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The OrganiX microfluidic system to recreate the complex tumour microenvironment

Nature Reviews Immunology volume 24, page 307 (2024)Cite this article

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Three-dimensional (3D) tumour models, such as organotypic spheroids, patient-derived organoids and tissue explants, preserve critical tumour characteristics for therapeutic screening. However, they often lack key components of the tumour microenvironment (TME), such as extracellular matrix (ECM), immune cells and a perfusable vascular network, that influence tumour progression and therapy responses. To address these limitations, we have developed various human 3D tumour models using an ECM-like hydrogel and increased cellular complexity in microfluidic devices1,2.

Understanding the complex interactions among tumour cells, immune cells, stromal cells and the vascular network is crucial for evaluating how tumours respond to treatment. The OrganiX microfluidic system allows easy and efficient functional testing to optimize drugs and cell-based therapies. For example, the system has been used to show how the vasculature network and spatiotemporal dynamics of the TME influence the effector functions of T cells engineered to express tumour-specific T cell receptors or chimeric antigen receptors4. The versatility of this system provides a distinct advantage over traditional animal models, by enabling researchers to manipulate physical parameters (such as ECM stiffness), adjust biochemical conditions (including cytokines and drugs) and introduce specific immune or stromal cells for easy customization of the experimental design.

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Fig. 1: Microfluidic device for vascularized 3D tumour models.

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Authors and Affiliations

  1. Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore

    Giulia Adriani

  2. Department of Biomedical Engineering, National University of Singapore (NUS), Singapore, Singapore

    Giulia Adriani

  3. Institute of Molecular and Cell Biology, A*STAR, Singapore, Singapore

    Andrea Pavesi

  4. Mechanobiology Institute, NUS, Singapore, Singapore

    Andrea Pavesi

Authors
  1. Giulia Adriani
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  2. Andrea Pavesi
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Correspondence to Giulia Adriani or Andrea Pavesi.

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Competing interests

G.A. and A.P. are co-inventors on a US patent application (US20240018483A1) and an international patent application (WO 2022/197254 A1) describing microfluidic technologies and a method for 3D vascularization. G.A. and A.P. are co-inventors of the OrganiXTM plate, licensed to AIM Biotech. A.P. is a consultant and shareholder of AIM Biotech Pte. Ltd.

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Adriani, G., Pavesi, A. The OrganiX microfluidic system to recreate the complex tumour microenvironment. Nat Rev Immunol 24, 307 (2024). https://doi.org/10.1038/s41577-024-01011-x

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