In this paper, we introduce a comprehensive theoretical study to obtain an optimal highly sensitive fluidic sensor based on the one-dimensional phononic crystal (PnC). The mainstay of this study strongly depends on the high impedance mismatching due to the irregularity of the considered quasi-periodic structure, which in turn can provide better performance compared to the periodic PnC designs. In this regard, we performed the detection and monitoring of the different concentrations of lead nitrate (Pb(NO3)2) and identified it as being a dangerous aqueous solution. Here, a defect layer was introduced through the designed structure to be filled with the Pb(NO3)2 solution. Therefore, a resonant mode was formed within the transmittance spectrum of the considered structure, which in turn shifted due to the changes in the concentration of the detected analyte. The numerical findings demonstrate the role of the different sequences such as Fibonacci, Octonacci, Thue–Morse, and double period on the performance of the designed PhC detector. Meanwhile, the findings of this study show that the double-period quasi-periodic sequence provides the best performance with a sensitivity of 502.6 Hz/ppm, a damping rate of , a maximum quality factor of 8463.5, and a detection limit of 2.45.