by Ten years ago, neuroscientist Sergiu Pasca embarked on a journey to revolutionize brain organoid research. Pasca, whose lab was just starting to take shape, envisioned a novel technique for growing 3D clusters of human brain cells in Petri dishes. These clusters, known as brain organoids, had the potential to provide valuable insights into brain development and the drivers behind conditions like autism and epilepsy. However, Pasca knew that the true challenge lay in precisely probing and manipulating these complex structures.
It was during a chance encounter at a café that Pasca crossed paths with chemist Bianxiao Cui, an expert in designing devices to record the electrical activity of neurons. Intrigued by Pasca’s as-yet-unpublished organoid research, Cui joined forces with him to tackle the problem at hand – how to record from free-floating clusters of neurons throughout their months-long development without disrupting their structure and electrical connections.
Over the course of a decade, Pasca, Cui, and their team explored various approaches to solve this challenge. Inspired by kirigami, an art form similar to origami that involves cutting and folding paper to create intricate sculptures, they developed a groundbreaking technique. This technique was recently published in the prestigious journal Nature Biotechnology, with the study led by Wu Tsai Neuro Interdisciplinary Postdoctoral Scholar Xiao Yang and Cui lab postdoc Csaba Forro.
The collaboration between Pasca and Cui was made possible by the proximity of their respective departments at Stanford University’s James H Clark Center, home to the Wu Tsai Neurosciences Institute. The supportive environment and the convergence of expertise in the area allowed them to work together seamlessly, despite their different backgrounds as a chemist and a physician-scientist.
Traditional methods of recording brain activity were unsuitable for brain organoid research. These methods were designed for living animals or cells on a fixed surface, whereas organoids float freely in fluid. Being much smaller than an entire brain, organoids are highly vulnerable to damage caused by recording devices. Slicing the organoids in half and placing the cut edge on an electrically conductive surface was a common approach, but it had its downsides. Within a few days, the organoids lost their free-floating nature and unique properties, eventually resembling pancakes.
The kirigami-inspired electrodes developed by Pasca, Cui, and their team offered a groundbreaking solution to this problem. By carefully shaping and folding the electrodes, they were able to conform to the delicate structure of brain organoids without causing damage. This allowed for precise recording and manipulation of the organoids’ electrical activity throughout their development.
The implications of this breakthrough are significant. With the ability to study brain organoids more effectively, scientists can gain deeper insights into the intricate processes of brain development. This knowledge has the potential to revolutionize our understanding of conditions such as autism and epilepsy, enabling the development of more targeted and effective treatments.
The success of this groundbreaking technique highlights the power of collaboration and interdisciplinary research. Pasca and Cui’s chance encounter and subsequent collaboration demonstrate the importance of bringing together experts from diverse fields to overcome complex challenges. The future of brain organoid research is bright, thanks to the innovative and collaborative efforts of scientists like Pasca and Cui.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
