In a study published in Biosensors and Bioelectronics, a research group led by WU Yihui from Changchun Institute of Optics, Fine Mechanics and Physics (CIOMP) of the Chinese Academy of Sciences (CAS) proposed a design method for multistage label-free microfluidic cell sorting chip. 

Circulating tumor cells (CTCs) are the tumor cells present in peripheral blood. By detecting CTCs in peripheral blood, tumor dynamics can be monitored in real time and therapeutic effects can be evaluated. Sorting methods of CTCs with high purity, efficiency, and cell viability become the key to the clinical applications. 

The researchers classified CTCs into three sizes with large, medium, and small diameters. Only a small number of CTCs are in medium diameter, and are not easily isolated by size-based microfluidic techniques due to the interference of leukocytes. Within the droplet-shaped microcolumn (DMC) two-array deterministic lateral displacement (DLD) chip, small-diameter cells maintained Zigzag mode motion at the bottom of the chip throughout. Medium- and large-diameter cells moved to the middle of the chip in a migratory mode in the first array and separated in the second array. 

The researchers sorted out three sizes of cells from the bottom outlet, the middle outlet and the top outlet, respectively. The medium-diameter CTCs and leukocytes were purified through cone channel chips. Stiffer leukocytes were entrapped while softer CTCs passed through the channel. The cell types were identified using a Raman spectrometer, which is compatible with label-free sorting chips.

The entire CTCs sorting and analysis process was label free, highly pure, high-throughput and efficient. Attributed to the excellent fluid regulation capability of DMC, the CTCs sorter system developed by parallelizing four DMC two-array DLD chips was able to process a sample of 2.5 mL per minute with a recovery efficiency of 96.30±2.10% and a purity of 98.25±2.48%.

This study provides a new perspective for using multiple physical properties to classify CTCs, which can improve specificity and reduce the impact of heterogeneity.