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Frequency Shift Surface-Enhanced Raman Spectroscopy Sensing: An Ultrasensitive Multiplex Assay for Biomarkers in Human Health

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  • Wenfeng Zhu, CAS - Institute of High Energy Physics, Chinese Academy of Medical Sciences, Peking Union Medical College
  • ,
  • James Andell Hutchison, University of Melbourne
  • ,
  • Mingdong Dong
  • Min Li, CAS - Institute of High Energy Physics

The sensitive and selective detection of biomarkers for human health remains one of the grand challenges of the analytical sciences. Compared to established methods (colorimetric, (chemi) luminescent), surface-enhanced Raman spectroscopy (SERS) is an emerging alternative with enormous potential for ultrasensitive biological detection. Indeed even attomolar (10-18 M) detection limits are possible for SERS due to an orders-of-magnitude boosting of Raman signals at the surface of metallic nanostructures by surface plasmons. However, challenges remain for SERS assays of large biomolecules, as the largest enhancements require the biomarker to enter a "hot spot"nanogap between metal nanostructures. The frequency-shift SERS method has gained popularity in recent years as an alternative assay that overcomes this drawback. It measures frequency shifts in intense SERS peaks of a Raman reporter during binding events on biomolecules (protein coupling, DNA hybridization, etc.) driven by mechanical transduction, charge transfer, or local electric field effects. As such, it retains the excellent multiplexing capability of SERS, with multiple analytes being identifiable by a spectral fingerprint in a single read-out. Meanwhile, like refractive index surface plasmon resonance methods, frequency-shift SERS measures the shift of an intense signal rather than resolving a peak above noise, easing spectroscopic resolution requirements. SERS frequency-shift assays have proved particularly suitable for sensing large, highly charged biomolecules that alter hydrogen-bonding networks upon specific binding. Herein we discuss the frequency-shift SERS method and promising applications in (multiplex) biomarker sensing as well as extensions to ion and gas sensing and much more.

Original languageEnglish
JournalACS Sensors
Pages (from-to)1704-1716
Number of pages13
Publication statusPublished - May 2021

    Research areas

  • bioassay, biomarker detection, early diagnosis, frequency-shift sensing, multiplex assay, surface plasmons, surface-enhanced Raman scattering (SERS), ultrasensitive detection, DIAGNOSIS, DESIGN, SILVER, NANOPARTICLES, TEMPERATURE, SERS, IMMUNOASSAY, STRESS, SCATTERING, SANDWICH ASSAY, Surface Plasmon Resonance, Humans, Luminescence, Nanostructures, Biomarkers, Spectrum Analysis, Raman

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