Precise and non-invasive circulating tumor cell isolation based on optical force using homologous erythrocyte binding

Abstract

Precise isolation of circulating tumor cells (CTCs) is proved to be significant for early cancer diagnosis and downstream analysis. Most of the existing strategies yield low purity or cause unexpected damage to cells because of foreign material introduction. To avoid foreign material caused damage and achieve high efficiency simultaneously, this work presents an innovative strategy using tumor cell targeting molecules to bind homologous red blood cells (RBCs) with tumor cells, which results in obvious optical constant differences (both size and mean refractive index) between CC-RBCs (RBC conjugated CTCs) and other blood cells. Then the modified CTCs can be precisely separated under laser illumination in an optofluidic system. Experiments show that CTCs are efficiently modified with erythrocytes and finally isolated from blood at high purity (more than 92%) and a high recovery rate (over 90%). In the whole process, CTCs are proved to keep membrane and function integrity. The combination of homologous RBC binding and an optofluidic system will provide a convenient tool for cancer early diagnosis and treatment monitoring, which exhibits good performance in CTC non-invasive and precise isolation, thus showing great potential.