NIH grant: Plasmonic Enhanced Raman Structured Illumination Microscopy (1R01GM163139-01)

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NIH grant 1R01GM163139-01: Plasmonic Enhanced Raman Structured Illumination Microscopy
Institute: {'code': 'GM', 'abbreviation': 'NIGMS', 'name': 'National Institute of General Medical Sciences', 'admin_org_id': '12500024', 'admin_funding_url': ''}. PI: Zhaowei  Liu. Award: $1830401.
Start: 2026-07-01T00:00:00.
PROJECT SUMMARY
This project aims to develop a novel microscopy technique known as Plasmonic Enhanced
Raman Structured Illumination Microscopy (PERSIM) to enhance the resolution and sensitivity of
Raman scattering microscopy (RSM). RSM is a valuable tool for label-free imaging as it can unveil
molecular characteristics based on their vibrational fingerprints. However, conventional Raman
scattering microscopy (RSM) instruments are limited by a spatial resolution of approximately 200
nm, primarily due to the diffraction limit, and they also suffer from low signal strength due to the
small Raman scattering cross-section.
PERSIM combines the strengths of Localized Plasmonic Structured Illumination Microscopy
(LPSIM) and RSM to produce label-free images with a resolution ~50 nm, representing a fourfold
improvement over standard RSM. The key innovation behind PERSIM lies in the utilization of
plasmonic nanoantennas array (PNA), capable of supporting localized surface plasmon
resonance (LSPR). This proposed approach holds great promise for applications in the fields of
biomedical imaging and biochemistry, as it can provide higher-resolution label-free imaging with
enhanced intensity and sensitivity compared to existing RSM techniques.
The PI Liu is a new investigator to NIH but has extensive expertise in pioneering high-speed and
super-resolution imaging techniques, bio-photonics, and nanoscale light manipulation through
plasmonic structures.
This project comprises three primary objectives. In Aim 1, we will design and construct the
PERSIM system, utilizing a functional LPSIM fluorescence setup and a standard SRS system
from the Liu lab. Aim 2 focuses on the critical element of the PNA substrate, which must be
meticulously designed and fabricated to operate effectively within the designated wavelength
range of the PERSIM system. Aim 3 involves the development of a autonomous neural network
based ultrafast image reconstruction algrith for real-time imaing and the validation of the complete
PERSIM system using well-known nanoscale structures in neuronal cells. We will also make a
comprehensive comparison between PERSIM, standard stimulated Raman scattering (SRS) and
super-resolution fluorece imaging.
The significance of this research lies in the development of PERSIM, a groundbreaking label-free
super-resolution microscopy technique poised to revolutionize the field of bioimaging. With its
unprecedented spatial resolution and imaging speed, PERSIM has the potential to catalyze new
scientific breakthroughs in biology and the life sciences. It opens exciting opportunities for
research and applications across a wide range of disciplines.

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