Abstract
During recent decades, liquid biopsy has emerged as a promising routine test in clinical diagnostic and prognostic detection due to its simple and non-invasive properties alternative to surgical biopsies in cancer study, among which the circulating tumour cells (CTCs) and exosomes are quite appealing to researchers. However, high throughput is one of the primary constraints to make current cell sorting technologies viable for practical biomedical applications. Practical biomedical analyses typically require the processing of 1-10 mL raw biological sample from patients. Sample purification is generally needed before actual biomedical analysis to improve sensitivity and selectivity. The current cell sorting technologies either require intensive labour (centrifugation) or expensive instrument (traditional fluorescence-activated cell sorting). In this research, we have achieved the rare CTCs collection from heterogenous cell sample with particle diameters in micrometer level (particles>2µm) within Newtonian fluids utilizing the novel inertial device with a series of reverse wavy channel structures. After one single hybrid sorting process we have demonstrated at least 2500-fold purity enrichment of MCF-7 breast cancer cells spiked in diluted whole blood samples with cell viability higher than 89.8%, which is the first hybrid microfluidic cell sorting method, combining high throughput size-dependent inertial sorting and high accuracy fluorescence activated acoustic sorting. Furthermore, we successfully realized exosomes collection from large vesicles with sub-micrometer diameters (or particles<2µm) within non-Newtonian fluids. With an optimized parameters combination, we have demonstrated high throughput size-dependent and label-free sorting of exosomes with purity higher than 92% and recovery higher than 81%. These developed sorting techniques may provide a promising solution in a variety of biomedical research and pharmaceutical applications. Additionally, we have demonstrated dynamically tunable of three separation thresholds ranging from 0.3 to 10 µm by tuning PEO concentrations and flow rates without changing the geometry and dimension of the microfluidic device, providing a helpful spotting in elasto-inertial microfluidic channel operation and biomedical application.