Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

Communications Biology
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. communications biology
  3. articles
  4. article
A compatible gravity-driven organoid perfusion (GDOP) platform for drug screening with sensitivity and toxicity process evaluation
Download PDF
Download PDF
  • Article
  • Open access
  • Published: 02 April 2026

A compatible gravity-driven organoid perfusion (GDOP) platform for drug screening with sensitivity and toxicity process evaluation

  • Shun Wang1,
  • Xiaoliang Zhang1,
  • Houshi Ma1,
  • Linlin Lu2,
  • Huabin Jiang3,
  • Yuqiao Bai  ORCID: orcid.org/0000-0001-6835-45164,
  • Xiaoran Chang1,
  • Jinxian Wang  ORCID: orcid.org/0000-0003-3566-69051,4,
  • Tianhang Yang1,5 &
  • …
  • Gangyin Luo1,4 

Communications Biology , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Breast cancer
  • Drug screening
  • Lab-on-a-chip
  • Tissue engineering

Abstract

High-throughput experiments, unidirectional fluid replacement, real-time process monitoring, and simultaneous drug sensitivity and toxicity tests are hard to achieve on most existing tumor organoid chips. Here, we developed a gravity-driven organoid perfusion (GDOP) platform facilitating scalable throughput and supporting drug sensitivity and toxicity assessment on organoids. The unidirectional perfusion capability and optimized operational parameters of the GDOP chip were validated through fluid dynamics simulations. Using this platform, we successfully established uniform on-chip triple-negative breast cancer (TNBC) organoids, with endpoint detection results aligning closely with clinical diagnosis. Throughout the drug treatment process, we monitored and then analyzed the morphological and grayscale changes of the organoids. The sensitivity and toxicity tests revealed the optimal concentration range for the 3 chemotherapeutic drugs. In addition, on-chip brain organoids were established, which lays a feasible foundation for future drug toxicity tests of complex organoids. The GDOP platform, combined with its integrated evaluation method, provides a powerful and reliable approach for advancing organoid-based researches.

Data availability

All the data in this study are available upon reasonable request from the corresponding author. Source data for 840 sample datasets of organoid dimension and grayscale obtained by image recognition are available in Supplementary Data 1. Source data underlying graphs can be obtained from Supplementary Data 2.

Code availability

The code and training results of the developed model have been deposited to GitHub repository (https://github.com/yesterdayzxl/organoidRecognizatrion).

References

  1. Filho, A. M. et al. The GLOBOCAN 2022 cancer estimates: data sources, methods, and a snapshot of the cancer burden worldwide. Int. J. Cancer 156, 1336–1346 (2025).

    Google Scholar 

  2. Sontheimer-Phelps, A., Hassell, B. A. & Ingber, D. E. Modelling cancer in microfluidic human organs-on-chips. Nat. Rev. Cancer 19, 65–81 (2019).

    Google Scholar 

  3. Xu, H. Z. et al. Tumor-microenvironment-on-a-chip: the construction and application. Cell Commun. Signal. 22 https://doi.org/10.1186/s12964-024-01884-4 (2024).

  4. Zhao, Z. X. et al. Organoids. Nat. Rev. Methods Primers 2 https://doi.org/10.1038/s43586-022-00174-y (2022).

  5. Driehuis, E. et al. Pancreatic cancer organoids recapitulate disease and allow personalized drug screening. Proc. Natl. Acad. Sci. USA 116, 26580–26590 (2019).

    Google Scholar 

  6. Drost, J. & Clevers, H. Organoids in cancer research. Nat. Rev. Cancer 18, 407–418 (2018).

    Google Scholar 

  7. Hwangbo, H., Chae, S., Kim, W., Jo, S. & Kim, G. H. Tumor-on-a-chip models combined with mini-tissues or organoids for engineering tumor tissues. Theranostics 14, 33–55 (2024).

    Google Scholar 

  8. Li, W. X. et al. 3D biomimetic models to reconstitute tumor microenvironment in vitro: spheroids, organoids, and tumor-on-a-chip. Adv. Healthc. Mater. 12 https://doi.org/10.1002/adhm.202202609 (2023).

  9. Limjanthong, N. et al. Gravity-driven microfluidic device placed on a slow-tilting table enables constant unidirectional perfusion culture of human induced pluripotent stem cells. J. Biosci. Bioeng. 135, 151–159 (2023).

    Google Scholar 

  10. Wang, Y. I. & Shuler, M. L. UniChip enables long-term recirculating unidirectional perfusion with gravity-driven flow for microphysiological systems. Lab. Chip 18, 2563–2574 (2018).

    Google Scholar 

  11. Lee, D. W., Choi, N. & Sung, J. H. A microfluidic chip with gravity-induced unidirectional flow for perfusion cell culture. Biotechnol. Prog. 35 https://doi.org/10.1002/btpr.2701 (2019).

  12. Park, D. et al. High-throughput microfluidic 3D cytotoxicity assay for cancer immunotherapy (CACI-IMPACT Platform). Front. Immunol. 10 https://doi.org/10.3389/fimmu.2019.01133 (2019).

  13. Yoshimitsu, R. et al. Microfluidic perfusion culture of human induced pluripotent stem cells under fully defined culture conditions. Biotechnol. Bioeng. 111, 937–947 (2014).

    Google Scholar 

  14. Lim, W. & Park, S. A microfluidic spheroid culture device with a concentration gradient generator for high-throughput screening of drug efficacy. Molecules 23 https://doi.org/10.3390/molecules23123355 (2018).

  15. Choi, D. et al. Microfluidic organoid cultures derived from pancreatic cancer biopsies for personalized testing of chemotherapy and immunotherapy. Adv. Sci. 11 https://doi.org/10.1002/advs.202303088 (2024).

  16. Dadgar, N. et al. A microfluidic platform for cultivating ovarian cancer spheroids and testing their responses to chemotherapies. Microsyst. Nanoeng. 6 https://doi.org/10.1038/s41378-020-00201-6 (2020).

  17. Sugiura, S., Edahiro, J., Kikuchi, K., Sumaru, K. & Kanamori, T. Pressure-driven perfusion culture microchamber array for a parallel drug cytotoxicity assay. Biotechnol. Bioeng. 100, 1156–1165 (2008).

    Google Scholar 

  18. Prince, E. et al. Microfluidic arrays of breast tumor spheroids for drug screening and personalized cancer therapies. Adv. Healthc. Mater. 11 https://doi.org/10.1002/adhm.202101085 (2022).

  19. Li, C. J. et al. Pathogenesis and potential therapeutic targets for triple-negative breast cancer. Cancers 13 https://doi.org/10.3390/cancers13122978 (2021).

  20. Sachs, N. et al. A living biobank of breast cancer organoids captures disease heterogeneity. Cell 172, 373 (2018).

    Google Scholar 

  21. Manouchehri, J. M. et al. The role of heparan sulfate in enhancing the chemotherapeutic response in triple-negative breast cancer. Breast Cancer Res. 26 https://doi.org/10.1186/s13058-024-01906-6 (2024).

  22. Abdulla, A. et al. A multichannel microfluidic device for revealing the neurotoxic effects of Bisphenol S on cerebral organoids under low-dose constant exposure. Biosens. Bioelectron. 267, 116754 (2025).

    Google Scholar 

  23. Hofer, M. & Lutolf, M. P. Engineering organoids. Nat. Rev. Mater. 6, 402–420 (2021).

    Google Scholar 

  24. Wasson, E. M., Dubbin, K. & Moya, M. L. Go with the flow: modeling unique biological flows in engineered in vitro platforms. Lab. Chip 21, 2095–2120 (2021).

    Google Scholar 

  25. Yang, T. H. et al. An all-in-one microfluidic cryopreservation system and protocols with gradually increasing CPA concentration. Lab. Chip 25, 565–576 (2025).

    Google Scholar 

  26. Grabinger, T. et al. Ex vivo culture of intestinal crypt organoids as a model system for assessing cell death induction in intestinal epithelial cells and enteropathy. Cell Death Dis. 5, e1228–e1228 (2014).

    Google Scholar 

  27. Klemke, L., Blume, J. P., De Oliveira, T. & Schulz-Heddergott, R. Preparation and cultivation of colonic and small intestinal murine organoids including analysis of gene expression and organoid viability. Bio Protoc. 12, e4298 (2022).

    Google Scholar 

  28. Ferreira, N. et al. OrganoIDNet: a deep learning tool for identification of therapeutic effects in PDAC organoid-PBMC co-cultures from time-resolved imaging data. Cell. Oncol. 48, 101–122 (2025).

    Google Scholar 

  29. Liu, W. M. & Zhang, R. W. Upregulation of p21WAF1/CIP1 in human breast cancer cell lines MCF-7 and MDA-MB-468 undergoing apoptosis induced by natural product anticancer drugs 10-hydroxycamptothecin and camptothecin through p53-dependent and independent pathways. Int. J. Oncol. 12, 793–804 (1998).

    Google Scholar 

  30. Si, P. L. et al. Identification of (S)-10-Hydroxycamptothecin as a potent BRD4 inhibitor for treating triple-negative breast cancer. J. Mol. Struct. 1265 https://doi.org/10.1016/j.molstruc.2022.133366 (2022).

  31. Guo, H. et al. Chitosan-based nanogel enhances chemotherapeutic efficacy of 10-hydroxycamptothecin against human breast cancer cells. Int. J. Polymer Sci. 2019 https://doi.org/10.1155/2019/1914976 (2019).

  32. Zhang, K. F. et al. Mitochondrial-targeted triphenylphosphonium-hydroxycamptothecin conjugate and its nano-formulations for breast cancer therapy: in vitro and in vivo investigation. Pharmaceutics 15 https://doi.org/10.3390/pharmaceutics15020388 (2023).

  33. Li, M. H. et al. Advanced human developmental toxicity and teratogenicity assessment using human organoid models. Ecotoxicol. Environ. Saf. 235 (2022). https://doi.org/10.1016/j.ecoenv.2022.113429

  34. Zhu, Y. J. et al. In situ generation of human brain organoids on a micropillar array. Lab. Chip 17, 2941–2950 (2017).

    Google Scholar 

  35. Namm, A., Arend, A. & Aunapuu, M. Expression of Pax2 protein during the formation of the central nervous system in human embryos. Folia Morphol. 73, 272–278 (2014).

    Google Scholar 

  36. Wang, Y. Q., Wang, L., Zhu, Y. J. & Qin, J. H. Human brain organoid-on-a-chip to model prenatal nicotine exposure. Lab. Chip 18, 851–860 (2018).

    Google Scholar 

  37. Mitchell, M. J. & King, M. R. Computational and experimental models of cancer cell response to fluid shear stress. Front. Oncol. 3, 44–44 (2013).

    Google Scholar 

  38. Ma, H. et al. Drug screening reveals the mechanism of toyocamycin-induced apoptosis in triple-negative breast cancer organoids. Toxicol. Appl. Pharmacol. 506 https://doi.org/10.1016/j.taap.2025.117659 (2026).

  39. Yin, J. & VanDongen, A. M. Enhanced neuronal activity and asynchronous calcium transients revealed in a 3D organoid model of Alzheimer’s disease. ACS Biomater. Sci. Eng. 7, 254–264 (2021).

    Google Scholar 

  40. Parmentier, T., LaMarre, J. & Lalonde, J. Evaluation of neurotoxicity with human pluripotent stem cell-derived cerebral organoids. Curr. Protocols 3 https://doi.org/10.1002/cpz1.744 (2023).

Download references

Acknowledgements

The authors thank the patients for their participation in this study.This work was supported by Natural Science Foundation of Shandong Province, China, ZR2023QE236; the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDC0250301, XDB1150101); 2023 National Health Commission Key Laboratory Special Project (Grant No. 23GSSYA19).

Author information

Authors and Affiliations

  1. Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China

    Shun Wang, Xiaoliang Zhang, Houshi Ma, Xiaoran Chang, Jinxian Wang, Tianhang Yang & Gangyin Luo

  2. The First Affiliated Hospital of Soochow University, Suzhou, China

    Linlin Lu

  3. College of Life Sciences, Shandong Normal University, Jinan, China

    Huabin Jiang

  4. School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China

    Yuqiao Bai, Jinxian Wang & Gangyin Luo

  5. Jinan Guoke Medical Technology Development Co. Ltd, Jinan, China

    Tianhang Yang

Authors
  1. Shun Wang
    View author publications

    Search author on:PubMed Google Scholar

  2. Xiaoliang Zhang
    View author publications

    Search author on:PubMed Google Scholar

  3. Houshi Ma
    View author publications

    Search author on:PubMed Google Scholar

  4. Linlin Lu
    View author publications

    Search author on:PubMed Google Scholar

  5. Huabin Jiang
    View author publications

    Search author on:PubMed Google Scholar

  6. Yuqiao Bai
    View author publications

    Search author on:PubMed Google Scholar

  7. Xiaoran Chang
    View author publications

    Search author on:PubMed Google Scholar

  8. Jinxian Wang
    View author publications

    Search author on:PubMed Google Scholar

  9. Tianhang Yang
    View author publications

    Search author on:PubMed Google Scholar

  10. Gangyin Luo
    View author publications

    Search author on:PubMed Google Scholar

Contributions

S.W. and J.W.—Conceptualization; S.W., H.M., and J.W.—Methodology; S.W., J.W.—Investigation; S.W., H.J., X.C., T.Y., and Y.B.—Validation; S.W. and H.J.—Visualization; S.W., T.Y., and H.M.—Formal analysis; S.W. and T.Y.—Data curation; S.W. and X.Z.—Software; T.Y., J.W., and G.L.—Funding acquisition; J.W. and G.L.—Resources; L.L., J.W., and G.L.—Project administration; J.W., T.Y., and G.L.—Supervision; S.W., H.M., and X.Z.—Writing—original draft; X.C., T.Y., J.W., and G.L.—Writing—review and editing; All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Jinxian Wang, Tianhang Yang or Gangyin Luo.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Communications Biology thanks the anonymous reviewers for their contribution to the peer review of this work. Primary Handling Editors: Dr Shirley Tang and Dr Ophelia Bu.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information (download PDF )

Description of Additional Supplementary Files (download PDF )

Supplementary Data 1 (download XLSX )

Supplementary Data 2 (download XLSX )

Supplementary Video S1 (download MP4 )

Supplementary Video S2 (download MP4 )

Reporting Summary (download PDF )

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, S., Zhang, X., Ma, H. et al. A compatible gravity-driven organoid perfusion (GDOP) platform for drug screening with sensitivity and toxicity process evaluation. Commun Biol (2026). https://doi.org/10.1038/s42003-026-09973-5

Download citation

  • Received: 30 April 2025

  • Accepted: 20 March 2026

  • Published: 02 April 2026

  • DOI: https://doi.org/10.1038/s42003-026-09973-5

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Download PDF

Advertisement

Explore content

  • Research articles
  • Reviews & Analysis
  • News & Comment
  • Collections
  • Follow us on X
  • Sign up for alerts
  • RSS feed

About the journal

  • Journal Information
  • Open Access Fees and Funding
  • Journal Metrics
  • Editors
  • Editorial Board
  • Calls for Papers
  • Referees
  • Contact
  • Editorial policies
  • Aims & Scope

Publish with us

  • For authors
  • Language editing services
  • Open access funding
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

Communications Biology (Commun Biol)

ISSN 2399-3642 (online)

nature.com footer links

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2026 Springer Nature Limited

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer