Exchange-Paint image showing microtubules in green, mitochondria in purple, Golgi apparatus in red, and peroxisomes in yellow, from a single human cell. (Maier Avendano, Wyss Institute, Harvard University)
13 October 2015. A new enterprise based on research at Harvard University is offering a technology that allows ordinary microscopes to display high resolution images of single molecules. The company, Ultivue Inc., is founded by and licensing technologies from the lab of Peng Yin at Harvard’s Wyss Institute for Biologically Inspired Engineering.
Yin and colleagues study the behavior of organisms from the perspective of engineers or systems analysts, in this case visualizing individual molecules of DNA that carries an individual’s genetic code, or tracking activities of molecules at work in human cells. These capabilities can accelerate the development of digital pathology, making possible faster and less expensive medical diagnostics.
With current technologies, however, instruments and devices for this level of imaging are complex and expensive, requiring specialized dyes activated with lasers. Standard fluorescent microscopes by themselves cannot distinguish objects closer than 200 nanometers — 1 nanometer equals 1 billionth of a meter — that appear in images as blurry spots.
Yin’s group found a way of overcoming these barriers by developing chemical compounds that tag pieces of DNA with fluorescent dyes, which when engineered to attach to target molecules cause the target molecules to blink. This development, known as DNA-Paint, measures the blinking activity, allowing researchers to calibrate their instruments to yield clear images with resolutions under 10 nanometers.
The research team later extended DNA-Paint to develop a technology for capturing images of multiple molecules at once. This technology called Exchange-Paint harnesses the behavior of DNA strands to link up with other DNA strands having complementary sequences of nucleic acids reflecting one’s genetic code. With Exchange-Paint, the strands light up the fluorescent dye when the two complementary strands connect, then stop illuminating when they disengage. Yin and colleagues developed techniques for programming the speed of connections, and thus blinking rate of the connected strands, as well as assigning colors to code the type of molecule being visualized.
“We can now study many processes at a molecular level such as changes in chromosomes or minuscule neuronal structures,” says Yin in a Wyss Institute statement. “We also could determine molecular states of diseases in a more comprehensive fashion and with much greater detail, providing an enabling platform for digital pathology.”
Ultivue has a worldwide license from Harvard University to commercialize DNA-Paint and Exchange-Paint, with the goal of developing an inexpensive microscopic platform for images at the molecular level. Yin already recruited key members of the lab’s research team as co-founders and staff scientists.
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