Forward-predictive SERS-based chemical taxonomy for untargeted structural elucidation of epimeric cerebrosides

• Main Authors: Tan, Emily Xi, Leong, Shi Xuan, Liew, Wei An, Phang, In Yee, Ng, Jie Ying, Tan, Nguan Soon, Lee, Yie Hou, Ling, Xing Yi
• Other Authors: School of Chemistry, Chemical Engineering and Biotechnology
• Format: Article
• Language: English
• Published: 2024
• Subjects: Medicine, Health and Life Sciences; Chemical fingerprinting; Hydrophobicity
• Online Access: https://hdl.handle.net/10356/174716
• Institution: Nanyang Technological University

Achieving untargeted chemical identification, isomeric differentiation, and quantification is critical to most scientific and technological problems but remains challenging. Here, we demonstrate an integrated SERS-based chemical taxonomy machine learning framework for untargeted structural elucidation of 11 epimeric cerebrosides, attaining >90% accuracy and robust single epimer and multiplex quantification with <10% errors. First, we utilize 4-mercaptophenylboronic acid to selectively capture the epimers at molecular sites of isomerism to form epimer-specific SERS fingerprints. Corroborating with in-silico experiments, we establish five spectral features, each corresponding to a structural characteristic: (1) presence/absence of epimers, (2) monosaccharide/cerebroside, (3) saturated/unsaturated cerebroside, (4) glucosyl/galactosyl, and (5) GlcCer or GalCer's carbon chain lengths. Leveraging these insights, we create a fully generalizable framework to identify and quantify cerebrosides at concentrations between 10-4 to 10-10 M and achieve multiplex quantification of binary mixtures containing biomarkers GlcCer24:1, and GalCer24:1 using their untrained spectra in the models.