Isolation and trypsin-trigged release of circulating tumor cells from core/shell nylon-6/methacrylated gelatin immunofiber mats for reculture through microfluidic chips

Chien-Hsing Lu, Fu-Xiang Lin, Shien-Kuei Liaw, Hsia-Wei Liu, and Jem-Kun Chen

International Journal of Biological Macromolecules, Volume 343, Part 1, February 2026

Abstract

A novel approach has been developed to efficiently isolate and reculture model circulating tumor cells (mCTCs) using a fiber-based microfluidic platform. This system features a core–shell structure composed of a polycaprolactam (Ny) core and a outer layer of cross-linked methacrylated gelatin (GelMA) infused with a photoinitiator (PI). The Ny/GelMA composite immunofiber mats are fabricated via coaxial electrospinning, where a PI concentration of 1.5 wt% enhances the viscosity of the GelMA, forming a degradable inner coating on the Nylon fibers. Functionalization with streptavidin and anti-EpCAM antibodies allows the mats to selectively bind mCTCs when integrated into a single-use microfluidic chip. The platform demonstrated a peak mCTC binding density of around 61.1 cells/mm2 and maintained a post-release cell viability of 98.9%, indicating minimal damage during retrieval. The GelMA coating played a key role in preserving cell integrity and supporting their subsequent in vitro expansion. In blood spiking experiments, the chip effectively recovered SKOV3 cells from 10 mL samples of whole blood at 96.6 cells/mL, achieving a capture rate of 83.3% within 1 h. When treated with 0.06 wt% trypsin, the released SKOV3 cells exhibited a proliferation efficiency of 167.5% after six days in culture. This fiber-integrated microfluidic system provides a promising tool for the gentle and selective capture of viable mCTCs, supporting downstream culturing for use in tailored cancer treatment strategies and the broader field of precision oncology.

Keywords

Coaxial electrospinning ; Circulating tumor cells ; GelMA ; Trypsin