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.

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.

Electrochemical Activation of Li2MnO3 Electrodes at 0 °C and Its Impact on the Subsequent Performance at Higher Temperatures.

This work continues our systematic study of Li- and Mn- rich cathodes for lithium-ion batteries. We chose Li2MnO3 as a model electrode material with the aim of correlating the improved electrochemical characteristics of these cathodes initially activated at 0 °C with the sstructural evolution of Li2MnO3, oxygen loss, formation of per-oxo like species (O22-) and the surface chemistry. It was established that performing a few initial charge/discharge (activation) cycles of Li2MnO3 at 0 °C resulted in increased discharge capacity and higher capacity retention, and decreased and substantially stabilized the voltage hysteresis upon subsequent cycling at 30 °C or at 45 °C. In contrast to the activation of Li2MnO3 at these higher temperatures, Li2MnO3 underwent step-by-step activation at 0 °C, providing a stepwise traversing of the voltage plateau at >4.5 V during initial cycling. Importantly, these findings agree well with our previous studies on the activation at 0 °C of 0.35Li2MnO3·0.65Li[Mn0.45Ni0.35Co0.20]O2 materials. The stability of the interface developed at 0 °C can be ascribed to the reduced interactions of the per-oxo-like species formed and the oxygen released from Li2MnO3 with solvents in ethylene carbonate-methyl-ethyl carbonate/LiPF6 solutions. Our TEM studies revealed that typically, upon initial cycling both at 0 °C and 30 °C, Li2MnO3 underwent partial structural layered-to-spinel (Li2Mn2O4) transition.

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.

Modification of Li- and Mn-Rich Cathode Materials via Formation of the Rock-Salt and Spinel Surface Layers for Steady and High-Rate Electrochemical Performances.

We demonstrate a novel surface modification of Li- and Mn-rich cathode materials 0.33Li2MnO3·0.67LiNi0.4Co0.2Mn0.4O2 for lithium-ion batteries (high-energy Ni-Co-Mn oxides, HE-NCM) via their heat treatment with trimesic acid (TA) or terephthalic acid at 600 °C under argon. We established the optimal regimes of the treatment-the amounts of HE-NCM, acid, temperature, and time-resulting in a significant improvement of the electrochemical behavior of cathodes in Li cells. It was shown that upon treatment, some lithium is leached out from the surface, leading to the formation of a surface layer comprising rock-salt-like phase Li0.4Ni1.6O2. The analysis of the structural and surface studies by X-ray diffraction, transmission electron microscopy, and X-ray photoelectron spectroscopy confirmed the formation of the above surface layer. We discuss the possible reactions of HE-NCM with the acids and the mechanism of the formation of the new phases, Li0.4Ni1.6O2 and spinel. The electrochemical characterizations were performed by testing the materials versus Li anodes at 30 °C. Importantly, the electrochemical results disclose significantly improved cycling stability (much lower capacity fading) and high-rate performance for the treated materials compared to the untreated ones. We established a lower evolution of the voltage hysteresis with cycling for the treated cathodes compared to that for the untreated ones. Thermal studies by differential scanning calorimetry also demonstrated lower (by ∼32%) total heat released in the reactions of the materials treated with fluoroethylene carbonate (FEC)-dimethyl carbonate (DEC)/LiPF6 electrolyte solutions, thus implying their significant surface stabilization because of the surface treatment. It was established by a postmortem analysis after 400 cycles that a lower amount of transition-metal cations dissolved (especially Ni) and a reduced number of surface cracks were formed for the 2 wt % TA-treated HE-NCMs compared to the untreated ones. We consider the proposed method of surface modification as a simple, cheap, and scalable approach to achieve a steady and superior electrochemical performance of HE-NCM cathodes.

Light-Controlled Selective Collection-and-Release of Biomolecules by an On-Chip Nanostructured Device.

The analysis of biosamples, e.g., blood, is a ubiquitous task of proteomics, genomics, and biosensing fields; yet, it still faces multiple challenges, one of the greatest being the selective separation and detection of target proteins from these complex biosamples. Here, we demonstrate the development of an on-chip light-triggered reusable nanostructured selective and quantitative protein separation and preconcentration platform for the direct analysis of complex biosamples. The on-chip selective separation of required protein analytes from raw biosamples is performed using antibody-photoacid-modified Si nanopillars vertical arrays (SiNPs) of ultralarge binding surface area and enormously high binding affinity, followed by the light-controlled rapid release of the tightly bound target proteins in a controlled liquid media. Two important experimental observations are presented: (1) the first demonstration on the control of biological reaction binding affinity by the nanostructuring of the capturing surface, leading to highly efficient protein collection capabilities, and (2) the light-triggered switching of the highly sticky binding surfaces into highly reflective nonbinding surfaces, leading to the rapid and quantitative release of the originally tightly bound protein species. Both of these two novel behaviors were theoretically and experimentally investigated. Importantly, this is the first demonstration of a three-dimensional (3D) SiNPs on-chip filter with ultralarge binding surface area and reversible light-controlled quantitative release of adsorbed biomolecules for direct purification of blood samples, able to selectively collect and separate specific low abundant proteins, while easily removing unwanted blood components (proteins, cells) and achieving desalting results, without the requirement of time-consuming centrifugation steps, the use of desalting membranes, or affinity columns.

Cellular Metabolomics by a Universal Redox-Reactive Nanosensors Array: From the Cell Level to Tumor-on-a-Chip Analysis.

Although biosensors based on nanowires-field effect transistor were proved extraordinarily efficient in fundamental applications, screening of charges due to the high-ionic strength of most physiological solutions imposes severe limitations in the design of smart, "real-time" sensors, as the biosample solution has to be previously desalted. This work describes the development of a novel nanowire biosensor that performs extracellular real-time multiplex sensing of small molecular metabolites, the true indicators of the body's chemistry machinery, without any preprocessing of the biosample. Unlike other nanoFET devices that follow direct binding of analytes to their surfaces, our nanodevice acts by sensing the oxidation state of redox-reactive chemical species bound to its surface. The device's surface array is chemically modified with a reversible redox molecular system that is sensitive to H2O2 down to 100 nM, coupled with a suite of corresponding oxidase enzymes that convert target metabolites to H2O2, enabling the direct prompt analysis of complex biosamples. This modality was successfully demonstrated for the real-time monitoring of cancer cell samples' metabolic activity and evaluating chemotherapeutic treatment options for cancer. This distinctive system displays ultrasensitive, selective, noninvasive, multiplex, real-time, label-free, and low-cost sensing of small molecular metabolites in ultrasmall volumes of complex biosamples, in the single-microliter scale, placing our technology at the forefront of this cutting-edge field.

Understanding the Role of Minor Molybdenum Doping in LiNi0.5Co0.2Mn0.3O2 Electrodes: from Structural and Surface Analyses and Theoretical Modeling to Practical Electrochemical Cells.

Doping LiNi0.5Co0.2Mn0.3O2 (NCM523) cathode material by small amount of Mo6+ ions, around 1 mol %, affects pronouncedly its structure, surface properties, and electronic and electrochemical behavior. Cathodes comprising Mo6+-doped NCM523 exhibited in Li cells higher specific capacities, higher rate capabilities, lower capacity fading, and lower charge-transfer resistance that relates to a more stable electrode/solution interface due to doping. This, in turn, is ascribed to the fact that the Mo6+ ions tend to concentrate more at the surface, as a result of a synthesis that always includes a necessary calcination, high-temperature stage. This phenomenon of the Mo dopant segregation at the surface in NCM523 material was discovered in the present work for the first time. It appears that Mo doping reduces the reactivity of the Ni-rich NCM cathode materials toward the standard electrolyte solutions of Li-ion batteries. Using density functional theory (DFT) calculations, we showed that Mo6+ ions are preferably incorporated at Ni sites and that the doping increases the amount of Ni2+ ions at the expense of Ni3+ ions, due to charge compensation, in accord with X-ray absorption fine structure (XAFS) spectroscopy measurements. Furthermore, DFT calculations predicted Ni-O bond length distributions in good agreement with the XAFS results, supporting a model of partial substitution of Ni sites by molybdenum.

Biorecognition layer engineering: overcoming screening limitations of nanowire-based FET devices.

Detection of biological species is of great importance to numerous areas of medical and life sciences from the diagnosis of diseases to the discovery of new drugs. Essential to the detection mechanism is the transduction of a signal associated with the specific recognition of biomolecules of interest. Nanowire-based electrical devices have been demonstrated as a powerful sensing platform for the highly sensitive detection of a wide-range of biological and chemical species. Yet, detecting biomolecules in complex biosamples of high ionic strength (>100 mM) is severely hampered by ionic screening effects. As a consequence, most of existing nanowire sensors operate under low ionic strength conditions, requiring ex situ biosample manipulation steps, that is, desalting processes. Here, we demonstrate an effective approach for the direct detection of biomolecules in untreated serum, based on the fragmentation of antibody-capturing units. Size-reduced antibody fragments permit the biorecognition event to occur in closer proximity to the nanowire surface, falling within the charge-sensitive Debye screening length. Furthermore, we explored the effect of antibody surface coverage on the resulting detection sensitivity limit under the high ionic strength conditions tested and found that lower antibody surface densities, in contrary to high antibody surface coverage, leads to devices of greater sensitivities. Thus, the direct and sensitive detection of proteins in untreated serum and blood samples was effectively performed down to the sub-pM concentration range without the requirement of biosamples manipulation.

Non-covalent monolayer-piercing anchoring of lipophilic nucleic acids: preparation, characterization, and sensing applications.

Functional interfaces of biomolecules and inorganic substrates like semiconductor materials are of utmost importance for the development of highly sensitive biosensors and microarray technology. However, there is still a lot of room for improving the techniques for immobilization of biomolecules, in particular nucleic acids and proteins. Conventional anchoring strategies rely on attaching biomacromolecules via complementary functional groups, appropriate bifunctional linker molecules, or non-covalent immobilization via electrostatic interactions. In this work, we demonstrate a facile, new, and general method for the reversible non-covalent attachment of amphiphilic DNA probes containing hydrophobic units attached to the nucleobases (lipid-DNA) onto SAM-modified gold electrodes, silicon semiconductor surfaces, and glass substrates. We show the anchoring of well-defined amounts of lipid-DNA onto the surface by insertion of their lipid tails into the hydrophobic monolayer structure. The surface coverage of DNA molecules can be conveniently controlled by modulating the initial concentration and incubation time. Further control over the DNA layer is afforded by the additional external stimulus of temperature. Heating the DNA-modified surfaces at temperatures >80 °C leads to the release of the lipid-DNA structures from the surface without harming the integrity of the hydrophobic SAMs. These supramolecular DNA layers can be further tuned by anchoring onto a mixed SAM containing hydrophobic molecules of different lengths, rather than a homogeneous SAM. Immobilization of lipid-DNA on such SAMs has revealed that the surface density of DNA probes is highly dependent on the composition of the surface layer and the structure of the lipid-DNA. The formation of the lipid-DNA sensing layers was monitored and characterized by numerous techniques including X-ray photoelectron spectroscopy, quartz crystal microbalance, ellipsometry, contact angle measurements, atomic force microscopy, and confocal fluorescence imaging. Finally, this new DNA modification strategy was applied for the sensing of target DNAs using silicon-nanowire field-effect transistor device arrays, showing a high degree of specificity toward the complementary DNA target, as well as single-base mismatch selectivity.

Electrochemical processes of nucleation and growth of calcium phosphate on titanium supported by real-time quartz crystal microbalance measurements and X-ray photoelectron spectroscopy analysis.

Real-time, in situ electrochemical quartz crystal microbalance (EQCM) measurements are conducted to better understand the electrocrystallization of calcium phosphates (CaP) on CP-Ti. X-ray photoelectron spectroscopy is used to identify the exact phase deposited, so that reliable estimation of the electrochemical processes involved is made. Analysis of the integrated intensity of the oxygen shake-up peaks, in combination with the determination of Ca/P and O/Ca atomic ratios, enables to determine unambiguously that the octacalcium phosphate (OCP) is formed. Its role as a precursor to hydroxyapatite (HAp) is discussed. After an incubation period, the process by which OCP is formed follows a Faradaic behavior. The incubation time may be related to the need for local increase of pH before precipitation from solution can occur. The standard enthalpy of activation is approximately 40 kJ/mol, which excludes diffusion-controlled processes from being rate determining. The OCP deposit has thickness approximately 0.61 microm, apparent density approximately 0.95 g/cm3, 63.6% porosity, and deposition rate of 23.5 ng/(cm2 s) or 15 nm/min. The low-equivalent weight value of 20.5 g/equiv, and the associated remarkably high number of electrons transferred in the reaction n approximately 24, indicates that most of the current is consumed either by electrolysis of water or by a complex set of parasitic reactions. The low-solubility product allows precipitation of CaP even at relatively low concentrations of calcium and phosphate/hydrogen phosphate ions. It is shown that HAp most likely forms via transformation of precursor phases, such as OCP, rather than directly.