Piece of Mind

Courtesy of Miro Pastrnak, Tensor Biosciences Infusing cultured brain tissue slices with the electrical activity of living brains sounds like the stuff of 1950s horror movies, or something taken straight from the pages of Mary Shelley's Frankenstein. But scientists at Irvine, Calif.-based Tensor Biosciences haven't created a monster. Their Brain-on-a-Chip™ technology promises to speed up the development of drugs for treating a variety of psychiatric disorders, including anxiety, depression, and schizophrenia. The technology is based on an instrument developed by Panasonic in the mid-1990s for recording the electrical activity of neuronal networks in a slice of living brain tissue, says Miro Pastrnak, Tensor's director of business development. The tissue is placed on a glass chip containing a two-dimensional array of 64 microelectrodes that serve a dual function: The electrodes stimulate neural network activity in the brain tissue and record electrical activity after the tissue is infused with a drug. The electrical response of various locations on the tissue is recorded with a 100-microsecond time resolution to generate a spatial map of drug effects at different sites. Tensor has increased the system's throughput by developing a 16-chip system called DS-MED, which will be used in the near-future in collaborations with pharmaceutical companies. The Brain-on-a-Chip system provides researchers with an in vitro model of the brain that mimics the behavior of living tissue. It even permits coculturing of different brain tissues so that interactions between them can be studied. Pastrnak contrasts this with currently available cell-based assays, which are not able to model complex interactions and connections between different types of neuronal cells. "The brain is just more complex than other systems, and cell-based approaches are less likely to yield reliable results than in other areas," he explains. Additionally, Tensor has developed a method to keep the tissue alive for several weeks so that long-term drug effects can be monitored; until now, brain tissue could be kept alive for only several hours, limiting the ability of tissue-based assays to monitor the effects of drugs that can take weeks to produce effects in patients. And, brain tissue-based assays are generally performed on tissue slices that do not produce their own electrical activities and require high concentrations of a drug to produce signals. Tensor has developed methods to manipulate cultured brain tissue to produce beta, gamma, and theta electroencephalographic waves, allowing drugs to be studied at clinical dosage levels. Courtesy of Miro Pastrnak, Tensor Biosciences BRAIN BLAST! Cultured rat hippo-campal tissue on a chip. The 64 microelectrode array is 1.0 x 1.0 mm in size and the tissue slice is 350 microns thick. Pastrnak says Tensor's technology fills an unmet need in central nervous system (CNS) research, as it not only offers a more representative in vitro model of the brain than cell-based screening, but also is ultimately more predictive than behavioral assays. "We're really bridging a gap between cell-based and behavioral approaches in CNS drug discovery, and generating a lot more physiologically relevant information about the drug candidates so that the right lead compounds can be selected for development," he says. The MED64 system, the backbone of Brain-on-a-Chip technology, is already in place in a number of neuroscience laboratories. Amy Arai, assistant professor of pharmacology, Southern Illinois University, uses the system to study long-term drug effects in tissue slices from the cerebellum. Arai says that such long-term studies are possible because the system allows brain tissue to be cultured directly on the electrode, where it lives for up to three months, unlike conventional electrophysiological methods that would allow activity to be recorded over only a day. Arai's laboratory is currently exploring the system's diagnostic potential, using it to detect abnormal activity in animal tissue after exposure to serum from a patient with a cancer-related neurological disorder. Tensor Biosciences plans to use the more advanced DS-MED system as part of a three-step, integrated drug-discovery platform comprising three components: a cell-based, LaserPatch technology that mimics the interaction of a neurotransmitter with a cell in a synapse; a tissue-based assay (Brain-on-a-Chip); and a behavioral assay using a wireless, multi-electrode, in vivo probe. Says Pastrnak: "We believe that a combination of three technologies at different levels of analysis--cells, tissues, and animals--which approximate better the living system and particularly human behavior, will enable scientists to identify better drug candidates that are more likely to succeed in clinical trials." --Aileen Constans

Piece of Mind

Interested in reading more?

Become a Member of