# Super-resolution Chemical Imaging for Biomedicine

> **NIH NIH DP2** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2020 · $2,331,856

## Abstract

Project Abstract
 Optical microscopy has revolutionized our understanding of biological systems with fine
subcellular resolution, fast temporal dynamics and superb target specificity. One of the recent
technical breakthroughs in bioimaging is the super-resolution fluorescence microscopy, which
breaks the diffraction limit and allows unprecedented optical investigation at the nanoscopic
level. However, super-resolution fluorescence microscopy has been fundamentally limited in two
aspects. First, it is not suitable for interrogating structures mainly composed of small
biomolecules, due to the required large and perturbative fluorophore labeling. Second, it is
ineffective for investigating small complex structures involving multiple components because the
broad and featureless fluorescent spectra limits the colors that could be simultaneously imaged
typically to only 2-5. Therefore, how to noninvasively super-resolve these two types of cellular
structures has remained as grand challenges in bioimaging.
 In this proposal, we aim to develop two Super-resolution Chemical Imaging techniques to
tackle these challenges by utilizing a single contrast mechanism, the Raman scattering, to study
the aforementioned less-explored directions of imaging small biomolecules and simultaneous
imaging a large number (>20) of targets in cells, respectively. To do so, we plan to bring the
most advanced and biocompatible Raman imaging modality, the stimulated Raman scattering
microscopy, into the super-resolution regime. We will first prove the working principles for the
designed spectroscopy and then demonstrate the microscopy methods. We aim to achieve a
resolution improvement of more than 3 times, thus pushing the achievable imaging resolution to
below 100 nm. This resolution range would be highly suited for interrogating the target biological
structures and the dynamics.
 If successfully developed, these two novel Super-resolution Chemical Imaging techniques
could be transformative and bring optical bioimaging to the next frontier for studying unresolved
biophysical and biochemical processes in the complex biological systems. All these
fundamental understandings would ultimately help researchers to elucidate the key functional
roles of these intricate structures in biomedical fields including neurobiology and cancer biology.

## Key facts

- **NIH application ID:** 10002909
- **Project number:** 1DP2GM140919-01
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Lu Wei
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,331,856
- **Award type:** 1
- **Project period:** 2020-09-30 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10002909

## Citation

> US National Institutes of Health, RePORTER application 10002909, Super-resolution Chemical Imaging for Biomedicine (1DP2GM140919-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10002909. Licensed CC0.

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