Custom electronics tailored for ultrasonic applications with four ultrasonic transmit-receive channels and a nominal 25 MHz single channel frequency were developed for ultrasound BAW and SAW biosensor uses. The designed integrated microcontroller, supported by Python with a SciPy library, and the developed system measured the time of flight (TOF) and other wave properties to characterize the acoustic properties of a bulk of the liquid in a microchannel or acoustic properties of biological species attached to an analytic surface in real time. The system can utilize both piezoelectric and capacitive micromachined ultrasound transducers. The device demonstrated a linear response to changes in water salinity. This response was primarily attributed to the time-of-flight (TOF) changes related to the varying solution density. Furthermore, real-time DNA oligonucleotide-based interactions between oligonucleotides immobilized on the device’s analytical area and oligonucleotides attached to gold nanoparticles (Au NPs) in the solution were demonstrated. The biological interaction led to an exponential decrease in the acoustic interfacial wave propagating across the interface between the solution and the solid surface of the sensor, the TOF signal. This decrease was attributed to the increase in the effective density of the solution in the vicinity of the sensor’s analytical area, as Au NPs modified by oligonucleotides were binding to the analytical area. The utilization of Au NPs in oligonucleotide surface binding yields a considerably stronger sensor signal than previously observed in earlier CMUT-based TOF biosensor prototypes.