Researchers have developed a nano-thermometer that can take the temperature of human cells, technology that could provide new insights for the treatment of cancer and other medical applications.
A team at Rice University used the light-emitting properties of particular molecules to create the fluorescent thermometer, modifying a biocompatible molecular rotor known as boron dipyrromethene—or BODIPY, for short--to reveal temperatures inside single cells.
Rice University chemists modified BODIPY molecules to serve as nano-thermometers inside cells. The chart on the left is a compilation of fluorescent lifetime micrographs showing the molecules’ response to temperature, in Celsius. At right, the structure of the molecule shows the rotor, at bottom, which is modified to restrict 360-degree rotation. (Image source: Meredith Ogle)
Angel Martí, an associate professor of chemistry, bioengineering, and materials science and nanoengineering at the university, told Design News that his team set out to develop a molecular temperature probe capable of sensing cellular temperature that needed to meet certain requirements.
“It needed to be soluble in water, non-toxic to cells, not responsive to pH, bright, and sensitive to temperature,” he said.
Researchers identified BODIPY as the material to help them achieve their aim because of certain characteristics of the molecule, Martí said. Its fluorescence lasts only a little while inside the cell, and the duration depends heavily on changes in both temperature and the viscosity of its environment. However, at high viscosity—which is the environment in typical cells--its fluorescence lifetime depends on temperature alone.
“The BODIPY probe has a phenyl group that can move, or partially rotate,” Martí explained to Design News. “The faster it moves, the faster the emission lifetime. At the temperature increases, the phenyl group moves faster and the lifetime gets smaller.”
Effective When Wobbly
Martí and Rice graduate student Meredith Ogle observed in developing the technology that the technique to measure cell temperature depends on the rotor. They constrained the rotor to go back and forth, wobbling rather than letting it rotate fully, Martí said.
“What we measure is how long the molecule stays in the excited state, which depends on how fast it wobbles,” he said in a press statement. “If you increase the temperature, it wobbles faster, and that shortens the time it stays excited.”
The effect, Martí said, is conveniently independent of the concentration of BODIPY molecules in the cell and of photobleaching, which is the point at which the molecule’s fluorescent capabilities are destroyed.
“If the environment is a bit more viscous, the molecule will rotate slower,” Martí said. “That doesn’t necessarily mean it’s colder or hotter, just that the viscosity of the environment is different.”
In this way researchers can gauge the temperature inside a cell, he said. They used a Fluorescence Lifetime Imaging microscope (FLIM) to measure the fluorescence lifetime of molecules, Martí added.
Aid for Cancer Treatment
Knowing what the temperature is inside of a cell is helpful for a number of scientific and medical observations, Martí told us.
“A variety of things are not known about cells and temperature that could be addressed with molecular thermometers,” he explained to Design News. “For example, certain medical technologies for the treatment of cancer are based on radio frequency ablation. The use of radio frequencies can cause cancer cells to heat up and die. However, how the temperature of cells change when exposed to radio frequencies is not known.”
So by using a nano-thermometer like the one the team developed, researchers could determine if heat distributes homogeneously in cells or concentrates in certain areas, or distinguish abnormalities in cells based on their temperature, Martí said. “These are just some possible applications,” he told us.
The team published a paper on its work in the Journal of Physical Chemistry B.
Researchers plan to continue their work on the nano-thermometer with the goal of encapsulating its molecule to completely decouple its ability to sense temperature from other environmental factors, such as polarity and viscosity, Martí told Design News.
Elizabeth Montalbano is a freelance writer who has written about technology and culture for more than 20 years. She has lived and worked as a professional journalist in Phoenix, San Francisco and New York City. In her free time she enjoys surfing, traveling, music, yoga and cooking. She currently resides in a village on the southwest coast of Portugal.
The Midwest's largest advanced design and manufacturing event!