Enhancing the specificity of Raman spectroscopy by using multiple lasers

Raman spectroscopy is a powerful tool for molecular fingerprinting yet has been limited in clinical utility due to decrease in specificity when analyzing complex biological samples. Here we present MX-Raman, a multiexcitation Raman method that enhances molecular discrimination by fusing spectral data acquired with multiple laser wavelengths into a single, enhanced optical fingerprint. In this work, MX-Raman is applied to cerebrospinal fluid (CSF) samples from a heterogeneous dementia cohort, including Alzheimer’s disease (AD), frontotemporal dementia (FTD) spectrum disorders, and non-neurodegenerative cognitive conditions, to achieve improved clustering and disease stratification. Furthermore, we extend the MX-Raman approach to blood plasma, demonstrating potential for a rapid, label-free, and minimally invasive diagnostic test for dementia detection and stratification. Overall, MX-Raman offers a scalable, optical technology platform that underscores how photonic advancements can address real-world clinical challenges.