A workflow integrating organ-on-chip culture and correlative 3D light and electron microscopy for microtissue analysis
Correlative microscopy approaches offer powerful means to study tissue development across spatial scales, but combining 3D light and electron imaging remains technically challenging. Here, we present a practical workflow that integrates organ-on-a-chip culture with longitudinal fluorescence imaging and volume electron microscopy. By modifying an existing chip platform designed for aligned tissue growth, we demonstrate the feasibility of extended 3D live imaging and subsequent high-pressure freezing of intact microtissues. Fluorescence-guided targeting enables focused ion beam/scanning electron microscopy (FIB/SEM) of selected regions, revealing ultrastructural features such as cellular organization, collagen alignment, and matrix mineralization. While not aimed at new biological discoveries, this study highlights the compatibility and potential of this pipeline for future high-resolution, multiscale studies of tissue morphogenesis and pathology in controlled microenvironments.
Authors
- Dorothee Wasserberg (ORCID: https://orcid.org/0000-0002-1493-2971)
- Rona Roverts (ORCID: https://orcid.org/0000-0002-0967-6694)
- Nico A. J. M. Sommerdijk (ORCID: https://orcid.org/0000-0002-8956-195X)
- Anat Akiva (ORCID: https://orcid.org/0000-0003-0414-889X)
- Robin H.M. van der Meijden (ORCID: https://orcid.org/0000-0002-0611-2578)
- Pascal Jonkheijm (ORCID: https://orcid.org/0000-0001-6271-0049)
- Andries D. van der Meer (ORCID: https://orcid.org/0000-0002-8761-4077)
- Judith M. Schaart (ORCID: https://orcid.org/0009-0009-7237-7214)
- Wouter H. Nijhuis (ORCID: https://orcid.org/0000-0001-6683-7549)
- Mariska Kea‐te Lindert
- Jeroen Rouwkema (ORCID: https://orcid.org/0000-0001-9666-9064)
- Marcos Antônio Eufrásio Cruz (ORCID: https://orcid.org/0000-0003-2199-7439)
- Nataliya Debera
- Minh Phu Lu
Institutions
- Radboud University Nijmegen (NL)
- Radboud University Medical Center (NL)
- Radboud Institute for Molecular Life Sciences (NL)
- Wilhelmina Children's Hospital (NL)
- University of Twente (NL)
Publication Details
- Journal
- Scientific Reports
- Published
- 2025-12-11
- DOI
- https://doi.org/10.1038/s41598-025-27587-5
- Primary Topic
- Advanced Electron Microscopy Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Radboud Universiteit
- University of Twente
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Horizon 2020 Framework Programme
- Topconsortium voor Kennis en Innovatie