Scientists at the Okinawa Institute of Science and Technology (OIST) Graduate University have developed a light-based device that can act as a biosensor, detecting biological substances in materials, such as harmful pathogens in food. The scientists said that their tool, an optical microresonator, is 280× more sensitive than current industry-standard biosensors, which can detect only cumulative effects of groups of particles, not individual molecules. Microresonators are central to a new method for single-particle photothermal absorption spectroscopy, whereby the microresonators act as microscale thermometers to detect the heat dissipated by optically pumped, nanoscopic targets. However, translation of this technology to chemically dynamic systems requires a platform that is mechanically stable, solution-compatible, and visibly transparent. For this research, microbubble absorption spectrometers served as the platform for meeting these requirements. The microbubbles integrated a two-port microfluidic device within a whispering gallery mode microresonator, allowing for the exchange of chemical reagents within the resonator’s interior, while maintaining a solution-free exterior environment. Photothermal maps of a microbubble resonator, both out-of-focus (top left), and in-focus (bottom left). Optical micrographs of two microbubble resonators with different geometries (right). Scale bars: 20 µm. Courtesy of ACS Nano. The OIST researchers, in collaboration with scientists from the University of Wisconsin, coated the inside of a microbubble resonator with gold nanorods. They shined a laser beam on the nanorods to heat them, then observed how the shape, orientation, and surface chemistry of the nanorods changed when they were exposed to certain chemicals and light fields. The photoactivated etching of single gold nanorods provided the researchers with a way to rapidly acquire spatial and morphological information about the nanoparticles as they underwent chemical reactions. Temperature increases in the nanorods caused shifts in the light frequencies emitted by the resonator. The scientists were then able to measure and image these shifts in nanoparticle temperature at very high resolution. Next, the scientists plan to apply this photothermal sensing technique to proteins. They will coat the inside of the resonator with proteins instead of gold nanorods, then observe whether changes in protein shape change the optical and thermal properties of the proteins. The researchers believe their method could also be useful for detecting tiny viruses or single DNA strands. “Normally, if you want to get high-resolution images of tiny proteins, you would need an electron microscope, which would damage the protein,” researcher Jonathan Ward said. “The potential here for commercialization is huge, although there are still many technical challenges to overcome.” The research was published in ACS Nano (www.doi.org/10.1021/acsnano.9b04702).