# Multiscale microscope for 3D cancer imaging in model organisms and organoids

> **NIH NIH R33** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $300,887

## Abstract

Fluorescence microscopy is an indispensable tool for the quantitative analysis of the
molecular pathways involved in disease. Importantly, heterotypic cell-cell and cell-matrix
interactions within the 3D tumor microenvironment critically influences signaling pathways and
hence the tumorigenicity of cancer cells. Therefore, it is important to study cancer cells in
physiologically relevant conditions, which can be realized by using model organisms or
organotypic organoid cultures. However, technological limitations prevent the observation of
cancer cell dissemination and survival throughout an entire organism with sufficient
spatiotemporal resolution to evaluate the molecular pathways and oncogenic states of individual
cancer cells. Here, we propose to break through this barrier by developing a new optical
microscope that is capable of longitudinally imaging an entire organism, but can also provide
local high-resolution imaging. Furthermore, it can also perform 3D photo-manipulation, which
allows temporally and spatially confined perturbation of intracellular signaling, modification of
the microenvironment, and tagging cells of interest. The most important properties of the new
microscope are i) multi-scale imaging at cellular and subcellular level, ii) minimal light exposure
to allow long observation spans while limiting photo-toxicity, iii) increased optical penetration
depth via adaptive optics, iv) isotropic spatial resolution in the high-resolution mode and v) 3D
photo-manipulation using two-photon absorption. Optical modules will be developed that enable
tunable light-sheet control, wavefront correction for adaptive optics, 3D scanning for photo-
manipulation and variable magnification of the detection path. Thus, for the first time, this
instrument will allow us to image cancer cell dissemination on an organism scale over extended
time periods and also monitor and manipulate cell signaling states and morphodynamics with
sub-micron, isotropic resolution in metastatic niches.

## Key facts

- **NIH application ID:** 10102640
- **Project number:** 5R33CA235254-03
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Reto Paul Fiolka
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $300,887
- **Award type:** 5
- **Project period:** 2019-02-13 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10102640

## Citation

> US National Institutes of Health, RePORTER application 10102640, Multiscale microscope for 3D cancer imaging in model organisms and organoids (5R33CA235254-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10102640. Licensed CC0.

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