Lawrence Livermore scientists and engineers have developed an in vitro “brain-on-a-chip” device for testing and predicting the long-term effects of biological and chemical agents, disease, or pharmaceuticals on the brain. The device, part of the Laboratory’s iCHIP (in vitro chip-based human investigational platform) project, simulates the central nervous system by recording neural activity from multiple brain cell types deposited and grown onto microelectrode arrays. The results were published in the November 21, 2017, edition of PLOS ONE.
To re-create the structural anatomy of the brain, researchers divided the chip into four distinct areas—an inner region further split into three subregions and an outer region representing the brain’s cortex. They deposited primary hippocampal and cortical cells onto the inner and outer regions’ electrodes, and then monitored the “bursts” of electrical potential that cells emit when communicating and observed how the cells interacted over time. The researchers also successfully performed tests with a four-cell insert to prove more cell types could be used simultaneously. “While we cannot fully recapitulate a brain outside of the body, this work is an important step in terms of increasing complexity of these devices and moving in the right direction,” said co-lead author and Laboratory engineer Dave Soscia.
Scientists say the platform is part of the Laboratory’s broader vision for countering emerging and existing threats. It allows them to study the networks formed among various regions of the brain, and obtain timely, human-relevant data without animal or human testing. With the brain-on-a-chip platform, researchers could analyze how disease spreads through the organ, model epilepsy and other neurological disorders, or examine the effects of chemical or biological exposure over several months.
Contact: David Soscia (925) 423-8949 (soscia1@llnl.gov).
Ann Arbor, Michigan–based EVOQ Therapeutics has licensed the Laboratory’s nanolipoprotein (NLP) technology for cancer immunotherapy, which deploys the body’s own immune system to fight cancer. Developed by Livermore biomedical researchers over the last decade with funds from the Laboratory Directed Research and Development Program, NLPs are water-soluble molecules that are 6 to 30 billionths of a meter in size and resemble high-density lipoproteins (HDL), known as “good cholesterol” in humans. EVOQ is developing a vaccine delivery platform that uses synthetic HDL.
Checkpoint inhibitors, which block normal proteins on cancer cells, are one immunotherapy approach that holds promise in the cancer treatment community. Although inhibitors have only been successful in 20 to 40 percent of cases, research using animal models has shown that when the synthetic HDL delivery is combined with the approach, complete tumor regression is exhibited in about 85 percent of colon carcinoma and melanoma cases. Ideally, synthetic peptides, small fragments of neoantigen proteins, would be incorporated into NLPs along with adjuvants (molecules that activate the patient’s immune system). NLPs would then enter the body’s lymph nodes, activating T-cells that circulate throughout the body and destroy the cancerous tumor cells.
NLPs were initially developed between 2005 and 2008 by a team of Livermore scientists led by Paul Hoeprich. In addition to the use of NLPs for transporting cancer vaccines, Lawrence Livermore scientists continue exploring other applications for the technology. These research areas include developing vaccines for influenza and chlamydia, formulating drug molecules to enhance NLP efficacy, and shuttling therapeutics across the blood–brain barrier.
Contact: Paul Hoeprich (925) 422-7363 (hoeprich2@llnl.gov).
Surfactants, also known as detergents, are used extensively in the cosmetics, oil, food, agriculture, healthcare, and pharmaceutical industries. However, the majority of surfactants are petrochemicals, which can have a negative impact on the environment and increase the nation’s dependence on foreign and domestic oil. With the demand for biosurfactants—those produced from microorganisms—on the rise, scientists at Lawrence Livermore have begun studying a new “tunable” kind that is environmentally friendly and can have broad industrial utility. The research appeared in the January 2, 2018, edition of PLOS ONE.
The new Laboratory surfactant is derived from the red yeast Rhodotorula and is composed of a linear carbohydrate connected to a fatty acid. “The primary challenge is that microorganisms produce biosurfactants as a complex mixture of closely related surfactants, not a pure, single type of compound,” says Matt Lyman, a Livermore biologist and lead author of the paper. “If we can harness the surfactant diversity found in nature and provide it in a pure form that is ‘tunable’ for industry needs, then it becomes a powerful technology beyond what exists today for commercial biosurfactants.” The research was conducted through a collaboration between the Laboratory’s Biosciences and Biotechnology Division and the Forensic Science Center.
The goal of the Livermore team is to use Rhodotorula as a “microbial factory” to produce a base surfactant compound at minimal cost. The team will then perform routine chemical modifications to enable it to slide up and down the hydrophilic–lipophilic balance (HLB) scale, which determines whether a surfactant has more of an affinity toward water or oil. Such a system would provide a “made-to-order” biosurfactant with a specific HLB most useful to customers and their applications.
Contact: Matt Lyman (925) 424-2039 (lyman2@llnl.gov).