Self-assembled coronene nanofiber arrays: toward integrated organic bioelectronics for efficient isolation, detection, and recovery of cancer cells

Abstract

The biological immobilization of antibodies onto geometrically controlled conducting/semiconducting nanostructures is a promising approach for directing efficient cell–substrate interactions at bioelectronic interfaces (BEIs), thereby facilitating the melding of biological systems with electronics. In this study, we employed a novel thin-film growth technology to fabricate three-dimensional (3D) organic small-molecule semiconductor-based nanofiber (NF) arrays on transparent conducting electrodes, and examined their BEI integration for the isolation, detection, and recovery of circulating tumor cells (CTCs). During normal thermal evaporation, out-of-plane nanostructures of coronene (CR), a polycyclic aromatic small molecule, readily formed through template-assisted self-assembly. We exploited the synergistic effects of controllable CR-based NF structures and anti-epithelial cellular adhesion molecule (anti-EpCAM) coatings as nanovelcro cell-affinity assays to enhance the capture efficiency of targeted CTCs, while behaving as anti-adhesive surfaces for non-targeted cells. Because of the high integration capability and high optical transparency of CR-based NFs, optimizing the binding conditions of the anti-EpCAM coatings allowed us to develop a liquid biopsy chip for the selective capture of CTCs and for the rapid/direct quantification (using a normal inverted optical microscope) of the number of captured CTCs; in addition, we designed this system such that it would allow electrically driven cell-release (using an electrochemical potentiostat). The desorption phenomena of PLL-g-PEG–biotin upon applying 20 cycles of cyclic voltammetry (voltage swept from 0 to +1.0 V) in PBS buffer triggered the electrical release of the captured CTCs from the CR-based NFs; integration of the CR-based NF substrate with an overlaid microfluidic PDMS chaotic mixer led to highly efficient cell-capture yields (>84%) at various spiked densities of MCF7 cells in a THP-1 cell solution (10⁶ cells per mL); over 90% of the resulting cells were viable. These 3D CR-based BEI devices suggest that new opportunities abound in the design of novel organic electronics for advanced biomedical applications.