Customisable carbon–gold electrode architectures for point-of-care neurological biosensors

• Point-of-care diagnostic platforms for sensitive detection of neurological biomarkers. • Customisable carbon–gold screen-printed electrodes (SPCGEs) with integrated gold microflakes or microspheres. • Rapid electrode functionalisation enabled via gold–thiol chemistry, reducing fabrication time and enhancing reproducibility. • Gold microsphere-based electrodes exhibit superior electron transfer rates, higher surface area, and improved signal-to-noise ratios. • Scalable, low-cost carbon–gold inks enabling tuneable, multiplexed biosensors for diverse medical and environmental sensor applications. Biosensors for biomarkers associated with neurological diseases, such as blood miRNAs, can enable early detection and quantification thus improving treatment outcomes. Here, innovative and cost-effective point-of-care platforms are reported based on screen-printed carbon electrodes (SPCEs) with 10 (w/w)% of gold microflakes (L-AuF) or gold microspheres (L-AuS) integrated into a carbon ink. The incorporation of gold structures allows easy modification with thiol functional biorecognition molecules, reducing fabrication time and improving reproducibility. The electrochemical behaviour and analytical performance of both platforms were compared using chronoamperometry and cyclic voltammetry. Those incorporating AuS exhibit superior peak current values and a less negative potential for hydrogen peroxide reduction, reflecting a slightly higher rate of heterogeneous electron transfer (1.65±0.06×10 −4 cm s −1 vs. 1.21±0.04×10 −4 cm s −1 ) and a relatively higher surface area/number of biomolecule binding sites for the microsphere based electrodes. A fully complementary sandwich assay targeting miR-206, labelled using palladium nanocubes (PdNCBs) or commercially available gold nanorods (AuNRDs), as the probe strand label was developed. Assays utilizing PdNCBs on L-AuS SPCEs demonstrated a 10-fold current enhancement compared to those labelled with AuNRDs (SNR= 19.3 vs. 1.78). Similarly, L-AuF SPCEs with PdNCBs exhibited a 14-fold increase compared to the AuNRD-labelled assay on the same platform (SNR= 13.2 vs. 0.88). Irrespective of the nanoparticle used as the full assay label, SPCEs with integrated AuS consistently presented the best S/N ratio. Increasing the AuS loading in the ink resulted a 56-fold signal amplification, particularly when using AuNRDs as labels. These advanced inks hold promise for the future development of low-cost, multiplexed electrochemical biosensors targeting neurological diseases, offering design flexibility and potential for low limits of detection in point-of-care applications.