Capacitive Micromachined Ultrasonic Transducer (CMUT)-based Biosensor for Detection of Low Concentration Neuropeptide.

Accurate detection of neuropeptides in cerebrospinal fluid (CSF) plays an important role in both indepth studies and early diagnosis of neurological diseases. Here, we report a biosensor based on Capacitive Micromachined Ultrasonic Transducer (CMUT) which is capable of detecting low concentrations (pg $\sim $ ng/ml) of a neuropeptide involved with the progression of Alzheimer's diseases, somatostatin (SST). A 10-MHz CMUT was fabricated and utilized as a physical resonant sensor which detects the change in the concentration of analyte through the mass-loading mechanism. The resonant plate was sequentially coated with protein G and antibodies to provide specificity to SST; Cysteine-tagged protein G layer enables controlled immobilization of antibodies in a welloriented manner. The change in the resonant frequency of the CMUT sensor was measured after incubating the sensor in various concentrations of SST. The significant shifts in the resonant frequency were observed for SST concentrations in the range of 10 pg/ml $\sim 1$ ng/ml. Compared to the previously reported biosensors developed for SST detection, our sensor shows discernable responses for SST that are $\sim 6$ orders of magnitude lower in concentration. Thus, this work demonstrates the potential of the CMUT resonant sensor as a promising biosensor platform for detection of neuropeptides involved with neurodegenerative diseases that often exist in low concentrations in CSF.