Integrated Multimodal Enhanced Raman Spectroscopy (iMERS) Enables Live Single-Cell Multimolecular Profiling

Area of Science:

• Spectroscopy
• Biochemistry
• Cell Biology

Background:

• Single-cell analysis offers deep insights into cellular heterogeneity and metabolism.
• Label-free spectroscopic methods are crucial for small-molecule metabolomics but struggle with sensitivity.
• Existing techniques lack the precision for detailed molecular profiling of individual cells.

Purpose of the Study:

• To develop an advanced label-free spectroscopic method for sensitive, semiquantitative multimolecular profiling of single cells.
• To enhance the interpretation of intracellular and extracellular small-molecule metabolomics.
• To enable accurate molecular analysis for applications like cancer subtype identification.

Main Methods:

• Integrated multimodal enhanced Raman spectroscopy (iMERS) combining nanofabrication for surface-enhanced Raman scattering (SERS).
• Adaptive spectral signal recovery and quantitative regression algorithms using digitized Raman signatures.
• Proactive stimulation-assisted single-cell profiling for enhanced data acquisition.

Main Results:

• iMERS enables quantitative, label-free acquisition of cellular multimolecular information with high accuracy.
• The method demonstrates high time efficiency and cost-effectiveness in molecular profiling.
• Successfully applied iMERS to distinguish indistinguishable liver cancer subtypes with up to 81% accuracy.

Conclusions:

• The iMERS approach significantly enhances sensitivity and accuracy in single-cell multimolecular profiling.
• This label-free technique provides a powerful tool for metabolomics and cellular analysis.
• iMERS shows significant potential for precision clinical medicine and broader biological research.