A brain organoid shown in green, encapsulated in a blue shell electrodes device. Credit: Qi Huang, Gayatri Pahapale, Gracias lab, Johns Hopkins University
Author Jeff Brown created the character (and book series) Flat Stanley when his son joked that he thought the bulletin board over his bed would fall on him and flatten him in his sleep. Of course, that can’t happen, so while Flat Stanley may be a beloved fictional character, he’s not representative of the human population. Why then are scientists forced to test mini, lab-grown versions of human organs on flat surfaces?
Engineers from Johns Hopkins University have now changed that with the development of the world’s tiniest EEG electrode cap—about the size of a pen dot—created to measure activity in a brain organoid. The scientists expect the device to lead to better understanding of neural disorders, and shed light on the health effects of potentially dangerous chemicals.
“Creating micro-instrumentation for mini-organs is a challenge, but this invention is fundamental to new research,” said co-creator David Gracias, a Johns Hopkins chemical and biomolecular engineer. “This provides an important tool to understand the development and workings of the human brain.”
Scientists and researchers have flocked to organoids since they were first created more than a decade ago. The complex, miniature models are used to examine how organs develop—and everything from kidneys to lungs, livers and brains have been studied by researchers.
Brain organoids are particularly important in medical research since they can be used in experiments that would be both practically and ethically impossible in human testing.
But because the conventional apparatus to test organoids is flat, researchers have only been able to examine limited cells on their surface—until now.
“If you record from a flat plane, you only get recordings from the bottom of a 3D organoid sphere,” said Qi Huang, a Ph.D. candidate in chemical and biomolecular engineering, and first author of the new study. “However, the organoid is not just a homogeneous sphere. There are neuron cells that communicate with each other—that's why we need a spatial-temporal mapping of it.”
Inspired by the electrode-dotted skull caps used to detect brain tumors, Huang and his research team created tiny EEG caps for brain organoids from “self-folding polymer leaflets with conductive polymer-coated metal electrodes,” according to the paper published in Science Advances. The microcaps wrap around an organoid’s spherical shape, enabling 3D recording from the entire surface—not just a handful of cells.
The researchers say this allows them to listen to the spontaneous electrical communication of neurons during drug tests. For example, with this level of detail, they can study the effects chemicals like pesticides and flame retardants have on the development of the brain.
The development is timely as there has been renewed focus on the adverse health effects linked to per- and polyfluoroalkyl substances (PFAS), also called forever chemicals. These forever chemicals are found essentially everywhere, including drinking water, soil, air, food and materials in homes and workspaces. Calling PFAS substances an “urgent public health and environmental issue,” the EPA has created a roadmap through 2024 derived from three tenants: research, restriction and remediation.
The Johns Hopkins researchers also see their tiny EEG caps for brain organoids as a way to reduce animal testing. Traditional testing of just one chemical requires about 1,000 rats and can cost up to $1 million. Not only would the tiny EEG caps be more cost-effective, the study authors say, but they would also provide more accurate results by eliminating interspecies differences between humans and animal models.