Label-free detection of AR-V7 mRNA in prostate cancer using Yb₂Ti₂O₇ -based electrolyte-insulator-semiconductor biosensors

We developed an Yb₂Ti₂O₇-electrolyte-insulator-semiconductor (EIS) biosensor that can rapidly discriminate clinical statuses of prostate cancer (PCa) by detecting the existence of androgen-receptor splice variant 7 (AR-V7) messenger RNA. The structural feature of YbTi_xO_y sensing membranes anneal to Si substrates through reactive cosputtering with different annealing temperatures investigated. Results showed annealed at 900°C exhibited higher sensitivity of 61.11 mV/pH, lower hysteresis voltage of 1.6 mV, and smaller drift rate of 0.16 mV/hr. This attributed to the well-crystallized Yb₂Ti₂O₇ structure, detected using X-ray diffraction and X-ray photoelectron spectroscopy. We then compared two different methods, encapsulating or covalently bonding of the probe, to detect existence of AR-V7 in PCa. After hybridization of the probe with the target cDNA sequence, the covalent binding of AR-V7 probe method exhibited a larger V_REF shift in the capacitance-voltage curves for the detection of AR-V7. Furthermore, highly reliable and stable results (>95% repetition rate) also could be observed when compared to that encapsulated probe on the EIS. Our data demonstrated this AR-V7 probe-based Yb₂Ti₂O₇-EIS biosensor is a rapid, simple, label-free, economical, and accurate diagnostic device, and provide fast identification of resistant statuses in circulating tumor cells of PCa, essential for clinicians to make defining decisions.