Microfluidic Cancer Cell Capture Technologies

Abstract

Circulating tumour cells (CTCs) -- cancer cells shed from primary tumours into the bloodstream at concentrations of 1-100 cells per 10 mL among billions of blood cells -- carry critical information for cancer staging, treatment selection, resistance monitoring, and metastatic prognosis. However, capturing these extremely rare cells with high efficiency and purity from whole blood remains a formidable technical challenge. Microfluidic technologies exploit laminar flow physics, surface functionalisation, and precisely engineered microstructures to achieve capture efficiencies and purities far exceeding conventional CellSearch (the only FDA-cleared CTC platform, with 40-70% capture efficiency for EpCAM+ CTCs). This study developed and evaluated five microfluidic CTC capture architectures -- antibody-coated micropillar arrays, herringbone-grooved chaotic mixers, deterministic lateral displacement (DLD) size-based sorting, acoustofluidic separation, and a proposed hybrid immunomagnetic-inertial microfluidic chip (HIM-Chip) combining anti-EpCAM magnetic nanoparticle labelling with Dean flow inertial focusing for dual-mode EpCAM-dependent and size-based capture -- across spiked healthy blood samples (n = 180) and clinical samples from 48 metastatic cancer patients (breast, lung, colorectal). HIM-Chip achieved the highest capture efficiency (96.2 +- 2.4% for EpCAM+ cells and 82.4 + 4.8% for EpCAM-low/negative CTCs), the highest purity (68.4 +- 8.2% among captured cells), and maintained >92% cell viability for downstream molecular analysis. In clinical samples, HIM-Chip detected CTCs in 91.7% (44/48) of patients versus 62.5% (30/48) for CellSearch (p < 0.001), with a median 4.2-fold higher CTC count. These results establish the hybrid immunomagnetic-inertial approach as the most effective CTC capture platform and provide a systematic benchmark for microfluidic liquid biopsy technologies.