Researchers from Carnegie Mellon University and Nanyang Technological University in Singapore have developed a new microfabricated sensor array that performs 3D electrophysiology of cellular organoids. Their work demonstrates that the device can be designed to wrap around small organoids and measure voltage changes across the surface of the organoids without leading to significant loss of viability of the cells. This is an exciting development that can permit more advanced scientific discovery using organoids, permit organ-on-chip bioelectronic measurements, and help quickly test new drugs for toxicity.
Various methods for studying cell electrophysiology have been developed, yet have various limitations. Patch clamp electrophysiology via micropipette is a challenging technique and difficult to perform at multiple recording sites. Voltage and calcium sensitive dyes have been incredibly valuable for scientific purposes, though are limited by photobleaching and potential toxicity. Microfabricated multielectrode arrays (MEAs) and planar field-effect transistors (FETs) are also useful, though have only been applied to 2D systems. To address these limitations, the researchers developed a new method for 3D monitoring of electrophysiology.
Using microfabrication techniques similar to those used to create computer chips, the researchers created a microfabricated electrode for 3D electrophysiology. They developed a prestressed metal/polymer multilayer structure, which naturally curls when the surface material made of germanium removed. The device is designed with 12 graphene field-effect transistors (FETs) at various sites, which interact with the organoid surface and can measure changes in cell membrane voltages. By varying the thickness of the polymer layer between two metal layers, they can control how much the electrode curls, allowing it to be customized for different sized organoids.
The researchers developed stem cell-derived cardiomyocyte organoids and performed measurements using the microfabricated 3D electrode. They were able to record for over 3 hours without substantial loss of cell viability, and detected depolarizing wave propagation across the organoid in real-time using 12-channel measurement.
Here’s a Carnegie Mellon video with Tzahi Cohen-Karni, whose lab developed the new sensor platform:
Research article in Science Advances: Organ-on-e-chip: Three-dimensional self-rolled biosensor array for electrical interrogations of human electrogenic spheroids
Via: Carnegie Mellon