Single-Molecule SERS Detection of Phosphorylation in Serine and Tyrosine Using Deep Learning-Assisted Plasmonic Nanopore.

Journal: The journal of physical chemistry letters
Published Date: Aug 8, 2025

Abstract

Single-molecule detection of post-translational modifications (PTMs) such as phosphorylation plays a crucial role in early diagnosis of diseases and therapeutics development. Although single-molecule surface-enhanced Raman spectroscopy (SM-SERS) detection of PTMs has been demonstrated, the data analysis and detection accurracies were hindered by interference from citrate signals and lack of reference databases. Previous reports required complete coverage of the nanoparticle surface by analyte molecules to replace citrates, hampering the detection limit. Here, we developed a high-accuracy SM-SERS approach by combining a plasmonic particle-in-pore sensor to collect SM-SERS spectra of phosphorylation at Serine and Tyrosine, k-means-based clustering for citrate signal removal, and a one-dimensional convolutional neural network (1D-CNN) for phosphorylation identification. Significantly, we collected SM-SERS data with submonolayer analyte coverage of the particle surface and discriminated the phosphorylation in Serine and Tyrosine with over 95% and 97% accuracy, respectively. Finally, the 1D-CNN features were interpreted by a one-dimensional gradient feature weight and SM-SERS peak occurrence frequencies.

Authors

  • Mulusew W Yaltaye
    Research Unit of Health Sciences and Technology, Faculty of Medicine, University of Oulu, Aapistie 5 A, 90220 Oulu, Finland.
  • Yingqi Zhao
    Public Health Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Kuo Zhan
    Research Unit of Health Sciences and Technology, Faculty of Medicine, University of Oulu, Aapistie 5 A, 90220 Oulu, Finland.
  • Eva Bozo
    Research Unit of Health Sciences and Technology, Faculty of Medicine, University of Oulu, Aapistie 5 A, 90220 Oulu, Finland.
  • Pei-Lin Xin
    Key Laboratory for Advanced Materials, Shanghai Key Laboratory of Functional Materials Chemistry, Frontiers Science Center for Materiobiology & Dynamic Chemistry, School of Chemistry & Molecular Engineering, East China University of Science and Technology, Shanghai 200237, P. R. China.
  • Vahid Farrahi
    Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland. Electronic address: Vahid.farrahi@oulu.fi.
  • Francesco De Angelis
    Istituto Italiano di Tecnologia, via Morego 30, 16163 Genova, Italy.
  • Jian-An Huang
    Research Unit of Health Sciences and Technology (HST), Faculty of Medicine University of Oulu, Oulu, 999018, Finland.

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