It could be the world’s smallest EEG electrode, built to measure activity in a brain model the size of a pen. Its designers hope the device will help better understand neurological disorders and how potentially dangerous chemicals affect the brain.
This engineering feat, led by Johns Hopkins University researchers, is detailed today in Achievements of scienceexpands what researchers can achieve with organoids, including mini-brains — lab-grown pellets of human cells that mimic some of the brain’s structure and functionality.
“This provides an important tool for understanding the development and operation of the human brain,” said David Gracias, a chemist and biomolecular engineer at Johns Hopkins and one of the creators. “Creating micro-instruments for mini-organs is a challenging task, but this invention is fundamental to new research.”
Since organoids were created more than a decade ago, researchers have modified stem cells to create small kidneys, lungs, livers and brains. Sophisticated miniature models are used to study organ development. Researchers study intact organelles alongside genetically modified, virus-injected, and chemically-injected ones. Organoids, especially mini-brains, are becoming increasingly important in medical research because they can be used in experiments that would otherwise require human or animal testing.
But because the usual apparatus for testing organoids is flat, the researchers were only able to examine a limited number of cells on their surface. Knowing what happens to the larger number of cells in an organoid will help understand how organs function and how diseases progress, Gracias said.
“We want to get information from as many brain cells as possible so that we know the state of the cells, how they interact and their spatiotemporal electrical patterns,” he said.
Humans “are not ‘flat Stanley,'” said co-author Lena Smirnova, a research fellow in the Bloomberg School’s Division of Environmental Health and Engineering. “Planar measurements have inherent limitations.”
Inspired by electrode-dotted skull caps used to detect brain tumors, the team created tiny EEG caps for brain organoids from self-folding polymer leaflets with polymer-coated conductive metal electrodes. The microcaps cover the entire spherical shape of the organoid, allowing 3D recording from the entire surface so that, among other things, researchers can listen to the spontaneous electrical communication of neurons during drug tests.
The data is expected to be better than the current readings of conventional flat plate electrodes.
“When you record from a flat plane, you only get recordings from the bottom of a three-dimensional organoid sphere. However, an organoid is not just a uniform sphere,” said first author Qi Huang, a Ph.D. in chemical and biomolecular sciences. “There are neuronal cells that interact with each other, so we need a spatiotemporal representation of them.”
With more information from organoids, researchers can study whether chemicals used in consumer products cause problems in brain development, said co-author Thomas Hartung, director of the Center for Alternatives to Animal Testing at the Johns Hopkins Bloomberg School of Public Health.
“Certain chemicals, such as pesticides, are particularly suspect because many of them kill insects by damaging their nervous systems,” Hartung said. “Flame retardants are another class of chemicals with which we have concerns.”
The researchers hope that readings from the caps could reduce the number of animals needed to test chemical effects. Traditional testing of just one chemical requires about 1,000 rats and costs about $1 million, Hartung said. The organoid results are also more relevant, he added, because the human brain is very different from the brains of rats and mice.
Study co-authors: Bohao Tang, Julie Carolina Romero, Yuqian Yang, Gayatri Pahapale, Tian-Zhong Li, Itzi E. Morales Pantoja, Cynthia Berlinike, Terry Xiang, Mallory Salazzo and Brian S. Caffa of Johns Hopkins University, Saifeldeen Khalil Elsayed and Zhao Qin from Syracuse University, and Fang Han from the University of Washington.