Calcium Sensor for Photoacoustic Imaging

We introduce a selective and cell-permeable calcium sensor for photo­acoustics (CaSPA), a versatile imaging technique that allows for fast volumetric mapping of photo­absorbing molecules with deep tissue penetration. To optimize for Ca²⁺-dependent photo­acoustic signal changes, we synthesized a selective metallo­chromic sensor with high extinction coefficient, low quantum yield, and high photo­bleaching resistance. Micromolar concentrations of Ca²⁺ lead to a robust blue­shift of the absorbance of CaSPA, which translated into an accompanying decrease of the peak photo­acoustic signal. The acetoxy­methyl esterified sensor variant was readily taken up by cells without toxic effects and thus allowed us for the first time to perform live imaging of Ca²⁺ fluxes in genetically unmodified cells and heart organoids as well as in zebrafish larval brain via combined fluorescence and photo­acoustic imaging