Inverse 3D ‘lab-on-a-chip’ polymeric microfilms for selective capture of circulating tumor cells from patients’ blood

Abstract

Engineering inverse 3D polymeric microfilms with controlled spatial hierarchy is highly challenging and important at the crossroads of biology and material science due to its potential in enhancing selective cell surface interactions such as in cell adhesion and growth. Protein-modified inverse 3D polymeric microfilms, could thus similarly promote selective cell capture and adhesion. We report the fabrication of inverse 3D polymeric microfilms using composite polymeric-bioligand conjugated films for enhanced capture of circulating tumor cells (CTCs) from cancer patients’ blood. The microfilms were designed using functionalized poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA), mediated with ligand transferrin. Protein immobilization on the films was achieved by conjugating transferrin (Tf), collagen (Co), and bovine serum albumin (BSA) for promoting cellular adhesion and capture. The films were evaluated using scanning electron microscopy (SEM), infrared spectroscopy (ATR-IR) and contact angle (θ) measurements, and demonstrated micro-pores ranging from 18-26 µm. Confocal laser scanning microscopy (CLSM) revealed enhanced cell attachment on the polymeric-blend microfilms evidencing enhanced cell adhesion, capture, and further the ability to proliferate in the 3D space. The inverse 3D polymeric microfilms demonstrated an 80% cell capture efficiency using cultured cancer cells. In a clinical utility, the CTC capturing efficiency was comparable with OncoDiscover® CTC enumeration technology. The inverse 3D polymeric microfilms present a novel ‘lab-on-a-chip’ platform to enable enumeration of CTCs for monitoring minimal residual disease (MRD), progress of metastasis, response to treatment, and finally in early detection of relapse.