Tiny Temperature Sensors

Luis Carlos first realized he might be able to make a nanothermometer while developing light-emitting diodes more than 15 years ago. His team observed that lanthanide ions in the diodes reacted to changes in temperature by reliably shifting the color they emitted. Carlos, a nanomaterials scientist based at the University of Aveiro, immediately realized that these ions might have a destiny beyond simply supplying the color for LED lights or displays. So he and his colleagues submitted a paper demonstrating that lanthanide ions could be used as temperature sensors. But its publication was initially turned down. What’s the point of using light emission to detect temperature, one reviewer asked, when easier and more robust techniques, like thermocouples or infrared imaging, are already commercially available? “Of course this is true”, Carlos says, “but [the reviewer] wasn’t thinking on the nanoscale”a size regime at which established thermometric techniques are too bulky and lack the sensitivity to work. It also wasn’t clear what the value of temperature sensing on such a small scale could be, he adds. Initially, Carlos developed lanthanide nanoscale thermometers to measure temperature gradients in electronic materials, but collaborators soon guided him toward another application: thermometric probes that could monitor tumor cells. At the time, scientists had begun testing an experimental cancer therapy that would kill tumor cells by heating them to above 40 °C. However, too much heat damages surrounding tissues, so the ability to monitor temperature change in targeted cells is key. Carlos isn’t alone in applying tiny temperature-sensing particles to biological systems. Nanoparticles are the right size and have properties that make them ideal for measuring the temperature of cells and even of the organelles within them. Conditions such as inflammation and diseases such as cancer are accompanied by hyperlocal temperature changes in tissues, so nanothermometers could have broad applications for both health monitoring and treatment. The tools are also poised to address basic questions about cell biology. Chemical reactions within a cell produce heat, but researchers know little about how such heat affects processes in the cell, or the organism in which it resides. An increase in temperature may serve as a cue to switch other reactionsor the transcription of certain geneson or off. “Our hypothesis is that the living organism may use this ultra-locally-produced heat as another type of intracellular signaling”, says Madoka Suzuki, a biophysicist at Japan Science & Technology Agency. “But nobody knows, because there has been no method” to detect it, he adds. Scientists have known since the 1970s that temperature affects the light emission of certain chemical species, but not until the turn of the 21st century did they begin to harness this property for nanoscale sensing. A seminal article laying out the concept of using luminescent nanoparticles for thermometry was published in 2002 by researchers at Nomadics, Inc., an Oklahoma-based company that makes chemical and other sensors. It took another few years for efforts to blossom. Since about 2010, multiple groups have developed nanoscale thermometers that can detect temperature changes with a sensitivity of less than 1 °C. “The signal of the luminescence and the thermal resolution