# Light engineering module for fast high-resolution whole-cell imaging

> **NIH NIH R43** · DOUBLE HELIX OPTICS INC. · 2020 · $218,223

## Abstract

Summary
This Small Business Innovation Research (SBIR) Phase I project is focused on the design, development, and
testing of a ground-breaking multidimensional multifunctional quantitative optical microscopy module suitable for
live whole cell studies. The module will utilize Light Engineering to achieve fast high-sensitivity, low-noise, high-
resolution measurements down to the single-molecule level while providing wide volumetric field of view.
In spite of the ongoing revolution in optical microscopy, the availability of state-of-the-art commercial solutions
has been slow to market, lacking in flexibility, ease of access and affordability.
The proposed 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 photo-damage and photo-toxicity. The engineering of the 3D point
spread function enables multiplex functionality including an extended depth of field, high-sensitivity 3D
localization of single-molecules or cellular heterogeneities, multi-color, and 3D imaging. The integrated system
will enable reconstruction with superb sectioning capability. As a result, the target performance metrics,
supported by recent research demonstrations in academic labs, outperform the state of the art in terms of
spatial/temporal resolution, signal-to-noise ratio, field of view, and ease of use.
This SBIR project is targeted towards commercialization of a cost-effective solution that can be easily integrated
with existing scientific microscopes. The commercial module, to be developed from the Phase I 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 further assist in stem cell and brain research.
Double Helix Optics is a startup company with a proven record and 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 successfull...

## Key facts

- **NIH application ID:** 9910043
- **Project number:** 1R43EB028726-01A1
- **Recipient organization:** DOUBLE HELIX OPTICS INC.
- **Principal Investigator:** WARREN COLOMB
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $218,223
- **Award type:** 1
- **Project period:** 2020-06-01 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9910043

## Citation

> US National Institutes of Health, RePORTER application 9910043, Light engineering module for fast high-resolution whole-cell imaging (1R43EB028726-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9910043. Licensed CC0.

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