| Summary: | Developing a biomolecular detection method that minimizes photodamage while preserving an environment suitable for biological constituents to maintain their physiological state is expected to drive new diagnostic and mechanistic breakthroughs. In addition, ultra-sensitive diagnostic platforms are needed for rapid and point-of-care technologies for various diseases. Considering this, surface-enhanced Raman scattering (SERS) is proposed as a non-destructive and sensitive approach to address the limitations of fluorescence, electrochemical, and other optical detection techniques. However, to advance the applications of SERS, novel approaches that can enhance the signal of substrate materials are needed to improve reproducibility and costs associated with manufacture and scale-up. Due to their physical properties and synthesis, semiconductor-based nanostructures have gained increasing recognition as SERS substrates; however, low signal enhancements have offset their widespread adoption. To address this limitation and assess the potential for use in biological applications, zinc oxide (ZnO) was coated with different concentrations (0.01–0.1 M) of gold (Au) precursor. When crystal violet (CV) was used as a model target with the synthesized substrates, the highest enhancement was obtained with ZnO coated with 0.05 M Au precursor. This substrate was subsequently applied to differentiate exosomes derived from three cell types to provide insight into their molecular diversity. We anticipate this work will serve as a platform for colloidal hybrid SERS substrates in future bio-sensing applications.
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