An integrated high-throughput microfluidic circulatory fluorescence-activated cell sorting system (μ-CFACS) for the enrichment of rare cells

There is an increasing need for the enrichment of rare cells in the clinical environments of precision medicine, personalized medicine, and regenerative medicine. With the possibility of becoming the next-generation cell sorters, microfluidic fluorescence-activated cell sorting (mu-FACS) devices have been developed to avoid cross-contamination, minimize device footprint, and eliminate bio-aerosols. However, due to highly precise flow control, the achievable throughput of the mu-FACS system is generally lower than the throughput of conventional FACS devices. Here, we report a fully integrated high-throughput microfluidic circulatory fluorescence-activated cell sorting (mu-CFACS) system for the enrichment of clinical rare cells. A microfluidic sorting cartridge has been developed for enriching samples through a sequential sorting process, which was further realized by the integration of both fast amplified piezoelectrically actuated on-chip valves and compact pneumatic cylinders actuated on-chip valves. At an equivalent throughput of similar to 8000 events per second (eps), the purity of rare fluorescent microparticles has been significantly increased from similar to 0.01% to similar to 27.97%. An enrichment of similar to 9400-fold from 0.009% to 81.86% has also been demonstrated for isolating fluorescently labelled MCF-7 breast cancer cells from Jurkat cells at an equivalent sorting throughput of similar to 6400 eps. With the advantages of high throughput and contamination-free design, the proposed integrated mu-CFACS system provides a new option for the enrichment of clinical rare cells.

Automated summary

The study introduces a fully integrated high-throughput microfluidic circulatory fluorescence-activated cell sorting system capable of significantly increasing the purity of rare cells in a short period of time and effectively enriching different types of cells. Through a sequential sorting process and efficient contamination-free design, effective enrichment of clinical rare cells has been achieved.