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

Abstract

Single-cell multimolecular profiling provides a holistic understanding of cellular heterogeneity and metabolic mechanisms. A label-free spectroscopic approach is expected to advance multimolecular analysis, particularly for the interpretation of small-molecule metabolomics, but faces a great challenge in terms of poor sensitivity. Here, we propose an integrated multimodal enhanced Raman spectroscopy (iMERS) method for the semiquantitative molecular profiling of intracellular and extracellular molecules of single cells. The iMERS method involves a cost-effective and well-controllable nanofabrication for surface-enhanced Raman scattering (SERS), an adaptive spectral signal recovery and a quantitative regression algorithm based on digitized Raman signature, and a proactive stimulation-assisted single-cell profiling. Through the iMERS approach, cellular multimolecular information can be quantitatively acquired from the label-free spectra with high accuracy, high time efficiency, and cost-efficiency. We apply iMERS to recognize indistinguishable liver cancer subtypes, achieving an accuracy of up to 81%. The iMERS approach has promising potential for broad applications in single-cell multimolecular analysis, precision clinical medicine, etc.