Organ-on-a-chip: Miniature organs with a big impact

Imagine a world where we can study human organs without invasive procedures or animal testing. Thanks to organ-on-a-chip (OOC) technology, this is now a reality. These miniature organs are transforming drug development and biomedical research, offering new insights into human physiology in a controlled environment — read on to learn how.

Organ-on-a-chip models are 3D microfluidic devices that mimic the functions and responses of an entire organ or organ system in vitro.^1,2 Often no larger than a USB drive, these microfluidic devices contain living human cells arranged to simulate the structure and function of human organs.³ By recreating the microenvironment of specific organs, these systems offer a more accurate representation of human physiology than traditional 2D cell cultures.^1,2

Organ-on-a-chip systems integrate various cell types and extracellular matrices arranged in 3D structures to recreate the microenvironment of human organs (Figure 1).⁴ They also incorporate microfluidic channels that mimic blood flow, thereby providing continuous nutrient supply and waste removal. In addition, these systems can integrate mechanical forces to simulate organ function.⁴ Common sources of cells used in organ-on-a-chip systems include endothelial cells, epithelial cells, fibroblasts, human cardiac myocytes, and immune cells.^2,5 These cells are carefully cultured within the microfluidic channels of the chip, allowing the study of their interactions and responses to various stimuli, including potential drug compounds.^2,6 The design of the systems varies depending on the organ being modeled. For instance, lung-on-a-chip systems typically incorporate stretching motions to simulate breathing, while liver-on-a-chip devices focus on replicating the complex metabolic functions of hepatocytes.^7,8

Figure 1: Schematic illustration of organ-on-a-chip systems.

Components, structure, and design of organ-on-a-chip technology. From Cho S et al., 2023.⁴

Organ-on-a-chip technologies have a wide range of applications in drug development and biomedical research.

• Drug discovery: These devices enable rapid screening of drug candidates, potentially reducing the time and cost of bringing new medications to market.⁹
• Disease modeling: Researchers can recreate disease conditions on chips, offering new insights into disease mechanisms and potential treatments.¹⁰ For example, cancer-on-a-chip models have been developed for the study of tumor growth and metastasis.¹¹
• Toxicity testing: Organ-on-a-chip models provide a more accurate platform for assessing the toxicity of new compounds compared to traditional 2D cell cultures.¹² This is particularly valuable for industries like cosmetics and environmental health, where animal testing is increasingly restricted.¹³
• Personalized medicine: By incorporating a patient’s own cells, these systems can help predict individual responses to treatment.¹⁴ This could lead to more tailored therapeutic approaches, reducing the risk of adverse reactions and improving treatment outcomes.
• Immunology research: These systems allow for detailed study of immune responses in a controlled environment.¹⁵ This is particularly valuable for understanding autoimmune diseases, allergies, and the body’s response to pathogens.
• Blood-brain barrier studies: Specialized chips modeling the blood-brain barrier can help us understand how drugs penetrate this crucial protective layer, potentially leading to more effective treatments for neurological disorders.¹⁶

Organ-on-a-chip technology offers several advantages over traditional research methods (Figure 2):

• Physiological relevance, providing a more accurate representation of human physiology than 2D cell cultures or animal models.¹⁷
• Ability to study organ-specific effects of drugs, helping to predict organ toxicity early in the drug development process.¹⁸
• Real-time monitoring of cellular responses, allowing for dynamic studies of drug effects over time.¹⁹
• Opportunity to incorporate multiple cell types into a single chip, enabling the study of complex cell-cell interactions.⁶
• Potential for personalized drug testing using patient-derived cells.¹⁹
• Reduced cost and time in drug development processes by enabling more efficient screening of drug candidates.¹⁹
• A more ethical research platform that doesn‘trely on animal testing, addressing concerns related to the use of animal models.²⁰
• Possibility to model rare diseases or patient-specific conditions that may be difficult to study in animal models.²¹

Figure 2: Advantages and challenges of organs-on-a-chip.

Schematic illustration of the key benefits of OOC over traditional research methods, as well as their limitations.

Despite their several advantages over traditional research models, organ-on-a-chip systems face barriers to their widespread use (Figure 2):

• Absorption issues: Some chip materials can absorb small molecules, potentially affecting experimental results.²²
• Fragility: The delicate nature of these devices can make them challenging to work with, requiring specialized handling and expertise.²³
• Scalability: Scaling up production of these systems for high-throughput screening can be difficult.²⁴
• Standardization: There’s a lack of universally accepted protocols and materials for developing these models, making it challenging to compare results across different labs and experiments.²⁵
• Complexity: Recreating the full complexity of human organs remains a significant challenge. Although these systems are more physiologically relevant than 2D cultures, they can’t fully replicate the complexity of human organs.^24,26
• Long-term viability: Maintaining cells in a functional state on a chip for extended periods can be challenging, limiting the ability to study long-term effects or chronic conditions.⁵

This field is evolving rapidly. Researchers are working on connecting multiple organ chips to create ‘body-on-a-chip’ systems, which could provide insights into complex inter-organ interactions and systemic effects of drugs.²⁷ Standardization efforts are also a key focus, aiming to develop universally accepted protocols and materials. Ensuring consistent and reproducible results across different laboratories and experiments is crucial for the successful translation of findings from organ-on-chipmodels.²⁶ Moreover, efforts are ongoing to develop new materials that minimize the risk of inaccurate findings due to chip materials absorbing small molecules. For example, the use of glass-based devices has been proposed to minimize small molecule absorption by materials used in organ-on-a-chip models.²² In addition, the integration of more sophisticated sensors into organ-on-a-chip devices could allow for even more detailed real-time monitoring of cellular responses.²⁸ As the technology matures and guardrails for standardization are developed, increased adoption in the pharmaceutical and biotechnology industries is expected.²⁹

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