Counterion-Engineered Redox-Active Lipid Cubic Phases for Stable Enzyme Bioelectrodes

Abstract The fabrication of stable and highly performing enzyme-based electrodes is key for the effective generation of biodevices and bioelectronics, such as electrochemical biosensors. In this context, redox-active lyotropic liquid crystals based on 3D nanomaterials, known as lipid cubic phases (LCP), hold great potential due to the large specific surface area and the possibility of being functionalized. In this study, we functionalized a monoolein (MO) LCP matrix by incorporating an amphiphilic redox shuttle within its matrix with the aim of enhancing the electrochemical performance of a glucose oxidase (GOx) based electrode, and we investigated the stability of the overall system. The use of dodecyl(ferrocenylmethyl)dimethylammonium bromide (Fc12-Br) resulted in a progressive attenuation of its redox response during repeated potential cycling, consistent with cycling-induced blocking potentially involving Br– electrosorption. To address this instability, counterion exchange from Br– to hexafluorophosphate (PF6–) yielded Fc12-PF6/MO. Both formulations were subsequently used to entrap GOx, and the resulting bioelectrodes were evaluated for their electrochemical responses to glucose. Although the initial glucose sensitivities of the Fc12-Br/MO/GOx and Fc12-PF6/MO/GOx systems were comparable, the latter showed improved retention of its amperometric response during storage, retaining 80% ± 5% of its initial response to 6 mM glucose at day 20 under the tested conditions. Together with the improved electrochemical reversibility of the Fc12-PF6/MO system under repeated redox cycling, these observations support counterion engineering as a promising strategy for improving the durability of redox-active lipid cubic phase bioelectrodes.