Engineering feat expands what researchers can accomplish with organoids


It could be the world’s smallest EEG electrode cap, created to measure activity in a brain model the size of a pen point. Its designers expect the device to lead to a better understanding of neural disorders and how potentially dangerous chemicals affect the brain.

This technical feat, led by researchers at Johns Hopkins University and detailed today in Scientists progressexpands what researchers can accomplish with organoids, including mini-brains – lab-grown balls of human cells that mimic some of the structure and functionality of a brain.

“It provides an important tool for understanding the development and functioning of the human brain,” said David Gracias, chemical and biomolecular engineer at Johns Hopkins and one of the creators. “Creating micro-instrumentation for mini-organisms is a challenge, but this invention is fundamental for further research.”

Since the creation of organoids more than a decade ago, researchers have modified stem cells to create small-scale kidneys, lungs, livers and brains. The complex miniature models are used to study the development of organs. Researchers are studying unmodified organoids alongside those that are genetically modified, injected with viruses and exposed to chemicals. Organoids, especially mini-brains, are increasingly important in medical research because they can be used in experiments that would otherwise require testing in humans or animals.

But because the conventional apparatus for testing organoids is flat, the researchers were only able to examine cells limited to their surface. Knowing what happens to more cells in the organoid would help understand organ function and disease progression, Gracias said.

“We want to get information from as many cells as possible in the brain, so that we know the state of the cells, how they communicate, and their spatio-temporal electrical patterns,” he said.

Humans “are not ‘Flat Stanley,'” said co-author Lena Smirnova, a research associate in the Bloomberg School’s Department of Environmental Health and Engineering. “Flat measurements have inherent limitations.”

Inspired by electrode skull caps used to detect brain tumors, the team created tiny EEG caps for brain organoids from self-folding polymer sheets with conductive polymer-coated metal electrodes. The microcapsules envelop the entire spherical shape of an organoid, allowing 3D recording of the entire surface so that, among other things, researchers can listen to the spontaneous electrical communication of neurons during drug testing.

The data should be greater than current readings from conventional electrodes on a flat plate.

“If you record from a flat plane, you only get recordings from the bottom of a 3D organoid sphere. However, the organoid is not just a homogeneous sphere,” said first author Qi Huang. , PhD candidate in chemical and biomolecular engineering. “There are neuronal cells that communicate with each other, which is why we need spatio-temporal mapping.”

With more detailed information about organoids, researchers can study whether chemicals used in consumer products cause brain development problems, 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 like pesticides are particularly suspect because many kill insects by damaging their nervous systems,” Hartung said. “Flame retardants are another class of chemicals that we are concerned about.”

The researchers hope the cap readings could reduce the number of animals needed to test for chemical effects. Traditional single-chemical tests require about 1,000 rats and cost about $1 million, Hartung said. Organoid results are also more relevant, he added, because human brains are very different from rat and mouse brains.

Study co-authors include Bohao Tang, July Carolina Romero, Yuqian Yang, Gayatri Pahapale, Tien-Jung Lee, Itzy E. Morales Pantoja, Cynthia Berlinicke, Terry Xiang, Mallory Solazzo, and Brian S. Caffo of the University Johns Hopkins, Saifeldeen Khalil Elsayed and Zhao Qin of Syracuse University, and Fang Han of the University of Washington.


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