Potentiometric Probes, a biotech company created by UConn Health researchers, has been awarded a $1.9 million Small Business Innovative Research (SBIR) grant by the National Institutes of Health (NIH) to commercialize their voltage-sensitive dyes for academic and industry use.
Originally developed at UConn Health by professor Les Loew and assistant professors of cell biology Corey Acker and Ping Yan, these voltage-sensitive dyes are the product of three decades of research. Through the staining of cells, tissues, and organs, the voltage-sensitive dyes convert changes in voltage across cell membranes into visible changes in fluorescence, allowing researchers to study electrical activity.
Traditional methods used to study electrical activity of cells have involved puncturing individual cell membranes with electrodes, allowing researchers to measure the voltage difference between the inside and outside of the cell. But, each electrode has to be positioned in the right place to puncture each individual cell, limiting the number of cells that can be studied simultaneously.
With voltage-sensitive dyes, researchers can stain an entire tissue and use a camera to measure patterns of electrical activity across a massive number of cells, surpassing this limitation.
“Each pixel in the camera effectively amounts to a single electrode,” says Loew. “So you can use millions of pixels to get millions of individual recordings from cells or subcellular regions like dendrites or axons or synaptic connections.”
The applications of these voltage-sensitive dyes are far-reaching, offering a gateway to a deeper understanding of both the brain and the heart. From studying neurological disorders like epilepsy to understanding cardiac function, the dye can literally and figuratively shed light on what’s happening in the cell when electrical signals are disrupted.
For example, in epilepsy research, overactivity of specific brain cells called neurons generates an abnormal surge of electrical impulses that can effectively short circuit the brain and cause a seizure. These voltage-sensitive dyes allow researchers to record these rapid electrical impulses in the brain, which can be a useful tool in improving current understanding of this neurological disorder among others.
Additionally, because the dyes are dual-wavelength, they allow researchers to measure changes in voltage with greater accuracy, especially in dynamic systems like contracting hearts. Single wavelength dyes might result in distorted electrical signals due to the movement of the tissue during contraction.
The ability to focus solely on changes in voltage through a dual-wavelength ratioing technique provides a key advantage over competitors. This offers unparalleled flexibility in studying cellular electrical activity, particularly within the pharmaceutical industry.
These dyes can be used to assess the safety of potential drugs by examining their impact on cell electrical activity, says Acker. “The dyes give a readout of what the signaling is looking like if it’s being distorted or influenced by the drugs in a way that might ultimately be dangerous if it was ever taken by a patient,” he says. “It’s a way to make sure that drugs are safe as they’re being developed.”
This application is indispensable for drug safety testing and, in the future, personalized medicine, paving the way for more patient-specific treatments.
The team plans on utilizing the SBIR Phase II grant to grow the company and optimize the voltage-sensitive dyes. They are committed to making the technology as practical and user-friendly as possible to encourage more researchers and pharmaceutical companies to explore its potential.