Marco Curreli

Real-Time, Label-Free Detection of Biological Entities Using Nanowire-Based FETs

Nanowire (NW)-based FETs are promising devices with potential applications ranging from health monitoring to drug discovery. In fact, these devices have demonstrated the ability to detect a variety of analytes such as particular DNA sequences, cancer biomarkers, and larger entities such as viruses. These sensor devices have also been used to monitor enzymatic activities and study the behavior of potential drug molecules. The detection of the analytes occurs with high specificity and sensitivity in reasonably short time. Here, we review the recent literature produced in the field of NW FET biosensors. We elaborate on the parameters that ultimately influence device performance such as methods of NW production, device dimensionality, and active measurement conditions. Significant progress has been made in this field of technology; however, it is often difficult to compare literature reports due to differences in both measurement conditions and data analysis. The standardization of certain active measurement conditions, such as the ionic strength of the analyte solutions, and manipulation of data are proposed to facilitate comparison between different NW biosensors.

Label-free, electrical detection of the SARS virus N-protein with nanowire biosensors utilizing antibody mimics as capture probes.

Antibody mimic proteins (AMPs) are polypeptides 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 10 kDa). 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 subnanomolar concentration in the presence of 44 microM 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.

A Calibration Method for Nanowire Biosensors to Suppress Device-to-Device Variation

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 (dI(ds)/dV(g)) and the absolute response (absolute change in current, DeltaI). In(2)O(3) 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 (DeltaI) and the gate dependence (dI(ds)/dV(g)) is predicted and confirmed experimentally. Using this correlation, a calibration method was developed where the absolute response is divided by dI(ds)/dV(g) 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 proven advantageous using a conventional transistor model. The method presented here substantially suppresses device-to-device variation, allowing the use of nanosensors in large arrays.

Importance of Controlling Nanotube Density for Highly Sensitive and Reliable Biosensors Functional in Physiological Conditions

Biosensors utilizing carbon nanotube field-effect transistors have a tremendous potential to serve as the basis for the next generation of diagnostic systems. While nanotubes have been employed in the fabrication of multiple sensors, little attention has previously been paid to how the nanotube density affects the biosensor performance. We conducted a systematic study of the effect of density on the performance of nanotube biosensors and discovered that this parameter is crucial to achieving consistently high performance. We found that devices with lower density offer higher sensitivity in terms of both detection limit and magnitude of response. The low density nanotube devices resulted in a detection limit of 1 pM in an electrolyte buffer containing high levels of electrolytes (ionic concentration ∼140 mM, matching the ionic strength of serum and plasma). Further investigation suggested that the enhanced sensitivity arises from the semiconductor-like behavior-strong gate dependence and lower capacitance-of the nanotube network at low density. Finally, we used the density-optimized nanotube biosensors to detect the nucleocapsid (N) protein of the SARS virus and demonstrated improved detection limits under physiological conditions. Our results show that it is critical to carefully tune the nanotube density in order to fabricate sensitive and reliable devices.

Selective, electrochemically activated biofunctionalization of In2O3 nanowires using an air-stable surface modifier.

Selective electrochemically activated biofunctionalization of In(2)O(3) nanowires (NWs) has been achieved, using monolayer coatings of p-dimethoxybenzene derivatives. Monolayer coatings of 4-(2,5-dimethoxyphenyl)butyl-phosphonic acid (DMP-PA) were deposited on planar indium-tin oxide (ITO) electrodes and In(2)O(3) NWs. The electrochemical behavior of the monolayer coating was first studied using ITO electrodes, as a model system for In(2)O(3) nanowires. When a potential of 950 mV vs a Ag/AgCl reference electrode is applied to an ITO electrode coated with DMP-PA in PBS buffer, the p-dimethoxyphenyl groups are converted to p-benzoquinone (BQ). The electrochemically formed benzoquinone groups react readily with alkyl thiol groups via a Michael addition. The reaction strategy optimized on ITO was applied to an In(2)O(3) NW mat sample coated with DMP-PA. Applying a potential of 950 mV to metal electrodes deposited on NWs converts the DMP-PA NW coating to BQ-PA, which reacts with a thiol-terminated 20-base oligonucleotide. These NWs showed strong fluorescence response after paring with the dye labeled compliment, demonstrating that the probe was bound to the NW surface and that it remained active toward hybridization with its compliment. The unactivated DMP-PA coated NWs showed no response, demonstrating the selective electrochemical functionalization of NWs and the potential of using them in multiplex sensing. We also compared the p-dimethoxybenzene derivative to the conventional hydroquinone analog. The results show that the former can largely enhance the selectivity during the functionalization of both ITO and In(2)O(3) NWs.

Emergence of nanomedical devices for the diagnosis and treatment of cancer: the journey from basic science to commercialisation

Nanobiosensors and Near-Infrared Light Absorbing Nanomaterials (NIRLANs) may revolutionise the diagnosis and therapy of cancer. This paper briefly explains how nanomedical devices work and then analyses the issues involved in translating such concept devices into valuable commercial products. While oncology nanodevices have already demonstrated enormous potential in anti-cancer therapy, the benefits of these innovative medical products cannot be fully realised without safety and clinical efficacy testing, compliance with regulations, and adequate protection of intellectual property for commercialisation. While medical nanotechnology holds great promise for the diagnosis and treatment of cancers, the path to successful commercialisation poses numerous new challenges.

Studies on Biosensing Property and Functionalization of In2O3 and Carbon Nanotube Field Effect Transistor

Biosensing property and functionalization of In2O3 nanowire and carbon nanotube field effect transistor were investigated. Low-density lipoproteins adsorbed on their surface were found to give complementary effects on their electrical property, e.g., enhanced conductance in NW and suppressed conductance in CNT. Prostate specific antigen was selectively detected by functionalizing the sensors with PSA antibody via linker molecules. It was found that the exposure to 0.14 nM (5 ng/ml) PSA increases the conductance of In2O3 nanowire by 1.3 %, while 1.4 nM (50 ng/ml) PSA decreases that of carbon nanotube by 2 %. Additionally, selective functionalization of Indium Tin Oxide thin film and In2O3 NWs with probe DNA single strand was achieved by selectively converting hydroquinone into quinone using electrochemistry, as confirmed by the fluorescence study.

Nanosensing applications of In2O3 nanowires and carbon nanotubes

We report complementary detection of prostate-specific antigen (PSA) using n-type In2O3 nanowires and p-type carbon nanotubes. Our innovation involves developing an approach to covalently attach antibodies to In2O3 NW surfaces via the onsite surface synthesis of phosphoric acid-succinylimide ester. Electronic measurements under dry conditions revealed complementary response for In2O3 NW and SWNT devices after the binding of PSA. Real time detection in solution has also been demonstrated for PSA down to 5 ng/mL, a benchmark concentration significant for clinical diagnosis of prostate cancer, which is the most frequently diagnosed cancer.