Novel three-dimensional, conformal microelectrode arrays for interrogating and manipulating three-dimensional cell culture systems

Background:

Three-dimensional (3D) cell culture systems, such as organoids and spheroids, have emerged as powerful tools in biomedical research, drug discovery, and personalized medicine. Unlike traditional two-dimensional (2D) cultures, 3D systems more accurately mimic the complex architecture and microenvironment of human tissues, enabling more physiologically relevant studies of development, disease, and therapeutic response. As these models become increasingly sophisticated, there is a growing demand for advanced technologies capable of probing and manipulating their electrical activity, particularly in fields such as neuroscience, cardiology, and tissue engineering. High-resolution, non-destructive electrophysiological monitoring is essential for understanding functional properties, disease mechanisms, and drug effects in these complex biological systems. Despite the promise of 3D cell cultures, current approaches to electrophysiological interrogation are limited by the use of planar microelectrode arrays (MEAs), which can only interface with the surface of these volumetric tissues. This constraint results in poor spatial coverage and limited access to the inner regions of the culture, significantly reducing the accuracy and comprehensiveness of electrical recordings and stimulations. Planar MEAs are unable to conform to the intricate shapes of organoids, leading to inconsistent contact and signal quality, and often necessitating invasive or destructive methods to access deeper layers. These limitations hinder the ability to fully characterize and manipulate the functional properties of 3D cultures, impeding progress in research and the development of new therapies.

Technology Overview:

The technology is a biocompatible, conformal microelectrode array (MEA) specifically engineered for 3D cell culture systems, such as organoids. Constructed from multiple layers of polymeric materials, the MEA self-assembles into a flexible 3D structure that can wrap around complex cell cultures. The MEA integrates with a custom printed circuit board and connects to a headstage, transmitting high-fidelity electrophysiological data. This configuration allows for comprehensive electrical interrogation and manipulation of 3D cultures by providing increased and distributed contact points, a significant improvement over traditional planar MEAs. What differentiates this technology is its ability to conformally interface with the entire surface of 3D cell cultures, overcoming the inherent limitations of planar MEAs that only contact cells at the culture’s surface. The self-assembling, flexible structure maximizes electrode coverage and contact quality, enabling more accurate and holistic measurement and stimulation of electrically active tissues. This approach opens new possibilities for drug testing, personalized medicine, and advanced research into neurodegeneration and tissue engineering, offering a scalable, high-resolution solution for the electrophysiological analysis of complex 3D biological systems.

Advantages:

•    Enables comprehensive and distributed electrical interrogation of 3D cell cultures by conformally wrapping around organoids
•    Improves biocompatibility and electrical performance.
•    Flexible, multilayer polymer structure allows self-assembly into a 3D shape suited for complex tissue geometries
•    Overcomes limitations of planar MEAs by increasing contact points and coverage area on 3D tissues
•    Facilitates high-fidelity electrophysiological recordings via integration  with commercial recording technologies
•    Supports advanced applications in drug testing, personalized medicine, neurodegeneration research, and tissue engineering
•    Scalable and manufacturable using photolithography and polymer microfabrication techniques

Applications:

•    High-throughput drug screening platforms
•    Personalized medicine organoid analysis
•    Neurodegenerative disease modeling
•    Cardiac tissue electrophysiology studies
•    Bioelectronic device development

Intellectual Property Summary:

Patent application filed

Stage of Development:

•    TRL 4
•    https://en.wikipedia.org/wiki/Technology_readiness_level

Licensing Status:

This technology is available for licensing.