Noncontact Mode Surface-Enhanced Raman Spectroscopy Analysis Empowered by Molecular-Scaffold-Gifting Au Nanochannel

Area of Science:

• Analytical Chemistry
• Spectroscopy
• Materials Science

Background:

• Label-free quantitative detection is crucial for medical diagnostics, food safety, and law enforcement.
• Surface-Enhanced Raman Spectroscopy (SERS) offers sensitive molecular identification but suffers from reproducibility issues in conventional contact modes.
• Random analyte orientation and competitive binding on bare metal surfaces limit SERS reliability.

Purpose of the Study:

• To develop a noncontact SERS platform for reproducible and quantitative molecular detection.
• To overcome the limitations of conventional contact-mode SERS regarding signal heterogeneity and reproducibility.
• To demonstrate the platform's capability in discriminating enantiomers and analyzing complex samples.

Main Methods:

• Utilized fluorenylmethoxycarbonyl-lysine (Fmoc-Lys) scaffolds within nanoporous gold nanospheres (1-2 nm channels).
• Employed a noncontact SERS mode where Fmoc core captures analytes via hydrophobic interactions, with chiral centers regulating adsorption.
• Fixed analyte distance and orientation relative to the plasmonic hotspots to minimize spectral variation.

Main Results:

• Achieved reproducible and predictable SERS spectra readout.
• Demonstrated discrimination of subtle enantiomeric differences.
• Successfully quantified methamphetamine (METH) in human urine samples with accuracy comparable to mass spectrometry, without needing analyte-specific reference spectra.

Conclusions:

• Noncontact SERS using Fmoc-Lys scaffolds offers a general strategy for reliable and ultrasensitive molecular analysis.
• This platform is particularly advantageous for analyzing targets lacking standard spectral libraries.
• The approach minimizes stochastic spectral variation, enhancing quantitative accuracy and reproducibility.