Cell separation coupled with surface-enhanced Raman spectroscopy: A critical review

Area of Science:

• Biomedical Engineering
• Analytical Chemistry
• Spectroscopy

Background:

• Sensitive molecular diagnostics are crucial for disease detection and environmental monitoring.
• Surface-enhanced Raman spectroscopy (SERS) offers high sensitivity for molecular detection.
• Cell separation technologies are essential for isolating target analytes from complex samples.

Purpose of the Study:

• To critically review cell separation technologies integrated with SERS for diagnostic applications.
• To evaluate both label-dependent and label-free separation methods.
• To identify challenges and future prospects for SERS-based diagnostic platforms.

Main Methods:

• Review of label-dependent (FACS, MACS) and label-free (DEP, acoustic, magnetic, inertial, DLD) cell separation techniques.
• Analysis of on-chip and off-chip integration strategies for SERS detection.
• Examination of hybrid cascaded architectures combining multiple separation mechanisms.

Main Results:

• Integration of cell separation with SERS enhances sensitivity for molecular diagnostics.
• On-chip integration enables continuous operation and real-time monitoring.
• Hybrid architectures achieve high throughput and specificity, addressing key challenges like standardization and stability.

Conclusions:

• Cell separation coupled with SERS presents a powerful platform for cancer diagnosis, pathogen detection, and environmental monitoring.
• Machine learning and portable spectrometers are key to advancing SERS diagnostics towards point-of-care settings.
• Further research is needed for robust, reproducible, and clinically validated SERS-based diagnostic systems.