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Frequency Shift Raman-Based Sensing of Serum MicroRNAs for Early Diagnosis and Discrimination of Primary Liver Cancers Wenfeng Zhu, Linxiu Cheng, Min Li, Duo Zuo, Ning Zhang, Hongjun Zhuang, Dan Xie, Qingdao Zeng, James A. Hutchison, and Yuliang Zhao Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.8b01798 • Publication Date (Web): 05 Jul 2018 Downloaded from http://pubs.acs.org on July 5, 2018
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Analytical Chemistry
Frequency Shift Raman-Based Sensing of Serum MicroRNAs for Early Diagnosis and Discrimination of Primary Liver Cancers Wen-Feng Zhu†, Lin-Xiu Cheng†, ‡, ‖, Min Li†,*, Duo Zuo‖, Ning Zhang‖, Hong-Jun Zhuang†, Dan Xie†, Qing-Dao Zeng‡, James A HutchisonΔ,*, Yu-Liang Zhao†, ‡, * † CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, 19B Yuquan Road, Shijingshan District, Beijing 100049, China. ‡ CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China. ‖Department of Cancer Cell Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China. Δ School of Chemistry and Bio21 Institute, University of Melbourne, 30 Flemington Rd, Parkville Victoria, 3052 Australia. ∏ University of the Chinese Academy of Sciences, 19A Yuquan Road, Shijingshan District, Beijing 100049, P. R. China. Corresponding Author: *E-mail:
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ABSTRACT: Frequency shift surface-enhanced Raman scattering (SERS) achieves multiplex microRNA sensing for early serological diagnosis of, and discrimination between, primary liver cancers in a patient cohort for whom only biopsy is effective clinically. Raman reporters micro-printed on plasmonic substrates shift their vibrational frequencies upon biomarker binding with a dynamic range allowing direct, multiplex assay of serum microRNAs and the current best protein biomarker, α-fetoprotein. Benchmarking against current gold-standard polymerase chain reaction and chemiluminescence methods validates the assay. The work further establishes the frequency shift approach, sensing shifts in an intense SERS band, as a viable alternative to conventional SERS sensing which involves the more difficult task of resolving a peak above noise at ultra-low analyte concentrations.
Liver cancer kills >700,000 people every year with nearunity mortality-to-incidence ratio.1 Incidence is low but rising in western countries, and concentrated in East Asia with over half of cases occurring in China.2 Liver cancer is the primary cause of cancer-related deaths for East Asians of working age (
