Ultrasonic spray pyrolysis and electro-nanofabrication of carbon-gold-based biosensor for circulating tumor cell detection.

The development of an ultrasensitive electrochemical biosensor for the label-free detection of HER2-positive breast cancer cells is reported. The developed platform leverages a novel hierarchical nanoarchitecture to achieve superior analytical performance. The nanofabricated system was constructed by depositing a carbon-gold nanoparticle (C-AuNP) layer on a fluorine-doped tin oxide (FTO) electrode via ultrasonic spray pyrolysis, in the first step. The process was followed by the electrochemical growth of gold nanostructures (AuNS) to form a conductive C-AuNP@AuNS nanocomposite. This tailored nanofabrication, dramatically enhanced the electrode's conductivity and provided an optimal substrate for bioreceptor immobilization. The surface was functionalized with Herceptin antibody for specific cell capture. Quantitative performance was evaluated using electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV). The biosensor demonstrated a wide linear response from 2.5 × 102 to 1 × 104 cells mL⁻¹, an exceptionally low limit of detection (LOD) of 2 cells mL⁻¹, and high specificity against HER2-negative MCF7 cells, confirming minimal non-specific adsorption. The sensor's robustness was validated by its stable biorecognition layer, which retained functionality for over three months. This work advances the field by integrating a scalable spray pyrolysis step with precise electrochemical nanostructuring to create a high-performance interface. The achieved metrics, combining an ultra-low LOD, and operational stability in complex media, represent a significant improvement over existing HER2 cell sensors. In addition, these results underscore the platform's strong potential for translation into early, point-of-care cancer diagnostics.