Organ-on-chip technology

Image Citation: [1]

Written by: Annabel Ovonlen ‘29

Edited by: Gloria Yao ‘28

For the longest time, scientists have made a habit of investigating diseases and biological functions using cell lines or animal models like mice to provide an organismal perspective before initiating any human trials. In recent years, advances in stem cell biology birthed organoids: stem-cell derived mini 3D tissue cultures that resemble an organ. Recently, with the help of biomedical engineers, there’s a new kid on the block: organ-on-a-chip. 

What is it?

Organ-on–a-chip technology (OOC) refers to microfluidic platforms with multiple channels and chambers containing human cells. They are used to mimic the cellular environment within human organs, model diseases and test drugs. 

Human cells reside in the microfluidic channels and fluids flow through them, allowing for the delivery of nutrients, removal of waste, and the creation of a chemical gradient [2]. OOCs typically contain two channels which are separated by a semipermeable membrane to mimic the physical barriers in real organs and allow for the exchange of substances [3]. Depending on the specialised functions of the organ that is being modelled, extra features may be added. For example, a vacuum channel may be added to simulate inhalation and exhalation of the lungs.  

The concept of an organ-on-a-chip was introduced in 2010 by Dongeun Huh and a team of researchers who created a lung-on-chip [4]. Since then, this technology has become increasingly popular and has been used to model a variety of organs.

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What makes OOCs a good tool in comparison to other models?

OOCs present several advantages over current preclinical models when it comes to resembling human physiological environments. Whilst animal models are useful for investigating how a disease or drug affects a whole organism, unlike OOCs, they don’t contain living human cells. Therefore, there is no guarantee that the results you obtain will translate into humans. OOC technology helps us to avoid this and could help us move away from the ethical issues related to animal experiments.

In comparison to 2D cell cultures which only contain a monolayer of one cell type, OOCs can simulate cell to cell interactions because they can accommodate different cell types in different chambers. Don’t organoids contain different types of cells too? Yes, they do. However, organoids are highly variable because they self-assemble, most lack a vascular system and their functions can’t be sufficiently monitored [6]. By using an OOC, scientists are able to mimic the biomechanics of an organ such as blood flow, control the cellular microenvironment through precise bioengineering, and monitor everything through real-time imaging and integrated sensors [7]. Therefore, they act as a great way to model the complex internal mechanisms of various organ systems. 

Applications:

Due to these clear advantages, many different OOCs have been developed. Including skin, heart, bladder and even hair [4]. This has caught the attention of scientists in the field of reproductive health, and they are now working with OOCs too. 

There is a particular focus on ovarian cancer as it continues to be a leading cause of cancer mortality in women [8]. Ovarian cancer often evades timely evasion due to the lack of a single biomarker and specific symptoms which leads to late diagnosis and poorer outcomes. To bridge this gap, some researchers are using OOC technology to detect biomarkers for ovarian cancer [8,9]. Aside from this, OOC technology has also been used to create ovarian-cancer-on-a-chip technology to investigate how exactly platelet extravasation (leakage) into the tumour environment enables metastasis [8]. 

The research team designed their own ovarian tumour microenvironment chip (OTME-Chip) by building upon a previous ovarian-cancer-on-a-chip that they had made. The OTME-chip has two chambers. To resemble a vascular lumen, the lower chamber contains human ovarian microvascular endothelial cells. The upper chamber acts as the tumour by containing epithelial ovarian cancer cells. Adjacent to the tumour cell chamber, they included ECM chambers separated by polydimethylsiloxane micropillars on the sides. This enabled them to study the cancer’s progression and analyse cancer cell proliferation and invasiveness in response to platelet extravasation. 

Using their OTME-Chip, they found that platelets interact with these tumour cells by binding to them using a receptor called GPVI [10]. This binding induces platelet adhesion and hyperactivity and in turn increases tumour cell proliferation, chemoresistance and metastasis because the platelets form a physical shield around tumor cells which protects them from immune cells [11]. This is exacerbated by the tumor-promoting growth factors and cytokines that extravasated platelets are known to release [10].

Future Outlook: 

As with all technology, OOC technology isn’t perfect and there are still improvements to be made. To further improve on their ability to replicate the complex interactions within an organ, further components need to be added. For example, the inclusion of hormones and immune cells helps take endocrine and immune interactions into account [8,12]. 

Some scientists are proposing that rather than being forced to choose between organoids and OOCs, we can combine the two approaches using synergistic engineering. This combination would have several advantages such as the ability to control the biochemical and biophysical environment of the organoid, and reducing the variability in size, structural organization, functional capacity, and gene expression that is typically associated with organoid development [13].

Overall, organ-on-a-chip technology is a great tool that researchers can add to their arsenal even if its ability to replicate cellular environments can still be improved upon. No one tool can solve anything. OOCs can be used in combination with other models to enhance our understanding of the human body. 

References:

1. Folch A. The Organ-on-a-Chip Revolution Is Here [Internet]. The MIT Press Reader. 2022 [cited 2025 Nov 18]. Available from: https://thereader.mitpress.mit.edu/the-organ-on-a-chip-revolution-is-here/

2. Young RE, Huh DD. Organ-on-a-chip technology for the study of the female reproductive system. Advanced Drug Delivery Reviews [Internet]. 2021 Jun 1 [cited 2025 Nov 5];173:461–78. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0169409X21000843

3. Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, Ingber DE. Reconstituting organ-level lung functions on a chip. Science (New York, NY) [Internet]. 2010 [cited 2025 Nov 2];328(5986):1662–8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/20576885

4. Negar Farhang Doost, Srivastava SK. A Comprehensive Review of Organ-on-a-Chip Technology and Its Applications. Biosensors. 2024 May 1;14(5):225–5.

5. Nayak S, Arya Sondkar, Gayatri Vinchurkar, Shreya Shirsath, Shruti Shintre, Bhaskar Vaidhun. Organs-on-chips Provide Insights into Molecular Mechanisms of Disease and Facilitate the Design of Newer Treatment Strategies: A Concise Review. Journal of Exploratory Research in Pharmacology [Internet]. 2024 Mar 18 [cited 2025 Nov 18];9(2):116–23. Available from: https://www.xiahepublishing.com/2572-5505/JERP-2023-00006S

6. Fan X, Hou K, Liu G, Shi R, Wang W, Liang G. Strategies to overcome the limitations of current organoid technology - engineered organoids. Journal of Tissue Engineering [Internet]. 2025 Apr 1 [cited 2025 Nov 18];16. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC12033597/

7. Srivastava SK, Foo GW, Aggarwal N, Chang MW. Organ-on-chip technology: Opportunities and challenges. Biotechnology Notes [Internet]. 2024 Jan 1 [cited 2025 Nov 18];5:8–12. Available from: https://www.sciencedirect.com/science/article/pii/S2665906924000023#:~:text=Achieving%20physiologically%20relevant%20conditions%20within

8. Lim SY, Aboelnasr LS, El-Bahrawy M. Tumour-on-Chip Models for the Study of Ovarian Cancer: Current Challenges and Future Prospects. Cancers. 2025 Oct 6;17(19):3239.

9. Wu Y, Wang C, Wang P, Wang C, Zhang Y, Han L. A high-performance microfluidic detection platform to conduct a novel multiple-biomarker panel for ovarian cancer screening. RSC Advances. 2021;11(14):8124–33.

10. Saha B, Mathur T, Tronolone JJ, Chokshi M, Lokhande GK, Selahi A, et al. Human tumor microenvironment chip evaluates the consequences of platelet extravasation and combinatorial antitumor-antiplatelet therapy in ovarian cancer. Science Advances [Internet]. 2021 Jul 1 [cited 2025 Nov 2];7(30):eabg5283. Available from: https://pubmed.ncbi.nlm.nih.gov/34290095/

11. Tesfamariam B, Wood SC. Targeting glycoprotein VI to disrupt platelet-mediated tumor cell extravasation. Pharmacological Research. 2022 Aug;182:106301.

12. Yan J, Wu T, Zhang J, Gao Y, Wu J, Wang S. Revolutionizing the female reproductive system research using microfluidic chip platform. Journal of Nanobiotechnology [Internet]. 2023 Dec 19 [cited 2025 Nov 2];21(1). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10729361/

13. Park SE, Georgescu A, Huh D. Organoids-on-a-chip. Science [Internet]. 2019 Jun 6 [cited 2025 Nov 5];364(6444):960–5. Available from: https://science.sciencemag.org/content/364/6444/960.full