# Expansion Optical Coherence Microscopy (ExOCM)

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2022 · $236,250

## Abstract

Project Summary
Inspired by recent advances in expansion microscopy (ExM), we propose to develop a new technology called
expansion optical coherence microscopy (ExOCM). Using a standard optical coherence tomography (OCT) or a
high-resolution OCM system, we will obtain super-resolution, molecular-specific images of expanded tissue
samples. Our recent pilot experiment demonstrated that intrinsic scattering signals from expanded samples can
be observed using OCT, demonstrating the feasibility of ExOCM based on intrinsic scattering contrast. To further
enable molecular-specific imaging, contrast agents, such as gold nanoparticles (GNPs), molecular dyes, and
even fluorescence proteins, with different light absorption profiles can be selected for multi-color ExOCM.
Compared to standard ExM, ExOCM can image extra thick samples at high speed. This approach also allows
the co-registration of three-dimensional (3D) molecular profiles with live tissue microstructures obtained from the
same specimen using label-free OCT. Building upon our group’s extensive expertise in developing OCT and
OCM technologies and experience with 3D organoid models, we propose to develop, optimize and validate
ExOCM technology, and demonstrate the unique attributes of ExOCM for biomedical research. Two specific
aims of the proposed program are: Aim 1. To develop and optimize ExOCM technology for multi-color, super-
resolution imaging of expanded organoids. We will optimize an ultrahigh-resolution OCM system to achieve ~1.5
µm isotropic image resolution. Antibody conjugated GNPs will be used to provide selective targeting for specific
proteins. Using our optimized OCM system and a ~4.5X tissue expansion protocol, we expect to obtain a ~300
nm resolution in both the axial and transverse dimensions. Multi-color and multiplexed imaging will be obtained
using spectroscopic OCT analysis to separate signals from GNPs with different absorption and scattering
profiles. Aim 2. To validate ExOCM with two-photon microscopy, and to demonstrate the feasibility of the
combined OCT and ExOCM imaging approach to characterize 3D structural and molecular profiles and growth
dynamics from the same samples. We will use OCT to acquire longitudinal, label-free images of living organoids
over a three-week time-course. At predetermined time points, samples will be expanded for ExOCM and two-
photon imaging, where tissue structural landmarks will be identified from 3D image stacks for registration.
ExOCM imaging data collected during the expansion process will provide first-hand information about 3D
expansion uniformity. Complementary 3D structural and molecular profiles and growth dynamics from the same
organoids will be obtained, demonstrating the unique advantages of the combined OCT and ExOCM imaging
approach. If successful, the integrated OCT and ExOCM imaging platform will prove helpful for applications in
developmental biology, cancer research and regenerative medicine. Furthermore, high-throughput
...

## Key facts

- **NIH application ID:** 10530971
- **Project number:** 1R21EB032684-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Chao Zhou
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $236,250
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10530971

## Citation

> US National Institutes of Health, RePORTER application 10530971, Expansion Optical Coherence Microscopy (ExOCM) (1R21EB032684-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10530971. Licensed CC0.

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