A workflow integrating organ-on-chip culture and correlative 3D light and electron microscopy for microtissue analysis

  • Judith M. Schaart
  • , Dorothee Wasserberg
  • , Marcos A.Eufrásio Cruz
  • , Mariska Kea-te Lindert
  • , Robin H.M. van der Meijden
  • , Rona Roverts
  • , Nataliya Debera
  • , Minh Phu Lu
  • , Jeroen Rouwkema
  • , Wouter H. Nijhuis
  • , Andries D. van der Meer
  • , Pascal Jonkheijm*
  • , Nico Sommerdijk*
  • , Anat Akiva*
  • *Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    Abstract

    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.

    Original languageEnglish
    Article number43666
    Number of pages16
    JournalScientific Reports
    Volume15
    Issue number1
    DOIs
    Publication statusPublished - Dec 2025

    Keywords

    • Bone-on-a-chip
    • Correlative light and electron microscopy
    • Live fluorescence microscopy
    • Organ-on-a-chip
    • Volume electron microscopy

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