Ultra-biocompatible PEDOT:DSS-modified dual-mode bi-directional microelectrode arrays reveal phase-locking dynamics across sleep-wake

Abstract

Long-term dynamic monitoring of cellular-level neural activity through implantable electrodes holds significant importance for elucidating sleep-wake regulation mechanisms. Nevertheless, the concerning biocompatibility, transient stability, and limited conductivity of conventional electrodes pose substantial challenges for high-quality signal acquisition. This study proposes a method for rapidly electrodepositing ultra-biocompatible poly(3,4-ethylenedioxythiophene):(dextran sulfate) (PEDOT:DSS) on conductive substrates to fabricate dual-mode bi-directional microelectrode arrays (MEAs). PEDOT:DSS utilizes the anionic polysaccharide dextran sulfate as the counterion template, which substantially enhances the biocompatibility of the PEDOT-based conductive polymer compared to conventional poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) coatings. Furthermore, increased surface roughness endows PEDOT:DSS-modified MEAs with superior conductivity (12.56 kΩ at 1 kHz), 2.89-fold higher charge storage capacity and enhanced electrochemical activity. Cyclic voltammetry aging and 1-h ultrasonic treatment demonstrate exceptional stability. During in vivo recordings over seven days, PEDOT:DSS electrodes exhibited only a 23.89 % noise increase and ∼2.52 % signal-to-noise ratio reduction, versus 74.51 % and 29.51 % for PEDOT:PSS. More importantly, multiple sleep-wake correlated neurons are identified showing stage-dependent firing rate variations, providing electrophysiological evidence for neuronal heterogeneity within these nuclei. Beyond firing rates, sleep-stage-specific delta-phase preference is unveiled for the first time. Certain neurons exhibit phase-locking only during wake, suggesting potential regulatory roles through location-specific firing patterns. This work establishes a high-performance electrode-neural interface, deciphers distinct neural activity patterns across sleep-wake stages, and substantially advances the development of implantable electrodes for neuroscientific research and clinical applications.