Chemical and physical control of biointerfaces is attractive because of its flexibility and effectiveness in cell and tissue regulation, as well as in diagnostic and therapeutic applications.[1–7] When introducing biochemical cues to cells, various cell activities (eg, adhesion, spreading morphologies, proliferation) can be manipulated at their biointerfaces.[5–7] For example, in the development of stem cell therapies, surfaces modified with synthetic peptides can be used to support the self-renewal and differentiation of stem cells.[4] Notably, specific cell–substrate interactions observed on three-dimensional (3D) micro/nanostructures can provide the topographic cues regulating the cell spreading morphology of neurons,[8, 9] thereby promoting the level of cell differentiation for stem cells,[10–12] enhancing the transfection efficiency of cells with targeted gene expression,[13–15] and improving the capturing efficiency of circulating tumor cells (CTCs) for noninvasive blood biopsies.[16–21] In addition to these biological applications, integrating additional electrical functionality into biointerfaces has recently attracted significant interest for the digital transformation of biological signals within bioelectronics.[22, 23]

Bioelectronic interfaces (BEIs) are promising intermediate layers that can enhance communication between electronics and biological systems; they can be operated to couple the flows of electrons and ions in dual directions. Accordingly, BEIs have great potential for use in electrical signaling,[22, 23] stimulation,[24–28] and electrically triggered-response toward the release and pumping of small molecules.[29–33] In the development of BEIs, organic conducting polymers [CPs; eg, polypyrrole or poly (3, 4-ethylenedioxythiophene)(PEDOT)] have been applied widely for their outstanding electrical transport properties, inherent biocompatibility, and high manufacturing flexibility. Indeed, CPs can be synthesized with a diverse array of chemical designs, such as the incorporation of various anionic dopants [eg, poly (sodium styrene sulfonate)(PSS), tosylate (TOS)][34–36] and/or the presenting of various functional side chains,[20, 37–39] thereby extending their applicability. For instance, TOS-doped PEDOT (PEDOT: TOS) materials are currently the most promising BEIs because of their high electrical stability and biocompatibility, allowing long-term cell culturing or implantation;[36] alternatively, carboxylic acid–grafted PEDOT (PEDOTAc) materials can be conjugated to a specific cell capturing agent for CTC assays.[20] Briefly, this bioconjugation process involves initial activation of the carboxylic acid groups, using N-hydroxysuccinimide (NHS) and 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride (EDC), and subsequent conjugation with streptavidin. The streptavidin-grafted PEDOT films are then incubated with biotinylated anti-EpCAM to