTCs must be recovered with high recovery rates and high purity within a short processing time, and through a user-friendly workflow. These specific requirements have so far limited the use of CTCs in clinical studies. The main issues lie in efficiently separating CTCs from white blood cells (WBCs), as they are present at ultra-low concentrations in blood (approximately 10 CTC and 10^7 WBCs for 1mL of blood). Several microfluidic methods have been developed to isolate CTCs from other blood cells, either by exploiting biological properties differences, a sorting approach complexified by the heterogeneity of cell surface markers, or by relying on physical properties differences such as size, deformability, and dielectric properties. While this latter approach enables high-throughput, label-free processing, the strong overlap in physical properties between CTCs and other blood cells limits its potential of separation. As a result, although numerous systems have been developed, there is currently no device that fully meets the required performance criteria in terms of CTC recovery [2] .
In this work, we aim at combining these two separation strategies on a single microfluidic chip, to benefit from the high purity of this combination, while minimizing the risk of CTC loss associated with sample manipulation.
First, we developed a compatible pre-enrichment module based on size discrimination using Dean vortices. The spiral-shaped channel generates secondary flows perpendicular to the main stream, resulting in size-dependent particle trajectories. Different spiral geometries were tested, varying the width, aspect ratio, or cross-sectional shape of the channel to achieve cell separation at a flow rate compatible with the downstream immunomagnetic function. The optimal design allowed for effective separation between white blood cells and CTC-mimicking cells (HCC827, MDA, MCF7, PC3) at a flow rate of 50 mL/h [3].
This immunomagnetic sorting function implements an array of ferromagnetic microtraps to capture remaining WBCs, magnetically labeled [4]. It has been improved to operate at compatible flow rates with high WBC capture efficiency, by optimizing channel section, labeling percentage, WBC concentration and chip-to-magnet distance. Capture performances were assessed with magnetically labeled WBCs from whole blood sample. The immunomagnetic chip demonstrates high capture rates, achieving over 94% WBC capture at 30 mL/h and maintaining strong efficiencies at high flow rates, with more than 80% capture at 120 mL/h. These results, showing high capture performances for both microfluidic functions at comparable operating flow rates, are promising for their integration onto a single chip, enabling CTC sorting with high recovery, purity, and robust overall performance.
[1] T. N. A. Nguyen, et al., Cancers, vol. 15, no 22, 2023, doi: 10.3390/cancers15225372.
[2] Z. Qiao, X. Teng, et al., Micromachines, vol. 15, no 6, 2024, doi: 10.3390/mi15060706.
[3] E. Dupont et al., Proceedings of BOISTEC Conference, 2025, p.163‑170. doi: 10.5220/0013162200003911.
[4] L. Descamps et al., Lab. Chip, vol. 22, no 21, 2022, doi: 10.1039/D2LC00443G.