Covalent Linker-Functionalized Nanometer-Thick Gold Film Electrodes for Noninvasive Electrochemical C-Reactive Protein Detection

C-reactive protein (CRP) serves as a vital biomarker for the real-time monitoring of inflammation, infections, and cardiovascular diseases, offering critical insights into underlying health conditions. Despite its clinical significance, the lack of noninvasive point-of-care (POC) diagnostic tools has delayed timely detection and reduced patients’ compliance. Herein, a sensitive and selective electrochemical immunosensor is developed for the noninvasive detection of CRP, providing a painless and needle-free alternative to traditional diagnostics. The sensor is constructed using a thin-film deposition method, utilizing nanometer-thick gold electrodes functionalized with a covalent linker that simplifies antibody immobilization while enhancing the stability and specificity of the detection process. The immunosensor exhibited a linear detection range of 1–35 ng/mL and a lower detection limit of 0.27 ng/mL. The immunosensor exhibits higher reproducibility with a relative standard deviation of 1.12%. Stability studies validated its long-term performance with 90% retention of the initial response after 30 days. The practical real-time utility was evaluated by performing real sample analysis using both human and artificial sweat samples. The observed results highlighted the developed immunosensor ability to perform sensitive and selective detection of CRP noninvasively at point-of-care diagnostics for timely management of inflammatory and cardiovascular conditions.