Antibody mimic proteins (AMPs) are poly-peptides that bind to their target analytes with high affinity and specificity, just like conventional antibodies, but are much smaller in size (2-5 nm, less than 10kDa). In this report, we describe the first application of AMP in the field of nanobiosensors. In 2 O 3 nanowire based biosensors have been configured with an AMP (Fibronectin, Fn) to detect nucleocapsid (N) protein, a biomarker for severe acute respiratory syndrome (SARS). Using these devices, N protein was detected at sub-nanomolar concentration in the presence of 44 µM bovine serum albumin as a background. Furthermore, the binding constant of the AMP to Fn was determined from the concentration dependence of the response of our biosensors.

Nanowire/nanotube biosensors have stimulated significant interest; however the inevitable device-to-device variation in the biosensor performance remains a great challenge. We have developed an analytical method to calibrate nanowire biosensor responses that can suppress the device-to-device variation in sensing response significantly. The method is based on our discovery of a strong correlation between the biosensor gate dependence (dIds/dVg) and the absolute response (absolute change in current, ΔI). In2O3 nanowire based biosensors for streptavidin detection were used as the model system. Studying the liquid gate effect and ionic concentration dependence of strepavidin sensing indicates that electrostatic interaction is the dominant mechanism for sensing response. Based on this sensing mechanism and transistor physics, a linear correlation between the absolute sensor response (ΔI) and the gate dependence (dIds/dVg) is predicted and confirmed experimentally. Using this correlation, a calibration method was developed where the absolute response is divided by dIds/dVg for each device, and the calibrated responses from different devices behaved almost identically. Compared to the common normalization method (normalization of the conductance/resistance/current by the initial value), this calibration method was proved advantageous using a conventional transistor model. The method presented here substantially suppresses device-to-device variation, allowing the use of nanosensors in large arrays.

Biomarker detection based on nanowire biosensors has attracted a significant amount of research effort in recent years. However, only very limited research work has been directed toward biomarker detection directly from physiological fluids mainly because of challenges caused by the complexity of media. This limitation significantly reduces the practical impact generated by the aforementioned nanobiosensors. In this study, we demonstrate an In(2)O(3) nanowire-based biosensing system that is capable of performing rapid, label-free, electrical detection of cancer biomarkers directly from human whole blood collected by a finger prick. Passivating the nanowire surface successfully blocked the signal induced by nonspecific binding when performing active measurement in whole blood. Passivated devices showed markedly smaller signals induced by nonspecific binding of proteins and other biomaterials in serum and higher sensitivity to target biomarkers than bare devices. The detection limit of passivated sensors for biomarkers in whole blood was similar to the detection limit for the same analyte in purified buffer solutions at the same ionic strength, suggesting minimal decrease in device performance in the complex media. We then demonstrated detection of multiple cancer biomarkers with high reliability at clinically meaningful concentrations from whole blood collected by a finger prick using this sensing system.

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Nanobiosensors have drawn significant research interest in recent years owing to the advantages of label-free, electrical detection. However, nanobiosensors fabricated by bottom-up process are limited in terms of yield and device uniformity due to the challenges in assembly. Nanobiosensors fabricated by top-down process, on the other hand, exhibit better uniformity but require time and costly processes and materials to achieve the critical dimensions required for high sensitivity. In this report, we introduce a top-down nanobiosensor based on polysilicon nanoribbon. The polysilicon nanoribbon devices can be fabricated by conventional photolithography with only materials and equipments used in the standard CMOS process, thus resulting in great time and cost efficiency, as well as scalability. The devices show great response to pH changes with a wide dynamic range and high sensitivity. Biomarker detection is also demonstrated with clinically relevant sensitivity. Such results suggest that polysilicon nanoribbon devices exhibit great potential toward a highly efficient, reliable and sensitive biosensing platform.