# Rapid and high-contrast photothermal microscopy with a novel tunable ZGP source

> **NIH NIH R43** · TRESTLE OPTICS LLC · 2023 · $305,647

## Abstract

Abstract.
Natural products offer excellent sources of health-promoting medicines yet challenges in
efficiently and economically sourcing these value-add bio-compounds have prevented their
greater availability and promotion to public health. We address this problem by developing a novel
image-based screening technology that offers highly sensitive, phenotypic bioassays of
metabolite concentrations on live single cells. This allows a greatly improved method for
identification of better natural product producers, as well as quantitative information about the
production per cell and production distribution across the population. This high-resolution, non-
destructive, label-free cell screening and cell sorting system is based on vibrational photothermal
microscopy which uses mid-infrared light to probe molecular vibrational absorptions at resolutions
comparable to visible light microscopes. To demonstrate the utility of the approach we focus on
the production of essential polyunsaturated fatty acids (PUFAs) in lipid droplets sourced from
microalgae (thraustochytrids) – a natural producer of PUFAs. These long-chain fatty acids play a
vital role in the physiological health of cells and tissues throughout the body are commercialized
as a prominent nutraceutical. To develop enriched cell lines, we will engineer and prototype a
multichannel microfluidic chip with an active piezoelectric actuator to selectively save cells
identified through photothermal as being highly productive. Our goal is to provide an attractive
method to non-destructively evaluate metabolite content in engineered microbes including
bacteria and yeast, not just algae, and for a variety of high-value metabolites. To accomplish
these goals, we have established a team of qualified experts including specialists in advanced
microscopy, microfluidics design, and algae cultivation for industrial applications. Ultimately, the
methods developed here will showcase a roadmap toward rare-cell discovery and active cell
sorting based on chemical mapping allowed through the photothermal imaging contrast.

## Key facts

- **NIH application ID:** 10600781
- **Project number:** 1R43GM149004-01
- **Recipient organization:** TRESTLE OPTICS LLC
- **Principal Investigator:** Adam M Hanninen
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $305,647
- **Award type:** 1
- **Project period:** 2023-09-05 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10600781

## Citation

> US National Institutes of Health, RePORTER application 10600781, Rapid and high-contrast photothermal microscopy with a novel tunable ZGP source (1R43GM149004-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10600781. Licensed CC0.

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