# High-resolution spectroscopic imaging with infrared nonlinear optical (IR-NLO) microscopy

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $135,129

## Abstract

Project Summary
A genuine label-free imaging technology, vibrational microscopy provides maps of cells and tissues
with exceptionally high chemical contrast as it directly probes the fundamental vibrational modes of
samples. Vibrational imaging approaches include IR-absorption micro-spectroscopy and confocal
Raman microscopy, methods that have been successfully commercialized (a growing 500 million
dollar market) and are now common tools of inquiry found in analytical and biological laboratories.
Over the past four decades, these techniques have had a measurable impact in the fields of biology
and biomedicine, offering a spatially resolved assessment of healthy and diseased tissues from a
molecular perspective. This proposal aims to significantly improve the capabilities of vibrational
microscopy. We propose a new imaging approach that merges the desirable properties of IR
absorption microscopy with some of the unique properties of coherent, nonlinear optical (NLO)
excitation of molecules. This novel IR-NLO technique improves the spatial resolution of IR absorption
microscopy by tenfold, while offering higher sensitivity to fingerprint molecular vibrations relative to
Raman-based microscopy methods.
Our team is comprised of experts in coherent Raman scattering microscopy and IR
microspectroscopic imaging. Our innovation makes it possible to rapidly acquire IR absorption images
of fingerprint vibrational modes with a resolution of 0.5 micrometer or better. The preliminary data
shows that the IR-NLO approach can be successfully adopted in a rapid laser-scanning microscope,
allowing convenient vibrational imaging of tissue specimens. In our proposal we develop, test, and
improve the new IR-NLO technology. The validation of the technology is achieved through extensive
biomedical imaging studies and comparison with the state of the art IR microscopy available today.
The proposed program tackles a major challenge in IR spectroscopic microscopy, namely the
improvement of imaging resolution. This new capability is significant, as the higher resolution enables
the identification of sub-micrometer intra- and extra-cellular structures in the tissue, which hitherto
have remained invisible in IR-imaging. The high-resolution imaging property thus dramatically
improves the diagnostic capabilities of the technique. By setting a new resolution standard for
fingerprint vibrational imaging, the IR-NLO technology is likely to have a significant impact in tissue
imaging and can enable its use in both research and clinical domains for pathology.

## Key facts

- **NIH application ID:** 9903403
- **Project number:** 5R01GM132506-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Eric Olaf Potma
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $135,129
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9903403

## Citation

> US National Institutes of Health, RePORTER application 9903403, High-resolution spectroscopic imaging with infrared nonlinear optical (IR-NLO) microscopy (5R01GM132506-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9903403. Licensed CC0.

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