Integration of aligned polymer nanofibers within a microfluidic chip for efficient capture and rapid release of circulating tumor cells

Abstract

Capture and detection of circulating tumor cells (CTCs) is of great significance in the early diagnosis, prognosis evaluation and personalized therapy of cancer. Herein, we report a unique microfluidic platform integrated with zwitterion-modified aligned polyethyleneimine/polyvinyl alcohol nanofibers for efficient capture and rapid release of CTCs. We show that zwitterions of poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) can be immobilized onto the aligned nanofibers via an atomic transfer radical polymerization approach. The combined strategy of using aligned nanofibers instead of random nanofibers and PMPC immobilization endows the nanofibers with excellent antifouling properties against protein adsorption and blood cell attachment, thereby significantly improving the capture purity of cancer cells. Meanwhile, the targeting ligand folic acid (FA) can be modified onto the surface of nanofibers via a redox-sensitive disulfide bond to specifically and efficiently capture cancer cells overexpressing FA receptors and to rapidly release the cancer cells in a non-destructive manner through tris(2-carboxyethyl)phosphine treatment. The dynamic capture assay using the fiber-integrated microfluidic platform demonstrates that FA receptor-expressing cancer cells can be isolated with a high capture efficiency (92.7%) and considerable purity (43.4%) in a time period of 30 min and can be rapidly detached from the nanofibrous substrates within 5 min with a release efficiency up to 98.9%. These results as well as the isolation and detection of CTCs from the blood of cancer patients suggest that the developed microfluidic chip may be potentially used for clinical cancer diagnosis applications.