Universal Approach to Direct Spatiotemporal Dynamic In Situ Optical Visualization of On-Catalyst Water Splitting Electrochemical Processes.

Electrochemical reactions are the unrivaled backbone of next-generation energy storage, energy conversion, and healthcare devices. However, the real-time visualization of electrochemical reactions remains the bottleneck for fully exploiting their intrinsic potential. Herein, for the first time, a universal approach to direct spatiotemporal-dynamic in situ optical visualization of pH-based as well as specific byproduct-based electrochemical reactions is performed. As a highly relevant and impactful example, in-operando optical visualization of on-catalyst water splitting processes is performed in neutral water/seawater. HPTS (8-hydroxypyrene-1,3,6-trisulfonicacid), known for its exceptional optical capability of detecting even the tiniest pH changes allows the unprecedented "spatiotemporal" real-time visualization at the electrodes. As a result, it is unprecedentedly revealed that at a critical cathode-to-anode distance, the bulk-electrolyte "self-neutralization" phenomenon can be achieved during the water splitting process, leading to the practical realization of enhanced additive-free neutral water splitting. Furthermore, it is experimentally unveiled that at increasing electrolyte flow rates, a swift and severe inhibition of the concomitantly forming acidic and basic 'fronts', developed at anode and cathode compartments are observed, thus acting as a "buffering" mechanism. To demonstrate the universal applicability of this elegant strategy which is not limited to pH changes, the technique is extended to visualization of hypochlorite/ chlorine at the anode during electrolysis of sea water using N-(4-butanoic acid) dansylsulfonamide (BADS). Thus, a unique experimental tool that allows real-time spatiotemporal visualization and simultaneous mechanistic investigation of complex electrochemical processes is developed that can be universally extended to various fields of research.

Buckling and fracture characterization of pristine bundles of vertically aligned carbon nanotubes using quantitativein situTEM axial compression.

This work investigates the mechanical deformation and fracture characteristics of pristine bundles of vertically aligned multi-walled carbon nanotubes (MWCNTs) subjected to axial compressionin situtransmission electron microscope (TEM). Accurate measurements of force-displacement data were collected simultaneously with real-time TEM videos of the deformation process. Two distinct regimes were observed in the force-displacement curve: (1) an initial elastic section with a linear slope, followed by (2) a transition to a force plateau at a critical buckling force. Morphological data revealed coordinated buckling of the pristine bundle, indicating strong van der Waals (VdW) forces between the nanotubes. The experimental setup measured an effective modulus of 83.9 GPa for an MWCNT bundle, which was in agreement with finite element analysis (FEA) simulations. FEA also highlighted the significant role of VdW forces in the bundle mechanical reactions. Furthermore, we identified nickel nanoparticles as key players in the fracture behavior of the bundles, acting as nucleation sites for defects. The direct mechanical measurements of MWCNT bundles provide valuable insights into their mechanical deformation and fracture behavior, while correlating it to the morphology of the bundle. Understanding these interactions at the bundle level is crucial for improving the reliability and durability of VACNTs-based components.

A novel, accurate, and non-invasive liquid biopsy test to measure cellular immune responses as a tool to diagnose early-stage lung cancer: a clinical trials study.

INTRODUCTION: Lung cancer remains the leading cause of death from cancer, worldwide. Developing early detection diagnostic methods, especially non-invasive methods, is a critical component to raising the overall survival rate and prognosis for lung cancer. The purpose of this study is to evaluate two protocols of a novel in vitro cellular immune response test to detect lung cancer. The test specifically quantifies the glycolysis metabolism pathway, which is a biomarker for the activation level of immune cells. It summarizes the results of two clinical trials, where each deploys a different protocol's version of this test for the detection of lung cancer. In the later clinical trial, an improved test protocol is applied. METHOD: The test platform is based on changes in the metabolic pathways of the immune cells following their activation by antigenic stimuli associated with Lung cancer. Peripheral Blood Mononuclear Cells are loaded on a multiwell plate together with various lung tumor associated antigens and a fluorescent probe that exhibits a pH-dependent absorption shift. The acidification process in the extracellular fluid is monitored by a commercial fluorescence plate reader device in continuous reading for 3 h at 37 °C to document the fluorescent signal received from each well. RESULTS: In the later clinical trial, an improved test protocol was applied and resulted in increased test accuracy. Specificity of the test increased to 94.0% and test sensitivity increased to 97.3% in lung cancer stage I, by using the improved protocol. CONCLUSION: The improved protocol of the novel cellular immune metabolic response based test detects stage I and stage II of lung cancer with high specificity and sensitivity, with low material costs and fast results.

Cyclic Buckling Characterization of an Individual MWCNT Using Quantitative In Situ TEM Axial Compression.

Carbon nanotubes (CNTs) are extremely conductive and flexible, making them ideal for applications such as flexible electronics and nanoelectromechanical systems. However, in order to properly apply them in such devices, their long-term durability must be assessed. In the present study, we demonstrate cyclic loading of a thick MWCNT (175 nm) under axial compression, observed in situ under a transmission electron microscope (TEM). The force was applied via controlled displacement, while real-time TEM videos of the deformation process were gathered to produce the morphological data. The in situ observations combined with force-displacement curves revealed the onset of buckling instabilities, and the elastic limits of the tube were assessed. The MWCNT retained its original structure even after 68 loading-unloading cycles, despite observed clues for structural distortions. The stiffness of the tube, calculated after each loading cycle, was in a 0.15 to 0.28 TPa range-comparable to the literature, which further validates the measurement set-up. These in situ tests demonstrate the resilience of CNTs to fatigue which can be correlated with the CNTs' structure. Such correlations can help tailoring CNTs' properties to specific applications.

Electronic Structure Engineering of Highly-Scalable Earth-Abundant Multi-Synergized Electrocatalyst for Exceptional Overall Water Splitting in Neutral Medium.

Efficient neutral water splitting may represent in future a sustainable solution to unconstrained energy requirements, but yet necessitates the development of innovative avenues for achieving the currently unmet required performances. Herein, a novel paradigm based on the combination of electronic structure engineering and surface morphology tuning of earth-abundant 3D-hierarchical binder-free electrocatalysts is demonstrated, via a scalable single-step thermal transformation of nickel substrates under sulfur environment. A temporal-evolution of the resulting 3D-nanostructured substrates is performed for the intentional enhancement of non-abundant highly-catalytic Ni3+ and pSn 2- species on the catalyst surface, concomitantly accompanied with densification of the hierarchical catalyst morphology. Remarkably, the finely engineered NiSx catalyst synthesized via thermal-evolution for 24 h (NiSx -24 h) exhibits an exceptionally low cell voltage of 1.59 V (lower than Pt/C-IrO2  catalytic couple) for neutral water splitting, which represents the lowest value ever reported. The enhanced performance of NiSx -24 h is a multi-synergized consequence of the simultaneous enrichment of oxygen and hydrogen evolution reaction catalyzing species, accompanied by an optimum electrocatalytic surface area and intrinsic high conductivity. Overall, this innovative work opens a route to engineering the active material's electronic structure/morphology, demonstrating novel Ni3+ /pSn 2- -enriched NiSx catalysts which surpass state-of-the-art materials for neutral water splitting.

Ultrafast one-minute electronic detection of SARS-CoV-2 infection by 3CLpro enzymatic activity in untreated saliva samples.

Since its onset in December 2019, severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, has caused over 6.5 million deaths worldwide as of October 2022. Attempts to curb viral transmission rely heavily on reliable testing to detect infections since a large number of transmissions are carried through asymptomatic individuals. Many available detection methods fall short in terms of reliability or point-of-care applicability. Here, we report an electrochemical approach targeting a viral proteolytic enzyme, 3CLpro, as a marker of active infection. We detect proteolytic activity directly from untreated saliva within one minute of sample incubation using a reduction-oxidation pH indicator. Importantly, clinical tests of saliva samples from 50 subjects show accurate detection of SARS-CoV-2, with high sensitivity and specificity, validated by PCR testing. These, coupled with our platform's ultrafast detection, simplicity, low cost and point-of-care compatibility, make it a promising method for the real-world SARS-CoV-2 mass-screening.

The "Bloodless" Blood Test: Intradermal Prick Nanoelectronics for the Blood Extraction-Free Multiplex Detection of Protein Biomarkers.

Protein biomarkers' detection is of utmost importance for preventive medicine and early detection of illnesses. Today, their detection relies entirely on clinical tests consisting of painful, invasive extraction of large volumes of venous blood; time-consuming postextraction sample manipulation procedures; and mostly label-based complex detection approaches. Here, we report on a point-of-care (POC) diagnosis paradigm based on the application of intradermal finger prick-based electronic nanosensors arrays for protein biomarkers' direct detection and quantification down to the sub-pM range, without the need for blood extraction and sample manipulation steps. The nanobioelectronic array performs biomarker sensing by a rapid intradermal prick-based sampling of proteins biomarkers directly from the capillary blood pool accumulating at the site of the microneedle puncture, requiring only 2 min and less than one microliter of a blood sample for a complete analysis. A 1 mm long microneedle element was optimal in allowing for pain-free dermal sampling with a 100% success rate of reaching and rupturing dermis capillaries. Current common micromachining processes and top-down fabrication techniques allow the nanobioelectronic sensor arrays to provide accurate and reliable clinical diagnostic results using multiple sensing elements in each microneedle and all-in-one direct and label-free multiplex biomarkers detection. Preliminary successful clinical studies performed on human volunteers demonstrated the ability of our intradermal, in-skin, blood extraction-free detection platform to accurately detect protein biomarkers as a plausible POC detection for future replacement of today's invasive clinical blood tests. This approach can be readily extended in the future to detect other clinically relevant circulating biomarkers, such as miRNAs, free-DNAs, exosomes, and small metabolites.

Three-Dimensional Monolithically Self-Grown Metal Oxide Highly Dense Nanonetworks as Free-Standing High-Capacity Anodes for Lithium-Ion Batteries.

Transition metal oxides (TMOs) have been widely studied as potential next-generation anode materials, owing to their high theoretical gravimetric capacity. However, to date, these anodes syntheses are plagued with time-consuming preparation processes, two-dimensional electrode fabrication, binder requirements, and short operational cycling lives. Here, we present a scalable single-step reagentless process for the synthesis of highly dense Mn3O4-based nanonetwork anodes based on a simple thermal treatment transformation of low-grade steel substrates. The monolithic solid-state chemical self-transformation of the steel substrate results in a highly dense forest of Mn3O4 nanowires, which transforms the electrochemically inactive steel substrate into an electrochemically highly active anode. The proposed method, beyond greatly improving the current TMO performance, surpasses state-of-the-art commercial silicon anodes in terms of capacity and stability. The three-dimensional self-standing anode exhibits remarkably high capacities (>1500 mA h/g), a stable cycle life (>650 cycles), high Coulombic efficiencies (>99.5%), fast rate performance (>1.5 C), and high areal capacities (>2.5 mA h/cm2). This novel experimental paradigm acts as a milestone for next-generation anode materials in lithium-ion batteries, and pioneers a universal method to transform different kinds of widely available, low-cost, steel substrates into electrochemically active, free-standing anodes and allows for the massive reduction of anode production complexity and costs.

Single-Step Solid-State Scalable Transformation of Ni-Based Substrates to High-Oxidation State Nickel Sulfide Nanoplate Arrays as Exceptional Bifunctional Electrocatalyst for Overall Water Splitting.

Hydrogen, undoubtedly the next-generation fuel for supplying the world's energy demands, needs economically scalable bifunctional electrocatalysts for its sustainable production. Non-noble transition metal-based electrocatalysts are considered an economic solution for water splitting applications. A single-step solid-state approach for the economically scalable transformation of Ni-based substrates into single-crystalline nickel sulfide nanoplate arrays is developed. X-ray diffraction and transmission electron microscopy measurements reveal the influence of the transformation temperature on the crystal growth direction, which in turn can manipulate the chemical state at the catalyst surface. Ni-based sulfide formed at 450 °C exhibits an enhanced concentration of electrocatalytically-active Ni3+ at their surface and a reduced electron density around sulfur atoms, optimal for efficient H2 production. The Ni-based sulfide electrocatalysts display exceptional electrocatalytic performance for both oxygen and hydrogen evolution, with overpotentials of 170 and 90 mV respectively. Remarkably, the two-electrode cell for overall electrolysis of alkaline water demonstrates an ultra-low cell potential of 1.46 V at 10 mA cm-2 and 1.69 V at 100 mA cm-2 . In addition to the exceptionally low water-splitting cell voltage, this self-standing electrocatalyst is of binderfree nature, with the electrode preparation being a low-cost and single-step process, easily scalable to industrial scales.

Depletion of Highly Abundant Protein Species from Biosamples by the Use of a Branched Silicon Nanopillar On-Chip Platform.

Highly abundant serum proteins tend to mask the low- and ultralow-abundance proteins, making low-abundance species detection extremely challenging. While traditional highly abundant protein depletion techniques are effective, they suffer from nonspecific binding problems and laborious sample manipulation procedures, and the kinetics of release of current separation systems is inadequately long, causing dilution of the eluted low-abundance protein samples. Here, we introduce an on-chip light-controlled reusable platform for the direct and fast depletion of highly abundant proteins from serum biosamples. Our nanoarrays display fast and highly selective depletion capabilities, up to 99% depletion of highly abundant protein species, with no undesired depletion effects on the concentration of low-abundance protein biomarkers. Displaying an ultrahigh surface area, ∼3400 m2 g-1, alongside a light-triggerable ultrafast release, this platform allows for a high depletion performance, together with high-yield reusability capabilities. Furthermore, this nanostructured light-controlled separation device could easily be integrated with downstream analytical technologies in a single lab-on-a-chip platform.

Clinic-on-a-Needle Array toward Future Minimally Invasive Wearable Artificial Pancreas Applications.

In order to reduce medical facility overload due to the rise of the elderly population, modern lifestyle diseases, or pandemics, the medical industry is currently developing point-of-care and home medical device systems. Diabetes is an incurable and lifetime disease, accountable for a significant mortality and socio-economic public health burden. Thus, tight glucose control in diabetic patients, which can prevent the onset of its late complications, is of enormous importance. Despite recent advances, the current best achievable management of glucose control is still inadequate, due to several key limitations in the system components, mainly related to the reliability of sensing components, both temporally and chemically, and the integration of sensing and delivery components in a single wearable platform, which is yet to be achieved. Thus, advanced closed-loop artificial pancreas systems able to modulate insulin delivery according to the measured sensor glucose levels, independently of patient supervision, represent a key requirement of development efforts. Here, we demonstrate a minimally invasive, transdermal, multiplex, and versatile continuous metabolites monitoring system in the subcutaneous interstitial fluid space based on a chemically modified SiNW-FET nanosensor array on microneedle elements. Using this technology, ISF-borne metabolites require no extraction and are measured directly and continuously by the nanosensors. Due to their chemical sensing mechanism, the nanosensor response is only influenced by the specific metabolite of interest, and no response is observed in the presence of potential exogenous and endogenous interferents known to seriously affect the response of current electrochemical glucose detection approaches. The 2D architecture of this platform, using a single SOI substrate as a top-down multipurpose material, resulted in a standard fabricated chip with 3D functionality. After proving the ability of the system to act as a selective multimetabolites sensor, we have implemented our platform to reach our main goal for in vivo continuous glucose monitoring of healthy human subjects. Furthermore, minor adjustments to the fabrication technique allow the on-chip integration of microinjection needle elements, which can ideally be used as a drug delivery system. Preliminary experiments on a mice animal model successfully demonstrated the single-chip capability to both monitor glucose levels as well as deliver insulin. By that, we hope to provide in the future a cost-effective and reliable wearable personalized clinical tool for patients and a strong tool for research, which will be able to perform direct monitoring of clinical biomarkers in the ISF as well as synchronized transdermal drug delivery by this single-chip multifunctional platform.

Optically transparent vertical silicon nanowire arrays for live-cell imaging.

Programmable nano-bio interfaces driven by tuneable vertically configured nanostructures have recently emerged as a powerful tool for cellular manipulations and interrogations. Such interfaces have strong potential for ground-breaking advances, particularly in cellular nanobiotechnology and mechanobiology. However, the opaque nature of many nanostructured surfaces makes non-destructive, live-cell characterization of cellular behavior on vertically aligned nanostructures challenging to observe. Here, a new nanofabrication route is proposed that enables harvesting of vertically aligned silicon (Si) nanowires and their subsequent transfer onto an optically transparent substrate, with high efficiency and without artefacts. We demonstrate the potential of this route for efficient live-cell phase contrast imaging and subsequent characterization of cells growing on vertically aligned Si nanowires. This approach provides the first opportunity to understand dynamic cellular responses to a cell-nanowire interface, and thus has the potential to inform the design of future nanoscale cellular manipulation technologies.

Rapid Collection and Aptamer-Based Sensitive Electrochemical Detection of Soybean Rust Fungi Airborne Urediniospores.

Plants are the central source of food for humans around the world. Unfortunately, plants can be negatively affected by diverse kinds of diseases that are responsible for major economic losses worldwide. Thus, monitoring plant health and early detection of pathogens are essential to reduce disease spread and facilitate effective management practices. Various detection approaches are currently practiced. These methods mainly include visual inspection and laboratory tests. Nonetheless, these methods are labor-intensive, time-consuming, expensive, and inefficient in the early stages of infection. Thus, it is extremely important to detect diseases at the early stages of the epidemic. Here, we would like to present a fast, sensitive, and reliable electrochemical sensing platform for the detection of airborne soybean rust spores. The suspected airborne soybean rust spores are first collected and trapped inside a carbon 3D electrode matrix by high-capacity air-sampling means. Then, a specific biotinylated aptamer, suitable to target specific sites of soybean rust spores is applied. This aptamer agent binds to the surface of the collected spores on the electrode. Finally, spore-bound aptamer units are incubated with a streptavidin-alkaline phosphatase agent leading to the enzymatic formation of p-nitrophenol, which is characterized by its unique electrochemical properties. Our method allows for the rapid (ca. 2 min), selective, and sensitive collection and detection of soybean rust spores (down to the limit of 100-200 collected spores per cm2 of electrode area). This method could be further optimized for its sensitivity and applied to the future multiplex early detection of various airborne plant diseases.

Diversely Doped Uniform Silicon Nanotube Axial Heterostructures Enabled by "Dopant Reflection".

Here, we propose a novel method for the synthesis of extremely uniform, diversely doped silicon nanotube heterostructures. The method, comprising a simple two-step synthesis, exploits the use of a Ge nanowire sacrificial core upon which a multidoping axial pattern can be easily obtained, that is enclosed in an intrinsic Si shell. The Ge-Si core-shell structure is then heated to 750 °C, allowing the migration of dopant elements from the Ge core directly into the Si shell. Removal of the Ge core, via either wet or dry etch, does not impair the crystallinity of the Si shell nor its electrical characteristics, allowing for the formation of a multidoped axially patterned, conformal, and uniform Si nanotube. The precise dopant patterning allows for the extension of Si nanotube applications, which were unattainable because of the inability to precisely control the parameters and uniformity of the nanotubes while doping the structure simultaneously.

Ultrafast high-capacity capture and release of uranium by a light-switchable nanotextured surface.

Nuclear power is growing in demand as a promising sustainable energy source, its most prevalent source being uranium salts. The resulting processing and transportation of uranium raise concerns regarding the environmental impact and risks for human health. Close proximity to uranium mines puts populations at higher risk for exposure due to elevated uranium concentrations. As the main form of uranium in aqueous solutions, uranyl (UO2 2+) has been the focus of many methods of uranium sieving; most fall short by being time-consuming or lacking a retrieval mechanism for the captured uranium. Here, we demonstrate the ultrafast and selective uranyl-capturing properties of aptamer-modified branched silicon nanopillar (BSiNP) arrays. Our nanostructured surfaces demonstrate an ultrahigh surface area modified with a uranyl-specific DNA aptamer, allowing for high uranyl-capturing capacity, reaching up to 550 mg g-1. Uranyl capture is followed by the activation of a covalently bonded photoacid, causing a light-triggerable, ultrafast release. This capture-and-release cycle results in the collection of over 70% of the uranium found in the original samples within less than one hour.

Synthesis and electrochemical performance of silicon-nanowire alloy anodes.

High-capacity materials are required in order to address the environmental concerns of our modern society, ultimately leading to safe and eco-friendly high-energy batteries. Silicon-nanowire anodes (SiNWs) have the potential to significantly increase the energy density of lithium-ion batteries (LIBs). In order to improve the mechanical durability and the electrochemical performance of SiNW-anodes, we fabricated a silicon-nickel (SiNi) composite anode by electroless deposition of nickel, followed by annealing at high temperature to obtain nickel silicides of different content and composition. The morphology of SiNi-alloy anodes was examined by SEM, in situ TEM and EDS methods in order to understand how different deposition protocols affect the coating of the silicon nanowires. The formation of Ni-silicides was found to occur during thermal treatment at 900 °C. Despite the incomplete shell coverage of SiNWs composed of multiple phases and grains, the electrochemical performance of binder-free and conducting-additive-free SiNi-alloy anodes showed stable electrochemical behavior and higher capacity retention compared to the pristine SiNW anode. Li/SiNW-SiNi x cells ran at C/2 rate for 200 reversible cycles, exhibiting 0.1%/cycle capacity loss after completion of the SEI formation.

Direct whole blood analysis by the antigen-antibody chemically-delayed dissociation from nanosensors arrays.

A wide range of fields, starting from basic research in life sciences and up to medical applications, are highly interested in the investigation and detection of biomarkers in all their forms, including proteins. However, direct analytical detection of specific protein biomarkers from a physiological biosample is still extremely challenging due to the abundant variety and amount of its components. In this work, we apply the chemically-controlled antigen-dissociation detection approach on silicon nanowires-based field-effect transistor arrays, by creating a suitable 'chemical environment' which enabled the clear-cut splitting of the dissociation regime window into two sub-regimes, thus allowing the complete washing of the nonspecifically adsorbed salts and biomolecules, while significantly delaying the dissociation of specific surface-bounded antigen-antibody pairs. This was accomplished by the addition of the water-miscible organic reagent ethylene glycol, which radically alters the properties of the aqueous solvent, by means of dramatically reducing its interactions with the particular protein antigen, and thus allowing for the increase in the antigen-antibody interaction strength. This in turn, deeply reduces the solubility of the surface-bound protein molecules and increases their interaction with the specific receptor antibody units, which brings to a substantial delay in the antibody-antigen dissociation behavior. This phenomenon allows the clear-cut splitting of the dissociation regime window and the quantitative and accurate analysis of proteins in physiological samples. We demonstrated the direct and quantitative detection of protein biomarkers, down to concentrations in the fM range, from unprocessed whole blood minuscule samples of only a few microliters. This work is the first demonstration on the chemically-controlled dissociation kinetics of antibody-antigen pairs by the use of water-miscible organic solvent mixtures, and its application in the direct ultrasensitive detection of protein biomarkers from whole blood samples.

Direct Detection of Uranyl in Urine by Dissociation from Aptamer-Modified Nanosensor Arrays.

An ever-growing demand for uranium in various industries raises concern for human health of both occupationally exposed personnel and the general population. Toxicological effects related to uranium (natural, enriched, or depleted uranium) intake involve renal, pulmonary, neurological, skeletal, and hepatic damage. Absorbed uranium is filtered by the kidneys and excreted in the urine, thus making uranium detection in urine a primary indication for exposure and body burden assessment. Therefore, the detection of uranium contamination in bio-samples (urine, blood, saliva, etc.,) is of crucial importance in the field of occupational exposure and human health-related applications, as well as in nuclear forensics. However, the direct determination of uranium in bio-samples is challenging because of "ultra-low" concentrations of uranium, inherent matrix complexity, and sample diversity, which pose a great analytical challenge to existing detection methods. Here, we report on the direct, real-time, sensitive, and selective detection of uranyl ions in unprocessed and undiluted urine samples using a uranyl-binding aptamer-modified silicon nanowire-based field-effect transistor (SiNW-FET) biosensor, with a detection limit in the picomolar concentration range. The aptamer-modified SiNW-FET presented in this work enables the simple and sensitive detection of uranyl in urine samples. The experimental approach has a straight-forward implementation to other metals and toxic elements, given the availability of target-specific aptamers. Combining the high surface-to-volume ratio of SiNWs, the high affinity and selectivity of the uranyl-binding aptamer, and the distinctive sensing methodology gives rise to a practical platform, offering simple and straightforward sensing of uranyl levels in urine, suitable for field deployment and point-of-care applications.

Real-time monitoring of bacterial biofilms metabolic activity by a redox-reactive nanosensors array.

BACKGROUND: Bacterial biofilms are communities of surface-associated microorganisms living in cellular clusters or micro-colonies, encapsulated in a complex matrix composed of an extracellular polymeric substance, separated by open water channels that act as a circulatory system that enable better diffusion of nutrients and easier removal of metabolic waste products. The monitoring of biofilms can provide important information on fundamental biofilm-related processes. That information can shed light on the bacterial processes and enable scientists to find ways of preventing future bacterial infections. Various approaches in use for biofilm analysis are based on microscopic, spectrochemical, electrochemical, and piezoelectrical methods. All these methods provide significant progress in understanding the bio-process related to biofilm formation and eradication, nevertheless, the development of novel approaches for the real-time monitoring of biochemical, in particular metabolic activity, of bacterial species during the formation, life and eradication of biofilms is of great potential importance. RESULTS: Here, detection and monitoring of the metabolic activity of bacterial biofilms in high-ionic-strength solutions were enabled as a result of novel surface modification by an active redox system, composed of 9,10-dihydroxyanthracene/9,10-anthraquinone, on the oxide layer of the SiNW, yielding a chemically-gated FET array. With the use of enzymatic reactions of oxidases, metabolites can be converted to H2O2 and monitored by the nanosensors. Here, the successful detection of glucose metabolites in high-ionic-strength solutions, such as bacterial media, without pre-processing of small volume samples under different conditions and treatments, has been demonstrated. The biofilms were treated with antibiotics differing in their mechanisms of action and were compared to untreated biofilms. Further examination of biofilms under antibiotic treatment with SiNW-FET devices could shed light on the bioprocess that occurs within the biofilm. Moreover, finding proper treatment that eliminates the biofilm could be examined by the novel nanosensor as a monitoring tool. CONCLUSIONS: To summarize, the combination of redox-reactive SiNW-FET devices with micro-fluidic techniques enables the performance of rapid, automated, and real-time metabolite detection with the use of minimal sample size, noninvasively and label-free. This novel platform can be used as an extremely sensitive tool for detection and establishing medical solutions for bacterial-biofilm eradication and for finding a proper treatment to eliminate biofilm contaminations. Moreover, the sensing system can be used as a research tool for further understanding of the metabolic processes that occur within the bacterial biofilm population.

Redox-Reactive Field-Effect Transistor Nanodevices for the Direct Monitoring of Small Metabolites in Biofluids toward Implantable Nanosensors Arrays.

Chemically modified field-effect transistor (FET) nanodevices were shown to be a selective and extremely sensitive detection platform. In FET-based sensors, signal amplification and transduction is based on electrostatic gating of the nanometric semiconductor channel by analyte-receptor interactions, which measurably affect the transconductance of the device. However, chemically modified FETs must overcome several fundamental limitations before they can be effectively deployed as real-time sensors for bioevents occurring on their surface in complex biofluids. Here, we demonstrate the development of amperoFET devices for the real-time continuous monitoring of small molecular metabolites in biofluids. The surface of the nanowires is covalently modified with a redox reversible moiety, which is easily oxidized in the presence of H2O2. The reversible redox transformation of the surface-confined molecules is carried out by a hot electron injection mechanism, conducted simply by the modulation of the source-drain current through the nanoFET sensing device. By this approach, electrons may be injected by the nanowire element into the surface-confined redox moiety and thus maintain a whole-electrically actuated redox system in which the oxidation state is completely controlled by the current applied to the amperoFET system. The modulation of the source-drain current allows the control of the reduced versus oxidized redox moieties population on the nanowire surface, and this, in turn, is applied as the main sensing mechanism. At a given constant source-drain and gate voltage, the chemical perturbation exerted by the presence of chemical oxidants in the tested biofluid will lead to a measurable conductance change. Alteration in the concentration of the specific metabolite will chemically regulate the extent of perturbation applied to the redox system, which can be utilized for the quantification of the molecular metabolite of interest. These 'equilibrium'-type sensors are fully electrically operated and can be further used in implantable sensing applications.