Biomarker detection based on nanoparticle-induced ultrasonic Rayleigh scattering

Ultrasonic biochemical detection is important for biomarker detection, drug monitoring, and medical diagnosis, as it can predict disease progression and enable effective measures to be taken in a timely manner. However, the ultrasonic technology currently used for biochemical marker detection is directly modified on the surface of the device. The associated test methods are costly and unreliable while having poor repeatability; therefore, they cannot achieve low-cost rapid testing. In this study, a detection mechanism based on the Rayleigh scattering of acoustic waves caused by nanoparticles, which causes changes in the received sound pressure, was developed for the first time. The modification of antibodies on an insertable substrate decouples the functionalization step from the sensor surface and facilitates the application of capacitive micromachined ultrasonic transducers (CMUTs) in conjunction with Au nanoparticles (AuNPs) for CA19-9 cancer antigen detection. A corresponding detection theory was established, and the relevant parameters of the theoretical formula were verified using different nanoparticles. Using our fabricated CMUT chip with a resonant frequency of 1 MHz, the concentrations and substances of the CA19-9 antigen markers were successfully measured. In the concentration range of 0.1-1000 U/mL, the receiving voltage decreased with increasing concentration. Further investigations revealed that the influence of other interfering markers in the human body can be ignored, demonstrating the feasibility and robustness of biochemical detection based on CMUTs combined with nanoparticles.