Rapid, label-free, electrical whole blood bioassay based on nanobiosensor systems.

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.

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.

A nanoelectronic enzyme-linked immunosorbent assay for detection of proteins in physiological solutions.

Semiconducting nanowires are promising ultrasensitive, label-free sensors for small molecules, DNA, proteins, and cellular function. Nanowire field-effect transistors (FETs) function by sensing the charge of a bound molecule. However, solutions of physiological ionic strength compromise the detection of specific binding events due to ionic (Debye) screening. A general solution to this limitation with the development of a hybrid nanoelectronic enzyme-linked immunosorbent assay (ne-ELISA) that combines the power of enzymatic conversion of a bound substrate with electronic detection is demonstrated. This novel configuration produces a local enzyme-mediated pH change proportional to the bound ligand concentration. It is shown that nanowire FETs configured as pH sensors can be used for the quantitative detection of interleukin-2 in physiologically buffered solution at concentrations as low as 1.6 pg mL(-1). By successfully bypassing the Debye screening inherent in physiological fluids, the ne-ELISA promises wide applicability for ligand detection in a range of relevant solutions.

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.

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 nanoelectronic nose: a hybrid nanowire/carbon nanotube sensor array with integrated micromachined hotplates for sensitive gas discrimination.

A novel hybrid chemical sensor array composed of individual In(2)O(3) nanowires, SnO(2) nanowires, ZnO nanowires, and single-walled carbon nanotubes with integrated micromachined hotplates for sensitive gas discrimination was demonstrated. Key features of our approach include the integration of nanowire and carbon nanotube sensors, precise control of the sensor temperature using the micromachined hotplates, and the use of principal component analysis for pattern recognition. This sensor array was exposed to important industrial gases such as hydrogen, ethanol and nitrogen dioxide at different concentrations and sensing temperatures, and an excellent selectivity was obtained to build up an interesting 'smell-print' library of these gases. Principal component analysis of the sensing results showed great discrimination of those three tested chemicals, and in-depth analysis revealed clear improvement of selectivity by the integration of carbon nanotube sensors. This nanoelectronic nose approach has great potential for detecting and discriminating between a wide variety of gases, including explosive ones and nerve agents.

Rapid and label-free cell detection by metal-cluster-decorated carbon nanotube biosensors.

In this paper, the use of carbon nanotube biosensors toward alga cell detection was examined. The biosensor devices were fabricated on complete 4 in. wafers by first growing carbon nanotubes (CNTs) and then depositing metal electrodes using a shadow mask. In addition, we decorated the biosensors with metal-clusters resulted in enhancing the sensitivity by 2000-folds and has enabled the detection of streptavidin down to 10 pM concentration. This sensitivity enhancement was attributed to activation of CNT channels due to formation of Schottky junctions between CNTs and metal-clusters. Real-time cell detection has been successfully carried out using the CNT biosensors for two kinds of alga related to brown tides: Aureococcus anophagefferens and BT3. Functionalization of the CNT biosensors with the monoclonal antibody for A. anophagefferens has led to detection at a concentration of 10(4) cells/ml, with sensitivity lower than 10(4) cells/ml projected based on the signal-to-noise ratio of the sensors. Further functionalization with tween 20 led to suppression of non-specific binding of BT3 and enabled label-free and selective detection of A. anophagefferens. These nanobiosensors may find potential applications for environmental monitoring and disease diagnosis.

Transparent electronics based on transfer printed aligned carbon nanotubes on rigid and flexible substrates.

We report high-performance fully transparent thin-film transistors (TTFTs) on both rigid and flexible substrates with transfer printed aligned nanotubes as the active channel and indium-tin oxide as the source, drain, and gate electrodes. Such transistors have been fabricated through low-temperature processing, which allowed device fabrication even on flexible substrates. Transparent transistors with high effective mobilities (approximately 1300 cm(2) V(-1) s(-1)) were first demonstrated on glass substrates via engineering of the source and drain contacts, and high on/off ratio (3 x 10(4)) was achieved using electrical breakdown. In addition, flexible TTFTs with good transparency were also fabricated and successfully operated under bending up to 120 degrees . All of the devices showed good transparency (approximately 80% on average). The transparent transistors were further utilized to construct a fully transparent and flexible logic inverter on a plastic substrate and also used to control commercial GaN light-emitting diodes (LEDs) with light intensity modulation of 10(3). Our results suggest that aligned nanotubes have great potential to work as building blocks for future transparent electronics.

Transparent active matrix organic light-emitting diode displays driven by nanowire transistor circuitry.

Optically transparent, mechanically flexible displays are attractive for next-generation visual technologies and portable electronics. In principle, organic light-emitting diodes (OLEDs) satisfy key requirements for this application-transparency, lightweight, flexibility, and low-temperature fabrication. However, to realize transparent, flexible active-matrix OLED (AMOLED) displays requires suitable thin-film transistor (TFT) drive electronics. Nanowire transistors (NWTs) are ideal candidates for this role due to their outstanding electrical characteristics, potential for compact size, fast switching, low-temperature fabrication, and transparency. Here we report the first demonstration of AMOLED displays driven exclusively by NW electronics and show that such displays can be optically transparent. The displays use pixel dimensions suitable for hand-held applications, exhibit 300 cd/m2 brightness, and are fabricated at temperatures suitable for integration on plastic substrates.

Fabrication of fully transparent nanowire transistors for transparent and flexible electronics.

The development of optically transparent and mechanically flexible electronic circuitry is an essential step in the effort to develop next-generation display technologies, including 'see-through' and conformable products. Nanowire transistors (NWTs) are of particular interest for future display devices because of their high carrier mobilities compared with bulk or thin-film transistors made from the same materials, the prospect of processing at low temperatures compatible with plastic substrates, as well as their optical transparency and inherent mechanical flexibility. Here we report fully transparent In(2)O(3) and ZnO NWTs fabricated on both glass and flexible plastic substrates, exhibiting high-performance n-type transistor characteristics with approximately 82% optical transparency. These NWTs should be attractive as pixel-switching and driving transistors in active-matrix organic light-emitting diode (AMOLED) displays. The transparency of the entire pixel area should significantly enhance aperture ratio efficiency in active-matrix arrays and thus substantially decrease power consumption.

N-fused pentaphyrins and their rhodium complexes: oxidation-induced rhodium rearrangement.

meso-Aryl-substituted pentaphyrins were isolated in the modified Rothemund-Lindsey porphyrin synthesis as a 22-pi-electron N-fused pentaphyrin ([22]NFP5) and a 24-pi-electron N-fused pentaphyrin ([24]NFP5), which were reversibly interconvertible by means of two-electron reduction with NaBH4 or two-electron oxidation with dichlorodicyanobenzoquinone (DDQ). Judging from 1H NMR data, [22]NFP5 is aromatic and possesses a diatropic ring current, while [24]NFP5 exhibits partial anti-aromatic character. Metalation of [22]NFP5 1 with a rhodium(I) salt led to isolation of rhodium complexes 9 and 10, whose structures were unambiguously characterized by X-ray diffraction analyses and were assigned as conjugated 24-pi and 22-pi electronic systems, respectively. In the rhodium(I) metalation of 1, the complex 9 was a major product at 20 degrees C, but the complex 10 became preferential at 55 degrees C. Upon treatment with DDQ, compound 9 was converted to 10 with an unprecedented rearrangement of the rhodium atom.