Two dimensional fluorescent MOF sensor, TMU-5S, was synthesized by introducing Rhodamine B into the framework of TMU-5. This dye sensitized MOF was explored as a ratiometric fluorescent sensor for Ca2+ signaling in presence of interfering cations in ionic concentrations similar to that of blood plasma that exhibits exceptional sensitivity and selectivity to Ca2+ and faster response and recovery times than any other reported fluorescent sensor. This can be attributed to strong electrostatic interactions between basic azine groups in the narrow pore walls of TMU-5S and Ca2+ as hard-hard acid-base interactions. The results show that the two dimensional signal transduction can reduce interfering responses from the environment and thus create exceptional sensitivity.