Cerebrospinal fluid-induced stable and reproducible SERS sensing for various meningitis discrimination assisted with machine learning.

Journal: Biosensors & bioelectronics
PMID:

Abstract

Cerebrospinal fluid (CSF)-based pathogen or biochemical testing is the standard approach for clinical diagnosis of various meningitis. However, misdiagnosis and missed diagnosis always occur due to the shortages of unusual clinical manifestations and time-consuming shortcomings, low sensitivity, and poor specificity. Here, for the first time, we propose a simple and reliable CSF-induced SERS platform assisted with machine learning (ML) for the diagnosis and identification of various meningitis. Stable and reproducible SERS spectra are obtained within 30 s by simply mixing the colloidal silver nanoparticles (Ag NPs) with CSF sample, and the relative standard deviation of signal intensity is achieved as low as 2.1%. In contrast to conventional salt agglomeration agent-induced irreversible aggregation for achieving Raman enhancement, a homogeneous and dispersed colloidal solution is observed within 1 h for the mixture of Ag NPs/CSF (containing 110-140 mM chloride), contributing to excellent SERS stability and reproducibility. In addition, the interaction processes and potential enhancement mechanisms of different Ag colloids-based SERS detection induced by CSF sample or conventional NaCl agglomeration agents are studied in detail through in-situ UV-vis absorption spectra, SERS analysis, SEM and optical imaging. Finally, an ML-assisted meningitis classification model is established based on the spectral feature fusion of characteristic peaks and baseline. By using an optimized KNN algorithm, the classification accuracy of autoimmune encephalitis, novel cryptococcal meningitis, viral meningitis, or tuberculous meningitis could be reached 99%, while an accuracy value of 68.74% is achieved for baseline-corrected spectral data. The CSF-induced SERS detection has the potential to provide a new type of liquid biopsy approach in the fields of diagnosis and early detection of various cerebral ailments.

Authors

  • Yali Song
    Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
  • Dongjie Zhang
    College of Food Science, Heilongjiang Bayi Agricultural University, Daqing 163000, China.
  • Lin Shi
    Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Shatin, China.
  • Peirao Yan
    Center for Biomedical-photonics and Molecular Imaging, Advanced Diagnostic-Therapy Technology and Equipment Key Laboratory of Higher Education Institutions in Shaanxi Province, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, 710126, China; Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education & Xi'an Key Laboratory of Intelligent Sensing and Regulation of Trans-Scale Life Information, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, 710126, China.
  • Zixu Wang
    Laboratory of Veterinary Anatomy, College of Animal Medicine, China Agricultural University, Haidian, Beijing, 100193, People's Republic of China.
  • Shanying Deng
    Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
  • Si Chen
    Department of Pharmacy, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
  • Yuemei Chen
    Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
  • Nan Wang
    Department of Gastroenterology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
  • Qi Zeng
    Department of Electrical and Computer Engineering, University of British Columbia, Vancouver, BC, Canada.
  • Tingting Zeng
    Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China. Electronic address: zengtingting80@scu.edu.cn.
  • Xueli Chen
    College of Engineering, China Agricultural University (East Campus) Box 191 Beijing 100083 China xwhddd@163.com +86 10 62736778 +86 10 62736778.