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Abstract :
[en] Surface-Enhanced Raman Scattering (SERS) nanotags are highly attractive for bioanalytical applications due to their outstanding spectral selectivity and sensitivity. Strong SERS enhancement relies on the formation of intense electromagnetic hot spots, typically generated between closely spaced plasmonic nanoparticles. In this context, the controlled assembly of nanoparticle aggregates represents an efficient strategy to maximize SERS performance.
We report a continuous-flow chemistry approach enabling the controlled synthesis of gold nano-aggregates optimized for near-infrared (NIR) SERS. A two-stage microreactor platform was employed to induce aggregation of 30 nm gold nanoparticles using malachite green isothiocyanate (MGITC), simultaneously acting as Raman reporter and aggregating agent. Aggregation was subsequently quenched by introducing HS-PEG-COOH or HS-PEG-folic acid (FA), ensuring rapid stabilization of the nano-aggregates. Aggregation degree could be precisely adjusted by systematically tuning MGITC flow rate and residence time within the reactor. The resulting nano-aggregates were characterized using UV–Vis spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), and SERS. The flow-based platform further demonstrated excellent reversibility, allowing real-time switching between different aggregation states during operation. Optimized nano-aggregates exhibited a 100-fold increase in SERS sensitivity compared to non-aggregated nanoparticles. Moreover, functionalization with HS-PEG-FA provided targeting capabilities toward cancer cells overexpressing folate receptors3. In cancer tissue imaging performed under 785 nm excitation, nano-aggregates produced high-contrast SERS maps, whereas conventional non-aggregated SERS tags failed to generate detectable signals.
This work introduces an on-demand, continuous-flow strategy for producing tailored SERS nanotags that combine enhanced signal intensity with biological specificity, offering strong potential for biomedical imaging and diagnostic applications.
