Quantitative Surface-Enhanced Raman Spectroscopy: Challenges, Strategies, and Prospects.

Area of Science:

• Analytical Chemistry
• Spectroscopy

Background:

• Surface-Enhanced Raman Spectroscopy (SERS) provides high sensitivity, molecular specificity, and speed.
• It has potential for affordable, portable applications like bedside diagnostics and forensic analysis.
• SERS remains specialized due to challenges in achieving robust, quantitative measurements.

Purpose of the Study:

• To summarize challenges in quantitative SERS measurements.
• To detail modern strategies for improving SERS reliability and quantification.
• To explore future prospects for integrating SERS into routine analytical practice.

Main Methods:

• Review of fundamental challenges in signal variability and matrix interference.
• Discussion of strategies for standardizing performance metrics, including the SERS Performance Factor.
• Exploration of advanced quantification methods (internal standardization, digital SERS) and sample pretreatment.

Main Results:

• Identified signal variability and matrix interference as key hurdles for quantitative SERS.
• Highlighted the importance of standardized performance metrics and novel quantification approaches.
• Emphasized the potential of AI and deep-tissue sensing for SERS advancement.

Conclusions:

• Addressing substrate heterogeneity and sample complexity is crucial for quantitative SERS.
• Standardization, advanced quantification, and AI are key to overcoming current limitations.
• SERS is poised for broader adoption in analytical chemistry with further development.