Analytical Validation of a Spiral Microfluidic Chip with Hydrofoil-Shaped Pillars for the Enrichment of Circulating Tumor Cells

Date

2023-10-01

Author

Sen-Dogan, Begum
Demir, Mehmet Alper
Sahin, Buket
Yıldırım, Ender
Karayalcin, Gizem
Sahin, Sebnem
Mutlu, Ege
Toral, Taylan Berkin
Ozgur, Ebru
Zorlu, Ozge
Kulah, Haluk

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The isolation of circulating tumor cells (CTCs) from peripheral blood with high efficiency remains a challenge hindering the utilization of CTC enrichment methods in clinical practice. Here, we propose a microfluidic channel design for the size-based hydrodynamic enrichment of CTCs from blood in an epitope-independent and high-throughput manner. The microfluidic channel comprises a spiral-shaped part followed by a widening part, incorporating successive streamlined pillars, that improves the enrichment efficiency. The design was tested against two benchmark designs, a spiral microfluidic channel and a spiral microfluidic channel followed by a widening channel without the hydrofoils, by processing 5 mL of healthy blood samples spiked with 100 MCF-7 cells. The results proved that the design with hydrofoil-shaped pillars perform significantly better in terms of recovery (recovery rate of 67.9% compared to 23.6% in spiral and 56.7% in spiral with widening section), at a cost of slightly lower white blood cell (WBC) depletion (depletion rate of 94.2% compared to 98.6% in spiral and 94.2% in spiral with widening section), at 1500 µL/min flow rate. For analytical validation, the design was further tested with A549, SKOV-3, and BT-474 cell lines, yielding recovery rates of 62.3 ± 8.4%, 71.0 ± 6.5%, and 82.9 ± 9.9%, respectively. The results are consistent with the size and deformability variation in the respective cell lines, where the increasing size and decreasing deformability affect the recovery rate in a positive manner. The analysis before and after the microfluidic chip process showed that the process does not affect cell viability.

Subject Keywords

circulating tumor cell (CTC) separation, computational fluid dynamics, inertial hydrodynamics, microfluidic channel

URI

https://hdl.handle.net/11511/106277

Collections

Department of Mechanical Engineering, Article