We present a CMOS-compatible double gate and label-free C-reactive protein (CRP) sensor, based on silicon on insulator (SOI) silicon nanowires arrays. We exploit a reference subtracted detection method and a super-Nernstian internal amplification given by the double gate structure. We overcome the Debye screening of charged CRP proteins in solutions using antibodies fragments as capturing probes, reducing the overall thickness of the capture layer. We demonstrate the internal amplification through the pH response of the sensor, in static and realtime working modes. While operated in back-gate configuration, the sensor shows excellent stability (<20 pA/min in the worst case), low hysteresis (<300 mV), and a great sensitivity up to 1.2 nA/dec toward CRP proteins in the linear response range. The reported system is an excellent candidate for the continuous monitoring of inflammation biomarkers in serum or interstitial fluid.

In this work we report the first CMOS-compatible label-free C-Reactive Protein (CRP) differential-mode sensors and sensing method based on double-gate Si nanowires (SiNWs) FET arrays. The sensor is first validated for pH static and dynamic sensing, showing near-ideal characteristics, recommending it for the continuous monitoring of proteins in their physiological range. The system shows an excellent stability thanks to a reference subtracted operational mode, with a current sensitivity to CRP up to 1.2nA/decade on a wide concentration range between 0.6μg/ml and 100μg/ml (corresponding to typical CRP concentration ranges in blood), while operated in a pseudo-super-Nernstian back-gate configuration. The calculated limit-of-detection (LoD) is 0.73μg/ml. The sensor response is characterized by a great stability over time, showing a drift lower than 3pA/minute in the optimal bias condition, and a hysteresis lower than 300mV. The sensor offers some of the best ever reported performance tradeoffs in fully integrated sensors. The selectivity is enhanced by using specific CRP antibodies Fab fragments, reducing the overall thickness of the sensing functionalization, but preserving the binding sites. Thus, the sensor is more resilient to the Debye screening in ionic solutions, resulting in a detectable perturbation of the SiNWs array output current. The high surface-to-volume ratio of the SiNWs structures, together with a signal amplification and signal-to-noise ratio obtained with a double-gate configuration makes the reported system an excellent candidate for an integrated wearable FET-based multi-marker sensor platform, able to continuously monitor inflammation biomarkers in serum and interstitial fluid.