# Imaging Cells and Tissues with Super-Resolution Structured Illumination Microscopy

> **NIH NIH R15** · UNIVERSITY OF COLORADO · 2023 · $99,948

## Abstract

Imaging Cells and Tissues with Super-Resolution Structured Illumination Microscopy - Project
Summary
Fluorescence optical microscopy is one of the most important tools available for the study of
biological systems at the cellular level. Unfortunately, due to diffraction phenomena the
resolution of fluorescence microscopes in the lateral dimension is limited to about 250 nm. As
many biological structures within cells are much smaller than this, increasing resolution is of
prime importance. Although several methods are now available which are able to extend the
resolution of optical microscopes beyond the diffraction limit, imaging cells and tissues with
these methods remains a challenge.
Super-resolution structured illumination microscopy (SIM), which can achieve a resolution of
approximately 100 nm, is a suitable super-resolution method for cells and tissues. However,
adoption of this technique by biologists is hindered by the inflexible equipment and artifact-
prone image analysis algorithms which are currently available. The solution to this problem
demands innovations in both optical design and in data processing methods which are used in
SIM. In particular, imaging deeper into tissues with SIM has not been realized so far.
The goal of this interdisciplinary project is to develop, improve, and utilize super-resolution
microscopy with a focus on imaging both cells and tissues. In Aim 1 we will develop alternative
illumination approaches for SIM using economical components, and we will develop and
implement improved SIM reconstruction algorithms which produce results with higher resolution,
quality, and more reliable results than are available with current methods. These methods will
allow imaging into tissues up to 500 micrometers, about 10-fold better than current technology
allows. In Aim 2, we will develop new algorithms based on machine learning for optical
sectioning microscopy and for denoising of microscopy images. In Aim 3, we will use the newly
developed suite of methods for studies of the molecular basis of allergic responses. We will use
structured illumination microscopy to study the relationship between cell surface receptors and
the morphology of the plasma membrane, and we will develop a reaction-diffusion model to
better understand the biophysics of the cell membrane.

## Key facts

- **NIH application ID:** 10796461
- **Project number:** 3R15GM128166-02S1
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** Guy Hagen
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $99,948
- **Award type:** 3
- **Project period:** 2018-07-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10796461

## Citation

> US National Institutes of Health, RePORTER application 10796461, Imaging Cells and Tissues with Super-Resolution Structured Illumination Microscopy (3R15GM128166-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10796461. Licensed CC0.

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