Nanoassembled SERS Sensing for Complex Biological Systems: From Hotspot Engineering to Interface Regulation

Area of Science:

• Plasmonics and Nanotechnology
• Vibrational Spectroscopy
• Biomedical Sensing

Background:

• Surface-enhanced Raman scattering (SERS) offers single-molecule sensitivity but struggles with complex biological environments due to interface challenges.
• Current SERS substrates often focus on hotspot engineering, neglecting analyte transport, capture, and signal stability.
• Effective SERS analysis requires a predictive understanding and rational control of analyte-hotspot interactions.

Purpose of the Study:

• To present a conceptual shift in SERS substrate design from passive hotspot engineering to active interface regulation.
• To establish a unified framework for SERS sensing in diverse biological systems (gas, liquid, solid-state).
• To overcome limitations in analyte transport, matrix interference, and signal stability in practical SERS applications.

Main Methods:

• Developed scalable, robust SERS substrates using precision nanoscale self-assembly and patterned printing ('printing assembly').
• Implemented aerodynamic modulation (pore confinement, cavity enrichment) for gas-phase SERS.
• Applied hydrodynamic manipulation (convective channels, filtration, wettability) for liquid-phase SERS.
• Utilized dielectric-mediated field extension for large-volume or noncontact targets.

Main Results:

• Achieved highly ordered, reproducible plasmonic superlattice substrates with uniform hotspots and mechanical robustness.
• Demonstrated enhanced analyte retention and transport efficiency in gas and liquid phases through tailored interfacial strategies.
• Extended detection limits beyond conventional near-field decay using dielectric-mediated field extension.
• Showcased that interface regulation is crucial for SERS performance, on par with hotspot engineering.

Conclusions:

• Active interface regulation, combined with hotspot engineering, provides a unified framework for robust SERS sensing in complex biological systems.
• Printing assembly offers a scalable pathway for fabricating high-performance SERS substrates.
• Future SERS development will benefit from AI integration for inverse design and spectral interpretation, accelerating its transition to a reliable analytical technology.