Brain-on-a-Chip: Another One of the Organ-on-a-Chip Inventions

Bioengineering has rapidly evolved in the past decade, with novel technologies constantly introduced to study challenging subjects. A product of this era of rapid technological evolution, the “brain-on-a-chip” device was created in 2018 by scientists of Lawrence Livermore National Laboratory (LLNL) in an attempt to determine the effects of chemicals, biological agents, disease, and pharmaceutical drugs on the brain. This device overrides any need for human or animal subjects, making its fabrication particularly significant for future neuroscience research. The complex neuronal plasticity and diverse cellular interaction of the human brain have previously obstructed the creation of an efficient brain-on-a-chip device, making LLNL’s research all the more impressive in its field.

The device is essentially a wafer of semiconductors connected to a network of nanowires. To stimulate the central nervous system, the chip records neural activity from multiple brain cell types deposited and grown onto microelectrode arrays. The nanowires create functional neuronal circuits that represent the interconnectivity of neurons. The platform is a result of the lab’s in-vitro Chip-Based Human Investigation Platform project, or iCHIP. It is expected to increase understanding of how brain cells interact and combat disorders and to determine how exposure to chemical and biological weapons impacts the human mind.

The chip is divided into four sections — three sub-regions and an external region representing the brain’s cortex — to best imitate the areas of the brain. Researchers then positioned primary hippocampal and cortical cells onto the electrodes corresponding to their orientation in the brain. To execute this feat, the scientists used custom-fabricated inserts that were removed after the cell placement to allow free interaction and communication within the regions. The electrical energy emitted by cells during communication, known as action potential patterns, were monitored over time. With this device, scientists hope to better understand the networks formed among various regions of the brain using only human-relevant data and without any animal testing.

The device’s resultant data is meant to provide a more applicable model of how certain types of neurons react to chemical exposure and predict human response to countermeasures. Stated iCHIP co-lead author and LLNL research engineer Dave Soscia, “While we’re not close to the point where we can fully recapitulate a brain outside of the body, this is an important step in terms of increasing complexity of these devices and moving in the right direction. The idea is that eventually the community gets to a point where people are confident enough in the devices that the effects they see from putting chemicals or pharmaceutical drugs into the platform environment are similar to the results we would see in the human body.”

The technology also reveals how cells communicate in diverging ways when combined with or in close proximity to different cell types. Because the microscale, funnel-shaped insert does not require patterning its surface with different chemicals for cell adherence, it allows for the insert to be utilized on a variety of chip-platforms and cell types. “Here you literally just put an insert in, pipette the cells through the top of the insert, and it deposits them with precision onto specific regions on the electrode array. And because it’s removable, the cells adhere but they have nothing holding them back; they’re allowed to grow freely and communicate with the other regions,” added Soscia. “It was very important to us that we didn’t have physical barriers, so the cells could grow processes to interact and communicate.”

The “brain-on-a-chip” phenomenon began with researchers at Harvard’s School of Engineering and Applied Sciences in 2017 creating a device that indicated the communication differences between neurons coming from different parts of the brain. LLNL’s work represents the most recent application of the technology in studying the impact of long-term exposure to biological and chemical agents. In the future, LLNL will continue chip-based research as part of a strategic initiative focused on the brain under principal investigator Nick Fischer. Researchers aim to incorporate brain and blood-brain barrier chip platforms and eventually expand the ‘brain on a chip device’ to three-dimensions. To fully analyze and model the novel device’s data, the researchers hope to connect with computer-scientists and statisticians—and truly understand their extraordinary results.

References

“Brain-on-a-chip” to test effects of biological and chemical agents, develop countermeasures. (2017, December 18). Retrieved from https://www.sciencedaily.com/releases/2017/12/171218092556.htm

P. (2018, January 15). “Brain-on-a-chip” devices are changing how we study the brain. Retrieved from https://futurism.com/brain-chip-devices-changing-how-study-brain

Meet Chip: Brain. (2018, March 30). Retrieved from https://ncats.nih.gov/tissuechip/chip/brain