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PreprintCC BY-NC-NDbioRxiv

Microdomes: Micro-engineered Microdome arrays enable standardised and shear-free 3D biology with full-spectrum optical imaging compatibility

7 more authors
  1. 1Katharina Gaus Light Microscopy Facility (KGLMF), Mark Wainwright Analytical Centre, Lowy Cancer Research Centre, The University of New South Wales, Sydney, Aus

Abstract

Three-dimensional cellular models such as organoids and spheroids hold major promise for developmental biology, disease modelling and precision medicine, yet their large-scale production and analysis remain constrained by handling-induced shear stress, sample fragility, positional instability and limited compatibility with advanced imaging workflows. Here, we introduce Microdomes, dense arrays of open-top, dome-shaped microcavities. Each cavity holds a single specimen in its own miniature aquarium, accessed through a narrow apical opening that admits cells, medium, matrix and staining reagents while shielding it from the shear generated during routine pipetting. Each Microdomes chip accommodates more than 100 spheroids or organoids, supporting diverse cell types, co-culture formats and both matrix-free and matrix-embedded culture. All specimens are retained through prolonged culture, repeated medium exchange, fixation and immunostaining. Because every specimen occupies a fixed, addressable position against a thin transparent film, the same spheroid can be relocated and re-imaged over weeks of culture and across microscopes, from array-wide overviews to subcellular details, without transfer, embedding or other perturbation. Microdomes also support AI-based automated segmentation, from whole-spheroid outlines to individual nuclei in 3D, using common image analysis software. Microdomes thereby turn each array into a self-contained quality control unit, providing specimen-level traceability that organoid production pipelines currently lack.

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BibTeX
@misc{cheam2026microdomes,
  title = {{Microdomes: Micro-engineered Microdome arrays enable standardised and shear-free 3D biology with full-spectrum optical imaging compatibility}},
  author = {M. S. Cheam and S. Binte Mohamad Raffi and H. T. Ong and S. E. Ghayad and M. Le Grand and E. Pasquier and P. Dunbabin and K. Poole and J. F. L. Chin and L. Jun and E. Karatas and N. S. J. Lim and J. T. C. Lim and M. Ganguly and A. Ferguson and V. Angeli and Y. Toyama and G. Grenci and A. Beghin},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.10.750786},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.10.750786v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - Microdomes: Micro-engineered Microdome arrays enable standardised and shear-free 3D biology with full-spectrum optical imaging compatibility
AU  - M. S. Cheam
AU  - S. Binte Mohamad Raffi
AU  - H. T. Ong
AU  - S. E. Ghayad
AU  - M. Le Grand
AU  - E. Pasquier
AU  - P. Dunbabin
AU  - K. Poole
AU  - J. F. L. Chin
AU  - L. Jun
AU  - E. Karatas
AU  - N. S. J. Lim
AU  - J. T. C. Lim
AU  - M. Ganguly
AU  - A. Ferguson
AU  - V. Angeli
AU  - Y. Toyama
AU  - G. Grenci
AU  - A. Beghin
PY  - 2026
DA  - 2026/09/10
PB  - bioRxiv
DO  - 10.64898/2026.09.10.750786
UR  - https://www.biorxiv.org/content/10.64898/2026.09.10.750786v1
AB  - Three-dimensional cellular models such as organoids and spheroids hold major promise for developmental biology, disease modelling and precision medicine, yet their large-scale production and analysis remain constrained by handling-induced shear stress, sample fragility, positional instability and limited compatibility with advanced imaging workflows. Here, we introduce Microdomes, dense arrays of open-top, dome-shaped microcavities. Each cavity holds a single specimen in its own miniature aquarium, accessed through a narrow apical opening that admits cells, medium, matrix and staining reagents while shielding it from the shear generated during routine pipetting. Each Microdomes chip accommodates more than 100 spheroids or organoids, supporting diverse cell types, co-culture formats and both matrix-free and matrix-embedded culture. All specimens are retained through prolonged culture, repeated medium exchange, fixation and immunostaining. Because every specimen occupies a fixed, addressable position against a thin transparent film, the same spheroid can be relocated and re-imaged over weeks of culture and across microscopes, from array-wide overviews to subcellular details, without transfer, embedding or other perturbation. Microdomes also support AI-based automated segmentation, from whole-spheroid outlines to individual nuclei in 3D, using common image analysis software. Microdomes thereby turn each array into a self-contained quality control unit, providing specimen-level traceability that organoid production pipelines currently lack.
ER  -