Deep Learning Assisted Surface-Enhanced Raman Spectroscopy (SERS) for Rapid and Direct Nucleic Acid Amplification and Detection: Toward Enhanced Molecular Diagnostics.

Journal: ACS nano
PMID:

Abstract

Surface-enhanced Raman scattering (SERS) has evolved into a robust analytical technique capable of detecting a variety of biomolecules despite challenges in securing a reliable Raman signal. Conventional SERS-based nucleic acid detection relies on hybridization assays, but reproducibility and signal strength issues have hindered research on directly amplifying nucleic acids on SERS surfaces. This study introduces a deep learning assisted ZnO-Au-SERS-based direct amplification (ZADA) system for rapid, sensitive molecular diagnostics. The system employs a SERS substrate fabricated by depositing gold on uniformly grown ZnO nanorods. These nanorods create hot spots for the amplification of the target nucleic acids directly on the SERS surface, eliminating the need for postamplification hybridization and Raman reporters. The limit of detection of the ZADA system was superior to those of the conventional amplification methods. Clinical validation of the ZADA system with coronavirus disease 2019 (COVID-19) samples from human patients yielded a sensitivity and specificity of 92.31% and 81.25%, respectively. The integration of a deep learning program further enhanced sensitivity and specificity to 100% and reduced SERS analysis time, showcasing the potential of the ZADA system for rapid, label-free disease diagnosis via direct nucleic acid amplification and detection within 20 min.

Authors

  • Myoung Gyu Kim
    Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei Ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
  • Miyeon Jue
    Biomedical Engineering Research Center, Asan Medical Center, Seoul 05505, Republic of Korea.
  • Kwan Hee Lee
    Department of Medical Science, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
  • Eun Yeong Lee
    Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei Ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
  • Yeonjeong Roh
    Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei Ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
  • Minju Lee
    Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei Ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
  • Hyo Joo Lee
    Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei Ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
  • Sanghwa Lee
    Biomedical Engineering Research Center, Asan Medical Center, Seoul 05505, Republic of Korea.
  • Huifang Liu
    Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei Ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
  • Bonhan Koo
    Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei Ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
  • Yoon Ok Jang
    Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei Ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
  • Eui Yeon Kim
    Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei Ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
  • Qiao Zhen
    Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei Ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
  • Sung-Han Kim
    Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
  • Jun Ki Kim
    Biomedical Engineering Research Center, Asan Medical Center, Seoul 05505, Republic of Korea.
  • Yong Shin
    Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei Ro, Seodaemun-gu, Seoul 03722, Republic of Korea.