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Dyes detect disease through heartbeat signals

University of Connecticut Health News Aug 30, 2017

Vibrant tones of yellow, orange, and red move in waves across the screen. Although the display looks like psychedelic art, it’s actually providing highly technical medical information – the electrical activity of a beating heart stained with voltage–sensitive dyes to test for injury or disease.

These voltage–sensitive dyes were developed and patented by UConn Health researchers, who have now embarked on commercializing their product for industry as well as academic use.

Electrical signals or voltages are fundamental in the natural function of brain and heart tissue, and disrupted electrical signaling can be a cause or consequence of injury or disease. Directly measuring electrical activity of the membranes with electrodes isn’t possible for drug screening or diagnostic imaging because of their tiny size. In order to make the electrical potential visible, researchers use fluorescent voltage sensors, also known as voltage–sensitive dyes or VSDs, that make cells, tissues, or whole organs light up and allows them to be measured with microscopes.

Not all dyes respond to voltage changes in the same way, and there is a common trade–off between their sensitivity and speed. Slower dyes can be used for drug screening with high sensitivity, but they can’t measure the characteristics of rapid action potentials in some tissues, like cardiac cells. Fast dyes can be used to image action potentials, but they require expensive, customized instrumentation, and are not sensitive enough for crystal clear results on individual cells.

Professor of cell biology and director of UConn’s Center for Cell Analysis & Modeling, Leslie Loew and his team have developed new fast dyes that are also highly sensitive, eliminating the speed/sensitivity trade–off.

Loew and research associates Corey Acker and Ping Yan have devoted much of their careers to developing and characterizing fluorescent probes of membrane potential like voltage–sensitive dyes. The team has even been providing their patented fast dyes to fellow researchers for the past 30 years, but they only recently became interested in commercializing their work.

To learn more about the science of entrepreneurship, they took advantage of several of UConn’s homegrown programs. Loew and Acker’s first step into entrepreneurship began in the fall of 2016, when they were accepted into UConn’s National Science Foundation (NSF) I–Corps site, Accelerate UConn. They credit the program with giving them a solid foundation to evaluate their technology and business strategy.

Launched in 2015, Accelerate UConn aims to successfully advance more university technologies along the commercialization continuum. Under the auspices of the Office of the Vice President for Research and the Connecticut Center for Entrepreneurship and Innovation (CCEI), Accelerate UConn provides participants with small seed grants and comprehensive entrepreneurial training.

The dyes that Loew, Acker, and Yan develop will also allow drug companies to respond to new cardiac safety screening regulations from the Food and Drug Administration called CiPA (the Comprehensive in vitro Proarrythmia Assay).
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