Related Experiment Video
Updated: Jun 15, 2025

In vivo Imaging of Biological Tissues with Combined Two-Photon Fluorescence and Stimulated Raman Scattering Microscopy
Published on: December 20, 2021
Self-stacked small molecules for ultrasensitive, substrate-free Raman imaging in vivo.
Shuai Gao1, Yongming Zhang2, Kai Cui2
1School of Pharmacy & Minhang Hospital, State Key Laboratory of Molecular Engineering of Polymers, Key Laboratory of Smart Drug Delivery Ministry of Education, Fudan University, Shanghai, China.
A novel stacking-induced charge transfer-enhanced Raman scattering (SICTERS) technique uses self-stacking molecules for ultrasensitive in vivo imaging. This substrate-free approach overcomes biosafety concerns associated with traditional surface-enhanced Raman scattering (SERS) probes.
Area of Science:
- Biomedical Optics
- Materials Science
- Spectroscopy
Background:
- Surface-enhanced Raman scattering (SERS) nanoprobes offer ultrasensitive in vivo imaging.
- Clinical application of SERS is limited by biosafety concerns regarding metal substrates.
Purpose of the Study:
- To develop a substrate-free Raman scattering enhancement technique for improved in vivo imaging.
- To address biosafety limitations of current SERS nanoprobes.
Main Methods:
- Developed small molecules with bis-thienyl-substituted benzobisthiadiazole structures.
- Utilized stacking-induced charge transfer-enhanced Raman scattering (SICTERS) where self-stacked molecules enhance Raman signals.
- Compared SICTERS nanoprobes with conventional SERS gold nanoprobes.
Main Results:
- SICTERS nanoprobes exhibited a 1350-fold higher Raman scattering cross-section than SERS nanoprobes.
- SICTERS demonstrated superior in vivo imaging sensitivity, resolution, and depth compared to SERS.
- Achieved noninvasive Raman imaging of blood and lymphatic vasculatures, a feat not possible with SERS.
Conclusions:
- SICTERS is a promising substrate-free alternative for Raman scattering enhancement.
- This technique offers enhanced performance and improved biosafety for in vivo imaging applications.
- SICTERS provides a new paradigm for designing ultrasensitive Raman imaging probes.

