Lawrence Livermore National Laboratory

Anantha Krishnan

Anantha Krishnan

Associate Director for Engineering

At the Intersection of Engineering, Neurobiology, and Computation

LAWRENCE Livermore has been at the forefront of many recent advances in innovative measurement methodologies and engineering platforms as well as computational models to elucidate critical aspects of neurobiology. As part of the Laboratory’s mission of enhancing national security, one focus has been protecting warfighters who may be exposed to a multitude of advanced and even outlawed weapons, such as chemical and biological agents. As the feature article, Small Brain-on-a-Chip Promises Big Payoffs describes, the Laboratory has developed a new “brain-on-a-chip” platform—a remarkable device the size of a microscope slide—that mirrors the structure and functions of human brain tissues. The motivation for this innovative technology is to improve our scientific understanding of the human neural system and how it responds to exposure to toxic compounds.

Obviously, the effects of chemical weapons, even at low doses, cannot be tested on human subjects. Moreover, testing on animals has proven to be unreliable in reproducing the human physiological response, as can be seen in pharmaceutical development. Producing a reliable model that accurately recapitulates the function of the human brain is a formidable challenge. Livermore’s brain-on-a-chip is a promising solution, offering an advanced tissue model that incorporates the three-dimensional architecture of the neural system, the in vivo heterogeneity of cell and tissue types, and sensing modalities to observe neuronal function with high spatial and temporal resolution.

To realize the brain-on-a-chip, Livermore researchers devised a unique approach wherein they can precisely deposit different types of neuronal cells onto submillimeter regions of a multielectrode array embedded in a biocompatible chip a few centimeters long. Over time, the cells establish intricate networks and begin to communicate with one another. The embedded microelectrode arrays, which were fabricated at the Laboratory’s Center for Micro and Nanotechnology, allow researchers to record these cellular communications. The brain-on-a-chip device can also be connected to a Livermore-developed blood–brain barrier designed to mimic the one found in the human brain, further improving the technology’s efficacy.

Livermore’s strong expertise in data analytics and statistical modeling is helping to process the vast information sent back and forth from neuron to neuron. By accurately recording these signals, the brain-on-a-chip is enhancing scientists’ knowledge of how neurons process information and respond to compounds and environmental factors. Importantly, the measurements and data obtained from the device are being validated, including by exposure to select toxic chemicals in tests conducted at Livermore’s Forensic Science Center.

Both the brain-on-a-chip and the associated blood–brain barrier are elements of Livermore’s iCHIP (in vitro chip-based human investigational platform) project that aims to better understand and eventually predict the effects of pharmaceutical drugs as well as potentially harmful substances on human cells, tissues, and organs without the need for animal or human test subjects. Other subsystems of the iCHIP have included a platform with cultured heart cells and one with neurons comprising the peripheral nervous system.

For the warfighter, the brain-on-a-chip will potentially accelerate the development of effective countermeasures for exposure to chemical and biological agents. Down the road, the device may also provide a way to significantly speed up development of new pharmaceuticals—a process that now takes many years and several billions of dollars to accomplish. Indeed, Lawrence Livermore’s unique multidisciplinary research focus, especially at the intersection of engineering, neurobiology, and computation, will continue to make important advances in enhancing the protection of the nation’s warfighters—and its everyday citizens.