Presented here is a novel method of in vivo pH sensing utilizing a hybrid optical imaging technique, photoacoustic imaging (PAI), and pH sensitive polymeric nanoprobes. Nanoprobes with hydrophobic core containing a pH sensitive dye were synthesized and used to measure the pH level ex vivo first and then in vivo by performing experiments on a rat joint model, with an achieved precision of less than 0.1 pH units. The ability of the hydrophobic functional groups in the polyacrylamide matrix to shield the molecular dye from being affected by the proteins in the plasma, and prevent the dye from leaching out, is also demonstrated.
