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Related Experiment Video

Updated: Apr 18, 2026

Label-Free Imaging of Lipid Storage Dynamics in Caenorhabditis elegans using Stimulated Raman Scattering Microscopy
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Label-free Imaging of Single-Biomolecule Structure and Interaction by Stimulated Raman Photothermal Encoded

Pin-Tian Lyu1,2, Yifan Zhu1,2, Qing Xia1,2

  • 1Department of Electrical and Computer Engineering, Boston University; Boston, MA 02215, USA.

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|April 17, 2026
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We developed stimulated Raman photothermal encoded scattering (SRPSCAT) microscopy for label-free, bond-selective imaging of single biomolecules. This technique provides quantitative structural and dynamic analysis of proteins in their native environments.

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Area of Science:

  • Biophysics
  • Chemical Imaging
  • Spectroscopy

Background:

  • Existing single-molecule techniques often rely on fluorescence or lack detailed chemical information.
  • There is a need for methods that can analyze biomolecular structure and interactions with chemical specificity at the single-molecule level.

Purpose of the Study:

  • To introduce and validate stimulated Raman photothermal encoded scattering (SRPSCAT) microscopy.
  • To demonstrate SRPSCAT's capability for quantitative, bond-selective imaging of single biomolecules in native environments.

Main Methods:

  • SRPSCAT microscopy combines stimulated Raman spectroscopy with interferometric scattering.
  • Vibrational spectroscopic information is encoded by modulating molecular scattering via stimulated Raman gain and loss processes.
  • Leverages single-molecule sensitivity for high-resolution imaging.

Main Results:

  • SRPSCAT enables mapping of single proteins with chemical specificity.
  • The method determines protein mass and distinguishes secondary structures using Raman fingerprints.
  • Quantifies single protein binding kinetics and observes conformational dynamics of allosteric proteins.

Conclusions:

  • SRPSCAT offers a powerful label-free approach for analyzing single biomolecules.
  • The technique provides structural, functional, and dynamic insights at the single-molecule level.
  • Highlights potential for advancing biophysical and biochemical research.