Nanostructured Gold Platforms for Attogram-Precision Cardiolipin Quantification

Abstract

An ultra-sensitive electrochemical immunosensor is presented for the precise quantification of cardiolipin, a key biomarker of mitochondrial dysfunction and cardiovascular pathologies. This innovative platform utilizes two distinct gold nanostructures, nanorods and nanodendrites, within the sensing electrode to achieve exceptional sensitivity and selectivity. These nanostructures were synthesized through a sequential process involving physical vapor deposition of an ultrathin gold film, thermal annealing to nucleate gold seeds, and precision electrochemical deposition, enabling controlled growth on fluorine-doped tin oxide (FTO) substrates. This template-free strategy, optimized through systematic parameter refinement, ensures high reproducibility and electrochemical efficiency. Unlike conventional colloidal synthesis methods that rely on seed-mediated growth and extensive surfactant usage, our template-free electrochemical approach offers a simpler, more reproducible, and surfactant-reduced route for fabricating well-controlled gold nanostructures suitable for biocompatible sensing platforms. Morphological, structural, and surface characterizations of the nanostructures were performed using field emission scanning electron microscopy, X-ray diffraction, and contact angle measurements, confirming well-defined growth and controlled surface wettability. Electrochemical analyses, including cyclic voltammetry and electrochemical impedance spectroscopy, further revealed enhanced electron transfer and reduced interfacial resistance, verifying their suitability for sensitive biosensing applications. Functionalization with anti-cardiolipin antibodies ensures high specificity. Electrochemical measurements reveal a dynamic linear range (1 ag/mL to 0.1 pg/mL) and detection limits of 0.19 ag/mL (nanorods) and 0.51 ag/mL (nanodendrites). Nanorods demonstrate superior charge transfer, lower impedance, and greater accessibility, positioning this scalable platform as a paradigm shift for lipidomic profiling and advanced diagnostics in precision medicine.