Versatile Organic Electrochemical Transistors with Self-Assembled Coronene Nanofiber Arrays for the Isolation and Detection of Circulating Tumor Cells and Enhanced Secretion of Extracellular Vesicles.

The integration of organic bioelectronic interfaces has opened new avenues for merging biological systems with electronics, offering transformative solutions to challenges in both fields. In this study, we present a novel hybrid organic electrochemical transistor (OECT) featuring self-assembled three-dimensional (3D) nanofiber arrays (NFAs) of small-molecule semiconductors grown on poly(3,4-ethylenedioxythiophene):polystyrenesulfonate active-layer channels. The hybrid OECT was further evaluated for its potential to capture, recover, and biosense circulating tumor cells (CTCs), as well as to enhance extracellular vesicle (EV) secretion through electrical stimulation (ES). Using template-free self-assembly via standard thermal evaporation, out-of-plane coronene (CR)-based NFAs were fabricated and surface-engineered with 1-pyrenebutyric acid through π-π interactions, enabling bioaffinity coatings on OECTs for advanced biological applications. The device demonstrated efficient CTC isolation, achieving an isolation rate exceeding 90% for MCF-7 breast cancer cells spiked into THP-1 monocytic cells (10 cells mL), with minimal nonspecific binding by incorporating a specific antibody-coated CR-based NFA layer. Moreover, over 80% of the captured CTCs were released from CR-based NFAs during cyclic voltammetry sweeps in phosphate-buffered saline. The device also enhanced EV secretion by incorporating a collagen-coated CR-based NFA layer, which supported cell attachment and proliferation under sustained ES at 20 V, 0.5 Hz, with 5 ms pulses for 24-72 h periods. EV production increased by approximately 12.4-fold in MCF-7 cells and 8.0-fold in immortalized bone marrow stromal cells without significantly altering the EV size or requiring additional cellular modifications. This dual-functionality platform, enabled by a surface-engineered 3D-hybrid OECT, is a powerful tool for selective CTC isolation, liquid biopsy purification, and enhanced EV production. This versatility highlights the potential of this approach for advanced bioelectronic applications and paves the way for innovations in diagnostics and therapeutic research.