Semiconductors have great potential as surface-enhanced Raman scattering (SERS) substrates due to their excellent physiochemical properties. However, they provide low signal enhancements relative to their plasmonic counterparts, which necessitates innovation in their synthesis and application. Substitutional atomic doping is proposed to improve SERS enhancement by controlling electronic properties, such as the band gap. In this work, zinc oxide (ZnO) nanoparticles were synthesized by co-precipitation and doped with magnesium (Mg) at concentrations ranging from 2–10%. Nanoparticle morphology and size were obtained by scanning electron microscopy (SEM). Elemental composition and chemical states were determined using X-ray photoelectron spectroscopy (XPS). Optical properties were obtained with a UV-vis spectrophotometer, while a Raman spectrometer was used to acquire Raman signal enhancements. Stability was assessed by UV-vis spectroscopy, while cytotoxicity was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results showed that the absorption edge of Mg-doped ZnO nanoparticles was red-shifted compared to pure ZnO nanoparticles. The band gap decreased (3.3–3.01 eV) with increasing Mg doping, while the highest Raman enhancement was observed at 2% doping. No significant cytotoxic effects were observed at low concentrations (3–12 μg/mL). Overall, this study provides evidence for the tunability of ZnO substrates and may serve as a platform for applications in molecular biosensing.

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.

Developing a biomolecular detection method that minimizes photodamage while maintaining 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 to enhance the signal of substrate materials are needed to improve reproducibility and costs associated with manu-facture and scale-up. Due to their physical properties and synthesis, semiconductor-based nanostructures have gained increasing recognition as SERS substrates; however, low signal en-hancements have offset their widespread adoption. To address this limitation and assess the po-tential for use in biological applications, zinc oxide (ZnO) was coated with different concentra-tions (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.