High-throughput concentration of rare malignant tumor cells from large-volume effusions by multistage inertial microfluidics

Abstract

On-chip concentration of rare malignant tumor cells (MTCs) in malignant pleural effusions (MPEs) with a large volume is challenging. Previous microfluidic concentrators suffer from a low concentration factor (CF) and a limited processing throughput. This study describes a low-cost multiplexed microfluidic concentrator that can enable high-throughput (up to 16 mL min⁻¹) and high CF (over 40-fold for single run) concentration of rare cells from large-volume biofluids (up to hundreds of milliliters). The multiplexed device was fabricated using inexpensive polymer-film materials using a quick non-clean-room process within 30 min. The multiplexing and flow distribution approaches applied in the device achieved high-throughput processing. By adopting serial cascading, an ultrahigh CF of approximately 1400 was achieved. Moreover, the microfluidic concentrator was successfully applied for the concentration and purification of rare MTCs within MPEs collected from patients with advanced metastatic lung and breast cancers. The provision of concentrated samples with low background cells could improve the sensitivity of cytology and thus reduce the time required for cytological examination. This novel concentrator offers the distinct advantages of a remarkable CF, high throughput, low device cost, and label-free processing and can therefore be readily integrated with other on-chip cell sorters to enhance the identification of MPEs.