Subtle shifts in pH can signal drastic biological changes. Cancer cells, for instance, acidify their surroundings to metastasize more effectively. Although engineered nanoparticles can scout for such conditions nearly anywhere inside an organism, most probes lack the sensitivity to reliably indicate problematic pH levels. Researchers at the University of Texas Southwestern Medical Center have now developed a library of fluorescent nanoprobes that perform across the complete physiological pH range, from 4.0 to 7.4, with exceptional sensitivity to changes in pH as small as 0.3 units (J. Am. Chem. Soc. 2014, DOI: 10.1021/ja5053158). Led by Jinming Gao, the team conjugated block copolymers with fluorophores and fluorescent quenchers. The polymers form micelles in basic conditions, corralling the fluorescent dyes and quenchers into self-assembled, optically silent nanoparticles. But at lower pH, the micelles fall apart and the dyes are free to fluoresce. By selectively altering the hydrophobicity of certain monomer pairs within the copolymer composition, researchers fine-tuned a probe’s on/off pH. Gao says biocompatibility tests are ongoing in his lab, but preliminary studies have shown that the probes are safe for cancer imaging and tumor resectioning in mice.