Detection of the melanoma biomarker TROY using silicon nanowire field-effect transistors

Antibody-functionalized silicon nanowire field-effect transistors have been shown to exhibit excellent analyte detection sensitivity enabling sensing of analyte concentrations at levels not readily accessible by other methods. One example where accurate measurement of small concentrations is necessary is detection of serum biomarkers, such as the recently discovered tumor necrosis factor receptor superfamily member TROY (TNFRSF19), which may serve as a biomarker for melanoma. TROY is normally only present in brain but it is aberrantly expressed in primary and metastatic melanoma cells and shed into the surrounding environment. In this study, we show the detection of different concentrations of TROY in buffer solution using top-down fabricated silicon nanowires. We demonstrate the selectivity of our sensors by comparing the signal with that obtained from bovine serum albumin in buffer solution. Both the signal size and the reaction kinetics serve to distinguish the two signals. Using a fast-mixing two-compartment reaction model, we are able to extract the association and dissociation rate constants for the reaction of TROY with the antibody immobilized on the sensor surface

Sensing of the melanoma biomarker TROY using silicon nanowire field-effect transistors

Antibody-functionalized silicon nanowire field-effect transistors have been shown to exhibit excellent analyte detection sensitivity enabling sensing of analyte concentrations at levels not readily accessible by other methods. One example where accurate measurement of small concentrations is necessary is detection of serum biomarkers, such as the recently discovered tumor necrosis factor receptor superfamily member TROY (TNFRSF19), which may serve as a biomarker for melanoma. TROY is normally only present in brain but it is aberrantly expressed in primary and metastatic melanoma cells and shed into the surrounding environment. In this study, we show the detection of different concentrations of TROY in buffer solution using top-down fabricated silicon nanowires. We demonstrate the selectivity of our sensors by comparing the signal with that obtained from bovine serum albumin in buffer solution. Both the signal size and the reaction kinetics serve to distinguish the two signals. Using a fast-mixing two-compartment reaction model we are able to extract the association and dissociation rate constants for the reaction of TROY with the antibody immobilized on the sensor surface.The authors thank Biosite Diagnostics (San Diego, CA) for providing TROY antibodies. The authors acknowledge NIH, NSF, and Battelle Memorial Institute for support of this work. (NIH; NSF; Battelle Memorial Institute)https://pubs.acs.org/doi/pdf/10.1021/acssensors.6b00017Accepted manuscrip

Towards The Development of Biosensors for the Detection of Microbiologically Influenced Corrosion (MIC)

Corrosion is one of the biggest concerns for mechanical integrity of infrastructure and infrastructural components, such as oil refineries, bridges and roads. The economic cost of corrosion is typically estimated to be between 1 to 5 % of the gross national product (GNP) of countries, of which the contribution of microbiologically influenced corrosion (MIC) is estimated to be between 10% and 50%. Current state-of-the-art approaches for detecting MIC primarily rely on ex-situ tests, including bacterial test kits (bug bottles); corrosion coupons, pigging deposits analysis and destructive analysis of MIC affected sites using SEM, TEM, and XRD. These ex-situ measurements do not capture the complexities and time sensitivities underlying MIC. This is owed to the fact that the proliferation of the microbial contamination is a dynamic and rapid process, and any delay can prove expensive as it is estimated that once the biofilm formation takes place the amount of biocides needed is magnitude of orders more as compared to when the bacteria are in planktonic form. Additionally, the field environment is a complex biotic and abiotic environment which is often difficult to replicate even in high fidelity laboratory models. Hence a real-time/pseudo real-time method of detection would greatly help reduce the costs and optimize biocide-based mitigation of MIC. To overcome the above-mentioned shortcomings associated with the state-of-the-art; this work is aimed at the development of a sensor substrate whereby highly specific detection can be carried out in the environment where the corrosion exists, in a real-time/pseudo real-time basis. More specifically, the research is aimed at the development of sensors based on a nanowire matrix functionalized with biomolecules which can perform this specific and real-time detection of MIC in the pipeline environment. Here, the detection of MIC is based on the binding of specific biomolecules causing MIC to organic molecules anchored on top of the nanowires. These sensors also need to be inexpensive (made of low-cost, earth abundant materials), have low power consumption, and robustly deployable. The primary component of the detection platforms are copper oxide nanowire arrays (CuONWs with lengths of 25 to 30 m, 50 to 100 nm in diameter) and silicon nanowires arrays (SiNWs with lengths of 5 to 8 m, 45 to 100 nm in diameter). They are synthesized using facile and scalable techniques and are selected for their robust electrical and mechanical properties. Electrochemical degradation studies of the NWs were performed in 3.5 wt. % NaCl solution and simulated produced water using polarization and electrochemical impedance spectroscopy (EIS). The NWs systems showed robust resistance to degradation despite higher surface area (as compared to bulk counterparts), and both diffusion limitations and charge transfer resistance was observed on the analysis of the impedance response. The ability to immobilize a variety of moieties on the nanowire platforms gives them the ability to detecting a wide variety of MIC biomarkers. The Biotin-Streptavidin (SA) complex was used as a proof of concept to test the viability of the NW arrays as a substrate for sensing. A custom test bed was built for the functionalized NW thin films, and cyclic voltammetry studies revealed a stable current response with time for 10nM and 10,000 nM SA concentrations. The use of different probes such as aptamers to larger immunoglobulin probes provides the flexibility to detect the full spectrum of biomarkers. The development of these next generation sensor platforms along with the methodologies employed to stabilize them and assemble them into functional devices are explored in detail in this dissertation

Applications of Graphene Quantum Dots in Biomedical Sensors

Due to the proliferative cancer rates, cardiovascular diseases, neurodegenerative disorders, autoimmune diseases and a plethora of infections across the globe, it is essential to introduce strategies that can rapidly and specifically detect the ultralow concentrations of relevant biomarkers, pathogens, toxins and pharmaceuticals in biological matrices. Considering these pathophysiologies, various research works have become necessary to fabricate biosensors for their early diagnosis and treatment, using nanomaterials like quantum dots (QDs). These nanomaterials effectively ameliorate the sensor performance with respect to their reproducibility, selectivity as well as sensitivity. In particular, graphene quantum dots (GQDs), which are ideally graphene fragments of nanometer size, constitute discrete features such as acting as attractive fluorophores and excellent electro-catalysts owing to their photo-stability, water-solubility, biocompatibility, non-toxicity and lucrativeness that make them favorable candidates for a wide range of novel biomedical applications. Herein, we reviewed about 300 biomedical studies reported over the last five years which entail the state of art as well as some pioneering ideas with respect to the prominent role of GQDs, especially in the development of optical, electrochemical and photoelectrochemical biosensors. Additionally, we outline the ideal properties of GQDs, their eclectic methods of synthesis, and the general principle behind several biosensing techniques.DFG, 428780268, Biomimetische Rezeptoren auf NanoMIP-Basis zur Virenerkennung und -entfernung mittels integrierter Ansätz

Computational Studies on Functionalized ZnO Surfaces and Nanostructures

In this work, we have used computer simulations to investigate the effect of organic functionalization on ZnO surfaces and nanostructures. Density Functional Theory has been employed to study the interactions of ZnO surfaces with different organic groups, identifying stabilization mechanisms involved in each case and the most promising anchoring groups for ZnO functionalization. Additionally, a semi-empirical model for ZnO large scale simulations has been developed and validated by comparison against DFT calculations. The was successful in simulating Zn-containing bulk solids and molecular complexes, ZnO surfaces and nanostructures, and the adsorption of organic acids on (1010)-ZnO surfaces. We have also employed this model to characterize native defects in ZnO nanowires. Finally, we have demonstrated that the interaction of surface oxygen vacancies with organic acids may explain the suppression of photoluminescence anomalies observed for polymer coated ZnO nanowires

Silicon nanowire field-effect transistors for the detection of proteins

In this dissertation I present results on our efforts to increase the sensitivity and selectivity of silicon nanowire ion-sensitive field-effect transistors for the detection of biomarkers, as well as a novel method for wireless power transfer based on metamaterial rectennas for their potential use as implantable sensors. The sensing scheme is based on changes in the conductance of the semiconducting nanowires upon binding of charged entities to the surface, which induces a field-effect. Monitoring the differential conductance thus provides information of the selective binding of biological molecules of interest to previously covalently linked counterparts on the nanowire surface. In order to improve on the performance of the nanowire sensing, we devised and fabricated a nanowire Wheatstone bridge, which allows canceling out of signal drift due to thermal fluctuations and dynamics of fluid flow. We showed that balancing the bridge significantly improves the signal-to-noise ratio. Further, we demonstrated the sensing of novel melanoma biomarker TROY at clinically relevant concentrations and distinguished it from nonspecific binding by comparing the reaction kinetics. For increased sensitivity, an amplification method was employed using an enzyme which catalyzes a signal-generating reaction by changing the redox potential of a redox pair. In addition, we investigated the electric double layer, which forms around charges in an electrolytic solution. It causes electrostatic screening of the proteins of interest, which puts a fundamental limitation on the biomarker detection in solutions with high salt concentrations, such as blood. We solved the coupled Nernst-Planck and Poisson equations for the electrolyte under influence of an oscillating electric field and discovered oscillations of the counterion concentration at a characteristic frequency. In addition to exploring different methods for improved sensing capabilities, we studied an innovative method to supply power to implantable biosensors wirelessly, eliminating the need for batteries. A metamaterial split ring resonator is integrated with a rectifying circuit for efficient conversion of microwave radiation to direct electrical power. We studied the near-field behavior of this rectenna with respect to distance, polarization, power, and frequency. Using a 100 mW microwave power source, we demonstrated operating a simple silicon nanowire pH sensor with light indicator