Researchers have made a lot of progress in creating brain organoid-on-chip platforms that are equipped with advanced sensors. These platforms open up new ways to study neuronal activity and neurotoxicity. These breakthroughs promise to enhance our understanding of neurological disorders and improve the efficacy of drug screening processes. The findings were published in the journal Microchimica Acta.
Brain organoids, often described as “mini-brains”, are three-dimensional models derived from human-induced pluripotent stem cells (iPSCs). These organoids replicate the complex structure and function of the human brain, making them invaluable for studying neurodevelopmental processes and disease pathology. Traditional brain organoid models have faced challenges related to their reproducibility and scalability. But recent advancements have addressed many of these issues, particularly through the integration of microfluidic systems and real-time sensing technologies.
Ozlem Yesil Celiktas, PhD, a professor of bioengineering at Ege University in Turkey, notes the significance of these advancements: “Recent advancements in brain organoids, microfluidic systems, and real-time sensing technologies, as well as their integrated use, provide excellent models and tools for simulating fundamental neurodevelopmental processes, understanding the pathology of neurological disorders, developing personalised transplantation therapies, and conducting high-throughput neurotoxicity testing.”
Microfluidic systems, also known as organ-on-chip (OoC) platforms, mimic the physical and chemical environment of human organs. These systems provide precise control over various parameters, including fluid flow, mechanical stimulation, and gas permeability, creating a more accurate in vitro model. When combined with brain organoids, these platforms make the models more physiologically relevant, which lets researchers learn more about how neurons work and how diseases work.
Professor Celiktas further elaborates: “These advancements bridge the gap between traditional two-dimensional models and the complex three-dimensional environment found in vivo. In this article, we summarise how bioengineering approaches are used to address the limitations of brain organoids in biomedical and clinical research.”
A critical advancement in this field is the integration of advanced sensors into brain organoid-on-chip platforms. These sensors enable real-time monitoring of various physiological parameters, providing detailed insights into the functioning of the brain organoids. For example, optical sensors can measure oxygen levels, while electrochemical sensors can monitor neurotransmitter activity. Additionally, microelectrode arrays (MEAs) are used to record electrophysiological activity, offering a comprehensive view of neuronal interactions and responses.
One notable study developed a multimodal midbrain organoid-on-chip model integrated with optical, electrical, and electrochemical sensors. This platform allows for non-invasive, multi-parametric monitoring, including on-chip oxygen monitoring and dopamine sensing. The use of microelectrode arrays for electrophysiological activity analysis provides valuable data on neuronal function, particularly in the context of studying Parkinson’s disease.
Professor Celiktas underscores the collaborative nature of this research: “The study is partially supported by the EU-funded OrChESTRA (Organ-on-a-chip Focused Strategic Partnership) project, where we focus on integrating advanced sensor technologies with organ-on-a-chip platforms. Coordinated by the ODTÜ MEMS Center in Turkey and partnering with IMEC in Belgium, the University of Freiburg in Germany, and Eindhoven University of Technology in the Netherlands, OrChESTRA aims to revolutionise the field by enabling the creation of more accurate and relevant models.
The integration of sensors into brain organoid-on-chip platforms has significant implications for neurotoxicity screening and disease modelling. These advanced platforms can simulate the complex interactions between different cell types in the brain, providing a more accurate representation of in vivo conditions. This capability is particularly valuable for studying the effects of toxic substances on neuronal activity and for testing the efficacy and safety of new drugs.
For instance, the ability to monitor the blood-brain barrier (BBB) integrity using impedance measurements and TEER analysis is crucial for assessing how drugs and other substances penetrate and affect the brain. Additionally, the use of patch-clamp and calcium imaging techniques allows for detailed studies of cell-specific responses, further enhancing the understanding of neurotoxic effects.
Despite the significant advancements, there are still challenges to be addressed before these technologies can be widely adopted in clinical settings. One of the primary challenges is ensuring the reproducibility and scalability of the brain organoid-on-chip platforms. Bioengineers are looking into a number of ways to make these models more consistent and durable. One idea is to create new hydrogels that look like the structures found in natural extracellular matrix (ECM).
Professor Celiktasoffers a forward-looking perspective: “We offer a comprehensive overview and future perspectives on humanised brain organoids-on-chip platforms with integrated sensors, aimed at advancing brain organoid intelligence and biocomputing studies.”
Another critical area of focus is the integration of multiple sensors into a single platform to create comprehensive, cyber-physical systems. These systems could provide continuous, real-time data on various physiological parameters, further enhancing the utility of brain organoid-on-chip platforms in preclinical and clinical research. The interdisciplinary convergence of neuroscience, bioengineering, and artificial intelligence holds great promise for advancing organoid intelligence studies and biocomputing technologies.
