Capture and lyase-triggered release of circulating tumor cells using a disposable microfluidic chip embedded with core/shell nylon-6/Ca(II)-alginate immunofiber mats.

Abstract

High-efficiency capture, release, and reculture of circulating tumor cells (CTCs) can significantly advance individualized cancer treatments. To achieve efficient CTC release without compromising their viability for subsequent reculture, an effective CTC capture/release system was developed. Nylon-6 (N6) and a cross-linked alginate hydrogel with Ca(II) were used as the shell and core, respectively, to prepare N6/Ca-Alg immunofiber mats using coaxial electrospinning. A 3 wt% concentration of Ca(II) was used to increase the viscosity of the alginate solution and generate a degradable coating on the N6 fiber. After modification with streptavidin and anti-EpCAM, the N6/Ca-Alg immunofiber mat was embedded within a disposable microfluidic chip to investigate the capture capacity of CTCs. The maximum adsorption capacity of CTCs was approximately 34 cells per mm², while the viability of the captured cells was 95.1% after being released from the fibrous mats. The outer Ca-alginate hydrogel coating effectively enhanced the viability of the released cells for reculture. In spiked blood samples, our microfluidic system was able to specifically identify DLD1 cells from 10 mL of human whole blood at a concentration of 65.6 cells per mL with 67.9% efficiency within 30 minutes. Under the flow of alginate lyase solution at 0.4 mg mL^-1, the reculture efficiency of the released cells after 7 days reached 274.5%. Our proposed method provides an ideal fibrous mat to be embedded within a microfluidic chip for capturing and releasing CTCs for precision medicine applications, using recultured CTCs in individualized anti-tumor therapies.