Negative Isolation of Circulating Tumor Cells Using a Microfluidic Platform Integrated with Streptavidin-Functionalized PLGA Nanofibers

Abstract

Abstract

Detection of circulating tumor cells (CTCs) plays an important role in early diagnosis of cancer and personalized therapy. However, isolated CTCs, especially those captured by positive sorting methods, are difficult to culture in subsequent assays because the cells have to be labeled or attached to a substrate for separation. In this study, a negative sorting method has been developed for isolation of CTCs through a microfluidic platform integrated with streptavidin-functionalized electrospun polylactic-co-glycolic acid nanofibers. Through the specific biotin-streptavidin interaction, the device is able to sort out biotinylated anti-CD45 antibody-labeled white blood cells (WBCs) and enrich A549 human cancer cells from the blood or CTCs from patient suffering non-small cell lung cancer. We demonstrate that the WBC capture efficiency is as high as 97.0%, and the recovery rate of cancer cells reaches up to 97.5%. CTCs are enumerated from blood samples of patients suffering lung carcinoma. The number of CTCs increased with the progression of NCCN TNM stages and showed statistically significant difference between stage I and later stages. These results suggest that the integrated negative sorting device is promising to be used for diagnosis of cancer.

Graphic Abstract

Funding

National Natural Science Foundation of China(81761148028); Science and Technology Commission of Shanghai Municipality(19XD1400100); Shanghai Education Commission through the Shanghai Leading Talents Program, and the 111 Project(BP0719035)