pH-Adjusted Liquid SERS Approach: Toward a Reliable Plasma-Based Early Stage Lung Cancer Detection

Surface-enhanced Raman spectroscopy (SERS) provides a rapid and nondestructive method for biological plasma analysis, offering unparalleled sensitivity and specificity. However, most current studies predominantly employ the drop-cast method, where liquid samples are dried on the SERS substrate for spectral recording. While effective, this method is both time-consuming and inconsistent. Additionally, the Raman spectral signal of uric acid in plasma often dominates, overshadowing other crucial biomarkers necessary for disease differentiation. In this study, we present the application of label-free SERS detection for distinguishing early stage lung cancer (LC) from healthy controls (HC) using plasma samples. Plasma was diluted, adjusted to a weakly acidic pH, and combined with silver nanoparticles (Ag NPs) for SERS analysis. To maintain the plasma in a liquid state and prevent evaporation, liquid paraffin was employed. Our findings indicate that a 10-fold dilution of plasma under weakly acidic conditions significantly enhanced diagnostic performance, achieving an area under the receiver operating characteristic curve (AUC) of 0.975. This method is featured by its simplicity and high efficiency, presenting a promising strategy for the minimally invasive diagnosis of early stage LC using SERS technology.