# Milling with Ultraviolet Excitation for Whole Organ Cellular-Level Phenotyping

> **NIH NIH R41** · SWIFT FRONT, LLC · 2021 · $251,417

## Abstract

PROJECT SUMMARY
Many diseases, including neurodegenerative disease and cancer, induce complex changes to tissue
microstructure. These include alterations in the microvasculature, cellular distribution, and neural connectivity.
Researchers recognize that highly localized events, such as inflammation, lesions, and activated microglia,
impact the formation of regional pathologies, such as heterogeneous tumors and neurodegenerative disease.
These rare events are challenging to detect using traditional histology, given limitations in the field-of-view of
optical microscopes and the lack of a three-dimensional histological context. The inability to comprehensively
measure large-scale three-dimensional tissue microstructure leaves a critical gap in our understanding
of neurodegenerative disease, limiting our ability to quantify new mechanisms for diagnosis and
treatment.
This proposal addresses this through commercialization of a high-throughput platform enabling multiplex three-
dimensional imaging at rates over 1000X faster than existing microscopy. First, this proposal allows for the
automation and transfer of published and patented imaging technology from the University of Houston to Swift
Front, LLC. This novel imaging method, which we term milling with ultraviolet excitation (MUVE), enables
acquisition of 400 million pixels per second with 3-channel molecular specificity, allowing three-dimensional sub-
micrometer (≈1µm3) resolution imaging of 1cm3 samples in less than one hour. Samples are rapidly imaged
through a combination of fast wide-field fluorescence imaging, deep-ultraviolet excitation, and serial ablation
methods. This proposal will support Swift Front's development of MUVE-compatible tissue labeling and
processing protocols that will readily integrate with existing histology pipelines.
State-of-the-art three-dimensional light-sheet imaging systems are constrained to 100μm thick samples, with the
potential for 3-8mm depth with clearing and low numerical aperture objectives. Although these techniques have
been proposed for samples approaching 1cm3, these methods are incompatible with routine phenotyping
because they are slow, costly, and research lacks accessible computational tools for useful analysis.
MUVE significantly increases acquisition speed by combining recent research in ultraviolet excitation with highly
parallel data collection. This instrumentation also eliminates depth constraints inherent to optical microscopy by
using new en bloc labeling techniques combined with tissue ablation. Our goal is to commercialize a platform
that enables routine imaging, reconstruction, and analysis of large-scale phenotypes describing tissue
microstructure and protein distribution. The availability of a platform for systematic tissue phenotyping and
mapping will fundamentally impact biomedical research and education at the organ scale in the same way that
satellite imagery, global positioning, and search algorithms have changed navigation.

## Key facts

- **NIH application ID:** 10143764
- **Project number:** 1R41GM140586-01
- **Recipient organization:** SWIFT FRONT, LLC
- **Principal Investigator:** Tasha Womack
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $251,417
- **Award type:** 1
- **Project period:** 2021-09-21 → 2023-09-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10143764

## Citation

> US National Institutes of Health, RePORTER application 10143764, Milling with Ultraviolet Excitation for Whole Organ Cellular-Level Phenotyping (1R41GM140586-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10143764. Licensed CC0.

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