A Purdue physicist has created technology to detect motion inside three-dimensional tumor spheroids, which may enhance the pharmaceutical industry's early drug discovery capabilities. Physics professor David D. Nolte has developed Holographic Tissue Dynamics Spectroscopy (TDS), a technology that allows researchers to look inside cells using holography and lasers. The technology was highlighted in a letter of the peer-reviewed Journal of Biomedical Optics. The work is done in collaboration with John Turek, professor of basic medical sciences at Purdue. "This technique measures the living motion that is going on inside a cell," Nolte said. "We're picking up the actual motion, all that activity going on inside the cell, and seeing how the cells are modifying their activities in response to applied drugs." Spectrograms show how the insides of cells react to drugs, for instance when they interact with a metabolic drug (iodoacetate) relative to an antimitosis drug (cytochalasin). The Holographic TDS technology was developed by Purdue physicist David D. Nolte and can be licensed through the Purdue Research Foundation Office of Technology Commercialization. (Image: David D. Nolte) The first process used by Nolte's technology is holography, which shows a tumor tissue in three dimensions. "Most drug development takes place in a two-dimensional environment, but there are differences in how cells respond to drugs in a three-dimensional environment," Nolte said. "My colleagues and I make digital holograms of the tumor, which can grow up to one millimeter in size. With this holographic technique with lasers, we see all the way through the tumor, not just the surface." Nolte compared the holographic effects to those of a pair of polarized sunglasses. "If a car travels toward you on a sunny day, you cannot see the driver because the glare off the windshield prevents you from seeing inside. The image-bearing light of the driver is actually there; you just can't see it because your eye is being saturated with the glare," he said. "But put on a pair of polarized sunglasses to take away the glare, and you can see the driver. Our holographic approach gets rid of the light scattered by skin and tissue, and we uncover the image-bearing light that is already there." The newly developed tissue dynamics spectroscopy used in Nolte's technology creates an image similar to a voice print used in voice-recognition security software. This voice print shows changes taking place inside the cells. "After making the hologram, my colleagues and I use spectroscopy to measure the time-dependent changes in the hologram," Nolte said. "Fluctuation spectroscopy breaks down the changes into different frequencies, and we can tell how a cell's membranes, mitochondria, nucleus and even cell division respond to drugs. We measure the frequency of the light fluctuations as a function of time after a drug is applied." The resulting colorful frequency-versus-time spectrogram represents a unique voice-print of the drug used on the cells. "We've discovered that individual drugs have quite different spectrograms, but with similarities within specific classes of drugs," Nolte said. "By looking at how the cell motion is responding to drugs, we can differentiate very fine mechanistic points between them." Drug researchers and manufacturers may benefit from seeing how various drug candidates affect organ-like structures inside a cell — including the mitochondria and nucleus — by being able to more quickly determine which drug candidates are most effective in battling tumors and other tissue diseases. "There are thousands of drug candidates that may be beneficial in some way, but they need to be screened quickly and cheaply. Then drug manufacturers can spend more money to develop them," Nolte said. "This technology, with its high-throughput aspect, allows manufacturers to place a different tumor into 384 plates, test 384 different drug compounds and create 384 spectrograms in six hours." For more information, visit: www.purdueresearchpark.com