Ultra-High Sensitivity Silicon Nanowire Array Biosensor Based on a Constant-Current Method for Continuous Real-Time pH and Protein Monitoring in Interstitial Fluid

In this paper we demonstrate ultra-high sensitivity silicon nanowires pH and protein sensing on the same Silicon nanowire array platform by using a constant current method and monitoring the drain voltage as function of analyte concentration. The injected current levels allow choosing the most appropriate electrical sensing conditions, which in our sensors corresponds to the moderate inversion region, providing the best tradeoff between sensitivity, stability, and power consumption. This method appears to be the most appropriate for real-time continuous measurements of biomarkers in human biofluids. Using real human sera samples, to mimic the composition of interstitial fluids (ISF), we demonstrate pH sensing in the physiopathological range from 6.5 to 8. An excellent accuracy in this complex matrix, with a maximal error as low as 0.92% (0.07 pH unit), was achieved in constant-current method at optimal current levels (1.71% for top-gate). By using different pools of human sera, with different total protein content, we show that patient to patient protein content does not influence the sensors' performance to pH. On the same sensing platform we develop and demonstrate a proof of concept for protein sensing that benefits from the signal amplification and improved SNR obtained with the proposed method by showing C-Reactive protein detection (CRP) in PBS 0.1X. The reported results aim to establish the foundations for the development of a wearable and continuous biosensor that can jointly detect pH and CRP in human interstitial fluids using silicon nanowires.