In recent years, the use of organoids has emerged as a transformative tool in biomedical research, offering three-dimensional, physiologically relevant models of human tissues. Among the many applications of organoids, their use in electrophysiology is gaining traction, particularly in the pharmaceutical and biotech industries. By harnessing organoid electrophysiology, companies can enhance drug discovery and preclinical testing, leading to more effective and safer therapeutics.

The Role of Organoids in Industry

Pharmaceutical and biotech companies are increasingly utilizing organoid models to replicate human organ functions, providing a    better platform for studying diseases and screening drug candidates than comparable animal models. Organoids derived from induced pluripotent stem cells (iPSCs) or patient-derived tissues offer key advantages, including genetic fidelity, structural complexity, and the ability to mimic organ-specific electrophysiological properties.

Advantages of Organoid Electrophysiology

Electrophysiology, the study of electrical properties in biological tissues, is particularly important for drug development in areas such as neuroscience and cardiology. By incorporating electrophysiological techniques into organoid models, companies can:

• Improve Drug Screening: Organoids with functional ion channels and neural networks enable high-throughput screening of neuroactive and cardiotoxic drugs.
• Enhance Disease Modeling: Electrophysiological assessments help replicate pathological conditions such as epilepsy, cardiac arrhythmias, and neurodegenerative diseases.
• Reduce Reliance on Animal Models: Organoid systems provide a human-relevant alternative to traditional animal studies, improving translational accuracy.

Applications in Pharmaceutical and Biotech Sectors

Neurological Disorders and Drug Discovery

Companies developing treatments for neurological conditions, including Alzheimer's disease, Parkinson's disease, and epilepsy, leverage brain organoids to study neuronal activity and synaptic function. Using techniques such as microelectrode arrays (also called “multielectrode arrays” or “MEAs”) and patch-clamp electrophysiology, researchers can observe how neurons respond to different compounds, improving candidate selection for clinical trials.

Example: Some biotech companies utilize brain organoids combined with electrophysiological assessments to test drug efficacy and toxicity in models that closely resemble human neural tissue.

Figure 1. Human brain organoids cultured on Mesh MEA for electrophysiological recordings. Images courtesy of Jenny Hsieh’s lab at the University of Texas at San Antonio studying human brain organoids displaying an epileptic model (organoids cultured and microscopic images by Sara Mirsadeghi).

Figure 2. Neural spheroid on a Mesh MEA. Traces (top right) were recorded from four electrodes contacted by the spheroid, and spikes (bottom right) were identified using a 6-sigma threshold. Data and images courtesy of Tom Stumpp and Dr. Peter Jones at the NMI Natural and Medical Sciences Institute in Reutlingen, Germany.

Cardiac Drug Development

Cardiac organoids integrated with electrophysiological monitoring allow researchers to assess the impact of drugs on heart rhythms and ion channel function. Such models are crucial for evaluating proarrhythmic risks associated with new pharmaceuticals.

Example: Some organizations are employing engineered heart tissues (EHTs) and cardiac organoids to predict drug-induced cardiotoxicity, reducing the likelihood of adverse cardiac events in patients.

Drug Screening with Mesh MEA and IntraCell

Cardiac organoids self-organize, even forming chambers in some cases, providing a physiologically relevant model for studying drug effects and cardiac pathophysiology compared to 2D cultures.  Mesh MEAs allow one to electrically measure the coordinated activity and signal propagation within the organoid. 

Cardiac organoids offer a unique opportunity for studying reverse effects of drugs or inducing disease states.  Intracellular action potential data can be recorded from inside the organoid using IntraCell’s laser-based optoporation technology, and extracellular field potentials can be recorded from inside the organoid using Mesh MEA, which preserves the organoid’s shape while collecting true-to-life data.  As both IntraCell and Mesh MEA collect data without damaging the organoid, the organoid can be kept alive for extended periods of time, meaning that both acute and long-term studies can be conducted using these systems.  

Challenges and Future Prospects

Despite the promise of organoid electrophysiology, several challenges remain:

• Scalability: Standardizing organoid production for high-throughput applications remains a hurdle.
• Complexity: Reproducing full organ functionality, including vascularization and immune interactions, is still an ongoing challenge.
• Data Interpretation: Electrophysiology can generate large data sets to analyze. Advanced analysis and AI analytics can help overcome this challenge. 

As technological advancements continue, the integration of organoids with bioelectronic systems, artificial intelligence, and lab-on-a-chip platforms will further enhance drug discovery and personalized medicine approaches.

Organoid electrophysiology is revolutionizing drug discovery by providing human-relevant models for testing and research. Pharmaceutical and biotech companies leveraging this technology stand to improve drug efficacy, reduce development costs, and accelerate the delivery of life-saving treatments. As the field continues to evolve, organoid-based platforms will play an increasingly vital role in shaping the future of precision medicine and disease modeling.