Small Biomolecular Detection Based on Small-Signal Transconductance of Suspended Double-Network Hydrogels as Organic Electrochemical Transistors

Semiconducting double-network (DN) hydrogels are a promising materials platform for development of bioelectronics and biosensors, as the composite structure offers means for readily tailoring electrical, electrochemical, and importantly, mechanical properties to design device functions and improve biocompatibility. Previously, we demonstrated that DN hydrogels prepared by radical polymerization of acrylamide monomers in suspension with commercially sourced PEDOT:PSS (poly(3,4-ethylenedioxythiophene) complexed with poly(styrenesulfonate)) solutions are able to maintain the good electrical transport properties of PEDOT despite compositions of ~70% water by volume [1]. By incorporating phenylboronic acid (PBA) moieties in the polyacrylamide network, selective binding sites for biomolecules bearing vicinal diols (e.g., glucose or dopamine) were prepared. To obtain an electrochemical and non-enzymatic response to biomolecule concentration, we couple the PBA binding equilibrium with an electrocatalyzed peroxo pathway for O₂ reduction (ORR) on cathodically polarized PEDOT [2]. As the response signal does not require the target to be consumed, this detection scheme avoids the oxidizing conditions which may give rise to confounding signals from common interferents in biological assays (e.g. antioxidant species).<br/>Simultaneously, increasing channel thickness and reduced volumetric capacitance in composite hydrogels motivates a shift towards application as a transducer with built-in amplification rather than as a typical ionic amplifier of Faradaic currents flowing from a sensitized gate electrode. By leveraging the mechanical strength of hydrogels, we fabricate organic electrochemical transistors (OECTs) with suspended channels on flexible polyimide substrates that enable 3D access for mass transport of analyte biomolecules and ions drifted by applied potentials. Accordingly, this configuration improves the OECT bandwidth by about two-fold thanks to a reduction in effective thickness. In conjunction with the use of a traditional reference/counter electrode pair, this enables the poising of small-signal (AC) transconductance measurements (via DC gate potential, AC amplitude and frequency) to directly probe at the rate of ORR with changes in PBA equilibrium. That is, the current of electrons supplied at the OECT drain for the regeneration of PEDOT catalyst is directly measured at a characteristic frequency for ORR. The resulting signal achieves sub-millimolar sensitivity for glucose in phosphate buffer, which is promising for non-invasive monitoring application.<br/><br/>[1] A. C. Tseng <i>et al.</i>, <i>ACS Appl. Mater. Interfaces</i>, vol. 14, no. 21, pp. 24729–24740, Jun. 2022.<br/>[2] E. Mitraka <i>et al.</i>, <i>Advanced Sustainable Systems</i>, vol. 3, no. 2, p. 1800110, Feb. 2019.