Kirigami electrodes unfold new horizons for brain organoid research

Already, Pasca was confident that these organoids and more complex "assembloids," which mimic many aspects of the growth and maturation of human brain circuits, would soon let scientists study brain development more precisely than ever before, enabling new insights into the early drivers of conditions like autism or epilepsy.

Realizing that potential, however, was a daunting challenge.

"As we began building neural tissues that were ever-more complex, the main limitation was not how we make them, but actually how we're going to precisely probe and manipulate them," said Pasca, now the Kenneth T. Norris, Jr. II Professor of Psychiatry and Behavioral Sciences.

That's when he ran into chemist Bianxiao Cui at a cafe at the James H Clark Center, which sits between the Stanford School of Medicine and the University's chemistry and biology buildings and was then the home of the Wu Tsai Neurosciences Institute. Cui is an expert at designing unusual devices and approaches to record the electrical activity of neurons and other cells. They sat down together, and Pasca told Cui about his as-yet-unpublished research.

"That was amazing and quite eye-opening," said Cui, the Job and Gertrud Tamaki Professor in the Department of Chemistry. The problem Pasca presented was intriguing: how to record from free-floating clusters of neurons over their months-long development, without catastrophically disrupting their structure and electrical connections.

Cui lab and Pasca lab. Credit: Stanford University

Top view of a Kirigami electrode mesh. Credit: Cui lab and Pasca lab

3D rendering of of a flat kirigami electrode array expanding into 3D "cradle" to support and study the development of human brain organoids and assembloids. Credit: Cui lab and Pasca lab