High sensitivity and rapid detection of KRAS and BRAF gene mutations in colorectal cancer using YbTixOy electrolyte-insulator-semiconductor biosensors

Abstract

The KRAS and BRAF genes are attractive for a predictive biomarker to determine whether the colorectal cancer (CRC) patient predicts response to anti-epidermal growth factor receptor treatment. The detection of KRAS and BRAF mutation statuses has to be considered as a diagnostic and prognostic factor for the treatment of metastatic CRC patients because the targeted therapy may be expensive as well as toxic. In this work, we develop an YbTixOy electrolyte-insulator-semiconductor (EIS) biosensor to detect the KRAS and BRAF gene mutations in CRC. X-ray diffraction, atomic force microscopy, X-ray photoelectron spectroscopy, and secondary ion mass spectrometry were used to explore the structural features of YbTixOy films prepared under three Ti plasma power conditions. We found that the YbTixOy-based EIS sensor fabricated at the 80 W condition exhibited a higher sensitivity of 69.54 mV/pH (in pH range 2–12), a lower hysteresis voltage of 1 mV (in pH loop of 7→4→7→10→7), and a smaller drift rate of 0.15 mV/h (in pH 7) than those of the other Ti plasma power conditions. Furthermore, we successfully demonstrated that the single strain DNA probe-immobilized YbTixOy EIS biosensors functionalized with 3-aminopropyl triethoxysilane followed by glutaraldehyde were screened for the KRAS and BRAF gene mutations in CRC. High sensitivity and rapid detection of the YbTixOy-based EIS biosensor are expected to serve as the diagnostic tool for clinical examination and screening with CRC.