Sensitive detection of both chemical contaminants and disease biomarkers is essential for food safety and biomedical analysis, yet existing analytical methods—such as chromatography and electrochemistry—rely on specialised instrumentation and remain costly when high sensitivity is required. Here, we report a morphology-engineered plasmonic sensing platform based on gold bipyramids (AuBPs), in which target-dependent modulation of tip-selective etching is converted into pronounced optical responses. In the presence of cetyltrimethylammonium bromide (CTAB) and Au3+, AuBPs undergo preferential etching at their sharp tips, producing substantial morphology-dependent blue shifts of the longitudinal surface plasmon resonance (LSPR) band. For tert-butylhydroquinone (TBHQ) detection, the reducing analyte competitively consumes Au3+ and thereby inhibits AuBP etching, resulting in concentration-dependent preservation of the bipyramidal morphology and shifts of the LSPR band towards longer wavelengths. The assay achieved detection limits of 0.09 μM by spectroscopy and approximately 0.5 μM by naked-eye observation, with its applicability further demonstrated through recovery analysis in spiked water samples. For biomarker sensing, AuBPs were integrated with an enzyme-linked immunosorbent assay for CD33, a biomarker associated with acute myeloid leukaemia. In this configuration, horseradish-peroxidase-generated oxidised TMB2+ acted as the etchant, producing CD33-dependent AuBP tip erosion and LSPR blue shifts over a linear range of 25–3000 pg/mL, with a detection limit of 9.2 pg/mL. Comparative experiments and finite-difference time-domain simulations showed that AuBPs exhibited substantially greater etching-induced optical responsiveness than gold nanorods and nanospheres, owing to their sharp tips and strongly localised electromagnetic fields. These findings establish a unified morphology-dependent, etching-modulated plasmonic framework for both direct small-molecule redox sensing and enzyme-mediated biomarker detection.
