Author Jeff Brown created the character (and book series) Flat Stanley when his son joked that he thought the bulletin board above his bed would fall on him and flatten him in his sleep. Of course, that can’t happen, so while Flat Stanley is a beloved fictional character, he’s not representative of the human population. Why then are scientists forced to test mini-versions of human organs grown in the lab on flat surfaces?
Engineers at Johns Hopkins University have now changed that with the development of the world’s smallest EEG electrode cap – about the size of a pen point – created to measure activity in a brain organoid. Scientists expect the device to lead to a 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 for further research,” said co-creator David Gracias, a chemical and biomolecular engineer at Johns Hopkins. “This provides an important tool for understanding the development and functioning of the human brain.”
Scientists and researchers have flocked to organoids since their inception over a decade ago. The intricate miniature models are used to examine the development of organs – and everything from kidneys to lungs to liver to brain has been studied by researchers.
Brain organoids are particularly important in medical research because they can be used in experiments that would be both practically and ethically impossible in human testing.
But because the conventional apparatus for testing organoids is flat, researchers have only been able to examine cells limited to 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, who holds 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 neuronal cells that communicate with each other, which is why we need a spatio-temporal mapping of them.
Inspired by electrode skull caps used to detect brain tumors, Huang and his research team created tiny EEG capsules for brain organoids from “self-folding polymer leaflets with conductive polymer-coated metal electrodes”, according to the article published in Scientists progress. The microcapsules wrap around the spherical shape of an organoid, allowing 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 of chemicals like pesticides and flame retardants on brain development.
This development comes at a good time as there has been renewed attention to the adverse health effects associated with per- and polyfluoroalkyl substances (PFAS), also known as forever chemicals. These eternal chemicals are found basically everywhere, including drinking water, soil, air, food, and materials in homes and work spaces. Calling PFAS substances an “urgent public health and environmental concern,” the EPA created a roadmap until 2024 derived from three tenants: search, restriction and remediation.
Johns Hopkins researchers also see their tiny EEG caps for brain organoids as a way to reduce animal testing. Traditional tests of a single chemical require around 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.