Resonant acoustic band gap materials have steered a new sensing technology era. This study is presented to investigate of the one-dimensional (1D) phononic crystals (PnCs), involving periodic, as well as quasi-periodic 1D layered PnCs represented as a highly sensitive biosensor to detect and monitor the quality of milk. In this regard, the numerical findings show that the examined periodic PnCs structure outperformed the quasi-periodic structure. In particular, it provides a wider phononic band gap and greater sensitivity as well. In addition, the quasi-periodic design (especially Fibonacci sequence S4) introduces multiple resonance peaks via transmission spectra, which may lead to some conflicts during the detection process. The findings reveal that the frequency of the resonant peak can effectively change with varied milk solution concentrations and temperatures. The optimized sensor is capable of differentiating between concentrations ranging between 0 and 50 % with a 10 % step, and it can also differentiate between temperatures, which range between 5 °C and 50 °C. This makes it ideal for precise detection of other liquids and solutions. The sensor performs efficiently for all milk solution concentrations. Here, the findings demonstrated that the examined defective PnC structure exhibited the most favorable sensitivity of the value of 94.34 MHz, so it showed the highest sensitivity when varying milk concentrations. In addition, the configurated sensor provided high QF and FOM values of 3,853.645161 and 157.42, respectively. On the other hand, the sensor performs very well for all temperatures of the milk solution. As such, the S
4 quasi-periodic structure is characterized as the optimal sensor structure when varying temperatures, introducing a sensitivity of 4.78 MHz/°C, QF of 4,278.521, and FOM of 7.48 °C−1.