# Light Engineering Module for Fast High-Resolution Whole-Cell Imaging

> **NIH NIH R44** · DOUBLE HELIX OPTICS INC. · 2022 · $722,136

## Abstract

Summary
This SBIR Phase II project is focused on the design refinement, development, and testing of a ground-breaking
multidimensional multifunctional quantitative optical microscopy modular system suitable for live whole cell
studies. The proposed Light Engineering modular system addresses the critical need for flexible imaging
techniques to image live whole cells with low photodamage and phototoxicity while providing high spatial and
temporal resolution as well as a large volumetric field of view.
Despite extraordinary advances in optical microscopy, the availability of state-of-the-art commercial solutions
has been slow to market, lacking in flexibility and ease of access. The modular instrument is based on an
integrated design of the illumination, 3D optical response, data collection, and reconstruction algorithms for
fluorescence imaging. Specifically, engineered 3D light excitation limits the background noise while reducing
photodamage and phototoxicity. The engineered 3D point spread functions enable multiplex functionality
including an extended depth of field imaging, high-sensitivity 3D localization of single-molecules or cellular
heterogeneities, multi-color, and 3D imaging. As a result, the target performance outperforms the state of the art
in terms of spatial/temporal resolution, signal-to-noise ratio, field of view, single-molecule localization precision,
and ease of use.
This project is targeted towards commercialization of a cost-effective modular solution that can be easily
integrated with existing scientific microscopes. The commercial-ready prototype, will include a small footprint
architecture, a set of novel optical phase masks for point spread function engineering and excitation shaping, a
robust optomechanical design, and real-time experiment control software. Tests of the instrument in significant
biomedical problems at partners’ labs will validate end-user acceptance and provide valuable feedback towards
commercialization.
The implications in biomedical imaging are far-reaching. For instance, the instrument would benefit the study of
oncogenesis, owing to its degree of molecular sensitivity for detecting the spatial localization of receptors and
other signaling molecules within the tumor/extracellular matrix. It would also empower the study of degenerative
diseases where the instrument can help reveal their molecular origin and develop novel therapeutic strategies.
The new imaging capabilities could also advance stem cell, cancer and brain research.
Double Helix Optics is a startup company with exclusive licensing rights to the Light Engineering technology from
the University of Colorado, as well as the novel Tetrapod and Multicolor PSF localization developments from
Stanford University. The company, headquartered in the BioFrontiers Institute in Boulder, is optimally positioned
to successfully bring this product to market.

## Key facts

- **NIH application ID:** 10478167
- **Project number:** 5R44EB028726-03
- **Recipient organization:** DOUBLE HELIX OPTICS INC.
- **Principal Investigator:** WARREN COLOMB
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $722,136
- **Award type:** 5
- **Project period:** 2020-06-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10478167

## Citation

> US National Institutes of Health, RePORTER application 10478167, Light Engineering Module for Fast High-Resolution Whole-Cell Imaging (5R44EB028726-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10478167. Licensed CC0.

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