Open AccessDesign and validation of a tunable inertial microfluidic system for the efficient enrichment of circulating tumor cells in blood
Author(s) -
RodríguezPena Alejandro,
Armendariz Estibaliz,
Oyarbide Alvaro,
Morales Xabier,
OrtizEspinosa Sergio,
RuizFernández de Córdoba Borja,
Cochonneau Denis,
Cornago Iñaki,
Heymann Dominique,
Argemi Josepmaría,
D'Avola Delia,
Sangro Bruno,
Lecanda Fernando,
Pio Ruben,
CortésDomínguez Iván,
OrtizdeSolórzano Carlos
Publication year - 2022
Publication title -
bioengineering and translational medicine
Language(s) - English
Resource type - Journals
ISSN - 2380-6761
DOI - 10.1002/btm2.10331
Subject(s) - circulating tumor cell , microfluidics , biomedical engineering , computer science , whole blood , materials science , cancer , nanotechnology , medicine , surgery , metastasis
The analysis of circulating tumor cells (CTCs) in blood is a powerful noninvasive alternative to conventional tumor biopsy. Inertial‐based separation is a promising high‐throughput, marker‐free sorting strategy for the enrichment and isolation of CTCs. Here, we present and validate a double spiral microfluidic device that efficiently isolates CTCs with a fine‐tunable cut‐off value of 9 μm and a separation range of 2 μm. We designed the device based on computer simulations that introduce a novel, customized inertial force term, and provide practical fabrication guidelines. We validated the device using calibration beads, which allowed us to refine the simulations and redesign the device. Then we validated the redesigned device using blood samples and a murine model of metastatic breast cancer. Finally, as a proof of principle, we tested the device using peripheral blood from a patient with hepatocellular carcinoma, isolating more than 17 CTCs/ml, with purity/removal values of 96.03% and 99.99% of white blood cell and red blood cells, respectively. These results confirm highly efficient CTC isolation with a stringent cut‐off value and better separation results than the state of the art.