Rapid tool for cell nanoarchitecture integrity assessment.

With the rapid increase and accessibility of high-resolution imaging technologies of cells, the interpretation of results relies more and more on the assumption that the three-dimensional integrity of the surrounding cellular landscape is not compromised by the experimental setup. However, the only available technology for directly probing the structural integrity of whole-cell preparations at the nanoscale is electron cryo-tomography, which is time-consuming, costly, and complex. We devised an accessible, inexpensive and reliable screening assay to quickly report on the compatibility of experimental protocols with preserving the structural integrity of whole-cell preparations at the nanoscale. Our Rapid Cell Integrity Assessment (RCIA) assay is executed at room temperature and relies solely on light microscopy imaging. Using cellular electron cryo-tomography as a benchmark, we verify that RCIA accurately unveils the adverse impact of reagents and/or protocols such as those used for virus inactivation or to arrest dynamic processes on the cellular nanoarchitecture.

Low-cost flexible plasmonic nanobump metasurfaces for label-free sensing of serum tumor marker.

The use of plasmonic metasurface for sensing has great potential on label-free detection of human tumor markers, which could benefit clinical examination. In this work, we adopt nanoimprint and plasma etching to optimize the nanofabrication for low-cost flexible plasmonic metasurface sensors with gold nanobump arrays, which enable facile surface bio-functionality, high sensitivity and simple optical measurement in the visible range. A high bulk refractive index sensitivity of 454.4 nm/RIU is achieved for the prototype plasmonic metasurface sensors at the wavelengths from 620 nm to 720 nm. The rapid quantitative tumor marker sensing of carcinoembryonic antigen in human serum samples from less than 10 ng/mL to more than 87 ng/mL is achieved, which demonstrates good agreement with the conventional chemiluminescence immunoassay system and sufficiently covers the threshold tumor marker concentration of 20 ng/mL for early cancer prediction. Our method is capable of low-cost high-throughput manufacturing for flexible lightweight plasmonic metasurface sensors, which will facilitate wide applications on portable biomedical sensing devices for future point-of-care diagnosis and mobile healthcare.

Nano-Fe3C@PGC as a novel low-cost anode electrocatalyst for superior performance microbial fuel cells.

We report a novel anode electrocatalyst, iron carbide nanoparticles dispersed in porous graphitized carbon (Nano-Fe3C@PGC), which is synthesized by facile approach involving a direct pyrolysis of ferrous gluconate and a following removal of free iron, but provides microbial fuel cells with superior performances. The physical characterizations confirm the unique configuration of iron carbide nanoparticles with porous graphitized carbon. Electrochemical measurements demonstrate that the as-synthesized Nano-Fe3C@PGC exhibits an outstanding electrocatalytic activity toward the charge transfer between bacteria and anode. Equipped with Nano-Fe3C@PGC, the microbial fuel cells based on a mixed bacterium culture yields a power density of 1856 mW m-2. The resulting excellent performance is attributed to the large electrochemical active area and the high electronic conductivity that porous graphitized carbon provides and the enriched electrochemically active microorganisms and enhanced activity towards the redox reactions in microorganisms by Fe3C nanoparticles.

Ex Vivo and In Vivo Biocompatibility Assessment (Blood and Tissue) of Three-Dimensional Bacterial Nanocellulose Biomaterials for Soft Tissue Implants.

Bacterial nanocellulose (BNC) is a promising biomedical material. However, the haemocompatibility (haemolysis and thrombogenicity) and acute and sub-chronic immune responses to three-dimensional (3D) BNC biomaterials have not been evaluated. Accordingly, this manuscript focused on the effect of 3D microporosity on BNC haemocompatibility and a comparison with 2D BNC architecture, followed by the evaluation of the immune response to 3D BNC. Blood ex vivo studies indicated that compared with other 2D and 3D BNC architectures, never-dried 2D BNC presented antihemolytic and antithrombogenic effects. Nevertheless, in vivo studies indicated that 3D BNC did not interfere with wound haemostasis and elicited a mild acute inflammatory response, not a foreign body or chronic inflammatory response. Moreover, compared with the polyethylene controls, the implant design with micropores ca. 60 µm in diameter showed a high level of collagen, neovascularization and low fibrosis. Cell/tissue infiltration increased to 91% after 12 weeks and was characterized by fibroblastic, capillary and extracellular matrix infiltration. Accordingly, 3D BNC biomaterials can be considered a potential implantable biomaterial for soft tissue augmentation or replacement.

Multidimensional (0D-3D) nanostructures for lung cancer biomarker analysis: Comprehensive assessment on current diagnostics.

The pragmatic outcome of a lung cancer diagnosis is closely interrelated in reducing the number of fatal death caused by the world's top cancerous disease. Regardless of the advancement made in understanding lung tumor, and its multimodal treatment, in general the percentage of survival remain low. Late diagnosis of a cancerous cell in patients is the major hurdle for the above circumstances. In the new era of a lung cancer diagnosis with low cost, portable and non-invasive clinical sampling, nanotechnology is at its inflection point where current researches focus on the implementation of biosensor conjugated nanomaterials for the generation of the ideal sensing. The present review encloses the superiority of nanomaterials from zero to three-dimensional nanostructures in its discrete and nanocomposites nanotopography on sensing lung cancer biomarkers. Recent researches conducted on definitive nanomaterials and nanocomposites at multiple dimension with distinctive physiochemical property were focused to subside the cases associated with lung cancer through the development of novel biosensors. The hurdles encountered in the recent research and future preference with prognostic clinical lung cancer diagnosis using multidimensional nanomaterials and its composites are presented.

Xerogel based catalyst for improved cathode performance in microbial fuel cells.

In a microbial fuel cell (MFC) the reduction reaction at cathode has been a limiting factor in achieving maximum power density, and numerous strategies have been implemented in an attempt to overcome this. Herein, we demonstrate that carbon xerogel (CX) doped with iron (Fe) and nitrogen (N) followed by modification with graphene oxide (GO) is an efficient catalyst for MFCs. The CXFeNGO catalyst was characterized using a scanning electron microscope, and X-ray diffraction, and the catalytic activity was confirmed using cyclic voltammetry studies. At the anode, colonization of bacterial cells on the electrode surface, forming a biofilm, was observed. When the CXFeNGO-modified electrode was used at the cathode in the MFC, a maximum power density of 176.5 ± 6 mW m-2 was obtained, compared to that of plain graphite electrode, which produced 139.1 ± 4 mW m-2. The power density of the modified electrode is thus 26.8% higher. The power density further increased to 48.6% when the pH of the catholyte was increased to 12, producing a power density of 207 ± 4 mW m-2.

Self-Propelled Micro/Nanomotors for Sensing and Environmental Remediation.

Self-propelled micro/nanomotors have gained attention for successful application in cargo delivery, therapeutic treatments, sensing, and environmental remediation. Unique characteristics such as high speed, motion control, selectivity, and functionability promote the application of micro/nanomotors in analytical sciences. Here, the recent advancements and main challenges regarding the application of self-propelled micro/nanomotors in sensing and environmental remediation are discussed. The current state of micro/nanomotors is reviewed, emphasizing the period of the last five years, then their developments into the future applications for enhanced sensing and efficient purification of water resources are extrapolated.

Multifunctional Self-Assembling Peptide-Based Nanostructures for Targeted Intracellular Delivery: Design, Physicochemical Characterization, and Biological Assessment.

Peptide amphiphiles (PAs), consisting of a hydrophobic alkyl chain covalently bound to a hydrophilic peptide sequence, possess a versatile molecular design due to their combined self-assembling features of amphiphile surfactants and biological functionalities of peptides. Through rational design, PAs can self-assemble into a variety of nanostructures with controlled shape, size, and biological functionality to deliver therapeutic and imaging agents to target cells. Here, we describe principles to design multifunctional PAs for self-assembly into micellar nanostructures and targeted intracellular delivery. The PA micelles are designed to display a tumour targeting sequence on their surfaces and direct their interactions with specific cells. This targeting sequence includes an enzymatic sensitive sequence that can be cleaved upon exposure to matrix metalloproteinase 2 (MMP-2), an enzyme overexpressed in tumor environment, allowing the presentation of a cell-penetrating domain. The presentation of this domain will then facilitate the delivery of therapeutics for cancer treatment inside targeted cells. Methods to characterize the key physicochemical properties of PAs and their assemblies, including secondary structure, critical micelle concentration, shape and size, are described in detail. The enzyme responsiveness of PA assemblies is described with respect to their degradation by MMP-2. Protocols to evaluate the cytotoxicity and cellular uptake of the micellar carriers are also included.

Electrically-receptive and thermally-responsive paper-based sensor chip for rapid detection of bacterial cells.

Although significant technological advancements have been made in the development of analytical biosensor chips for detecting bacterial strains (E. coli, S. Mutans and B. Subtilis), critical requirements i.e. limit of detection (LOD), fast time of response, ultra-sensitivity with high reproducibility and good shelf-life with robust sensing capability have yet to be met within a single sensor chip. In order to achieve these criteria, we present an electrically-receptive thermally-responsive (ER-TR) sensor chip comprised of simple filter paper used as substrate coated with composite of poly(N-isopropylacrylamide) polymer (PNIPAm) - graphene nanoplatelet (GR) followed by evaporation of Au electrodes for capturing both Gram-positive (S. mutans and B. subtilis) and Gram-negative (E. coli) bacterial cells in real-time. Autoclave water, tap water, lake water and milk samples were tested with ER-TR chip with and without bacterial strains at varying concentration range 101-105 cells/mL. The sensor was integrated with in-house built printed circuit board (PCB) to transmit/receive electrical signals. The interaction of E. coli, S. mutans and B. subtilis cells with fibers of PNIPAm-GR resulted in a change of electrical resistance and the readout was monitored wirelessly in real-time using MATLAB algorithm. Finally, prepared ER-TR chip exhibited the reproducibility of 85-97% with shelf-life of up to four weeks after testing with lake water sample.

Fabrication of novel elastosomes for boosting the transdermal delivery of diacerein: statistical optimization, ex-vivo permeation, in-vivo skin deposition and pharmacokinetic assessment compared to oral formulation.

Diacerein (DCN) is a hydrophobic osteoarthritis (OA) drug with short half-life and low oral bioavailability. Furthermore, DCN oral administration is associated with diarrhea which represents obstacle against its oral use. Hence, this article aimed at developing elastosomes (edge activator (EA)-based vesicular nanocarriers) as a novel transdermal system for delivering DCN efficiently and avoiding its oral problems. For achieving this goal, elastosomes were prepared according to 41.21 full factorial design using different EAs in varying amounts. The prepared formulae were characterized regarding their entrapment efficiency percentage (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP) and deformability index (DI). Desirability function was employed using Design-Expert® software to select the optimal elastosomes (E1) which showed EE% of 96.25 ± 2.19%, PS of 506.35 ± 44.61 nm, PDI of 0.46 ± 0.09, ZP of -38.65 ± 0.91 mV, and DI of 12.74 ± 2.63 g. In addition, E1 was compared to DCN-loaded bilosomes and both vesicles exhibited superior skin permeation potential and retention capacity compared to drug suspension. In-vivo histopathological study was performed which ensured the safety of E1 for topical application. Furthermore, the pharmacokinetic study conducted in albino rabbits demonstrated that there was no significant difference in the rate and extent of DCN absorption from topically applied E1 compared to oral suspension. Multiple level C in-vitro in-vivo correlation showed good correlation between in-vitro release and in-vivo drug performance for E1 and DCN oral suspension. Overall, results confirmed the admirable potential of E1 to be utilized as novel carrier for transdermal delivery of DCN and bypassing its oral side effects.

Easy-to-perform and cost-effective fabrication of continuous-flow reactors and their application for nanomaterials synthesis.

The translation of continuous-flow microreactor technology to the industrial environment has been limited by cost and complexity of the fabrication procedures and the requirement for specialised infrastructure. In the present study, we have developed a significantly more cost-effective and easy-to-perform fabrication method for the generation of optically transparent, continuous-flow reactors. The method combines 3D printing of master moulds with sealing of the PDMS channels' replica using a pressure-sensitive adhesive tape. Morphological characterisation of the 3D printed moulds was performed and reactors were fabricated with an approximately square-shaped cross-section of 1 mm2. Notably, they were tested for operation over a wide range of volumetric flow rates, up to 20 ml/min. Moreover, the fabrication time (i.e., from design to the finished product) was <1 day, at an average material cost of ∼£5. The flow reactors have been applied to the production of both inorganic nanoparticles (silver nanospheres) and organic vesicular systems (liposomes), and their performance compared with reactors produced using more laborious fabrication methods. Numerical simulations were performed to characterise the transport of fluids and chemical species within the devices. The developed fabrication method is suitable for scaled-up fabrication of continuous-flow reactors, with potential for application in biotechnology and nanomedicine.

A facile photoelectrochemical sensor for high sensitive ROS and AA detection based on graphitic carbon nitride nanosheets.

Photoactive material is one of the main challenges for fabrication of sensitive and selective photoelectrochemical (PEC) sensor. Herein, a facile PEC sensor is constructed using graphitic carbon nitride nanosheets (g-C3N4 NSs) coated on the surface of ITO electrode, where electron donor properties of potassium ferrocyanide and ascorbic acid is utilized for the tracing of hydrogen peroxide (H2O2), hypochlorite (ClO-), and ascorbic acid (AA). Our designed PEC sensor exhibits a good linear range to H2O2 concentrations from 12.5 to 875 µM in pH = 7.4 and 2.5-400 µM in pH = 10, while that for AA is in the range from 0.25 to 100 µM in pH = 7.4, and with the same pH for ClO- concentrations in the range from 0.5 to 19 × 10-3% (V/V) in a bleach sample. Owing to the good responses towards the traces of H2O2, AA, and ClO-, our designed system may be used as H2O2, ClO-, and AA sensor for outdoor applications with high specificity, long-time stability and good reproducibility.

ZIF-67 derived porous Co3O4 hollow nanopolyhedron functionalized solution-gated graphene transistors for simultaneous detection of glucose and uric acid in tears.

Biomarkers in tears have attracted much attention in daily healthcare sensing and monitoring. Here, highly sensitive sensors for simultaneous detection of glucose and uric acid are successfully constructed based on solution-gated graphene transistors (SGGTs) with two separate Au gate electrodes, modified with GOx-CHIT and BSA-CHIT respectively. The sensitivity of the SGGT is dramatically improved by co-modifying the Au gate with ZIF-67 derived porous Co3O4 hollow nanopolyhedrons. The sensing mechanism for glucose sensor is attributed to the reaction of H2O2 generated by the oxidation of glucose near the gate, while the sensing mechanism for uric acid is due to the direct electro-oxidation of uric acid molecules on the gate. The optimized glucose and uric acid sensors show the detection limits both down to 100nM, far beyond the sensitivity required for non-invasive detection of glucose and uric acid in tears. The glucose and uric acid in real tear samples was quantitatively detected at 323.2 ± 16.1µM and 98.5 ± 16.3µM by using the functionalized SGGT device. Due to the low-cost, high-biocompatibility and easy-fabrication features of the ZIF-67 derived porous Co3O4 hollow nanopolyhedron, they provide excellent electrocatalytic nanomaterials for enhancing sensitivity of SGGTs for a broad range of disease-related biomarkers.

Sn Wears Super Skin: A New Design for Long Cycling Batteries.

Searching for new anode alternatives in lieu of graphite for lithium-ion batteries that can deliver better electrochemical performance to meet the emerging energy/power demands in electric vehicles becomes particularly challenging. We report a rationally designed hybrid composite as anode in LIB that exhibits a greatly improved gravimetric capacity of 727 mAh/g with a Coulombic efficiency of >99.8% after 3000 cycles at 1.0 C. A capacity of 662 mAh/g at a high rate of 5.0 C was obtained after impressively long 10 000 cycles. From the 50th to 10 000th cycle under 5.0 C, the capacity retention is >97% with a negligible decay of <0.00026% per cycle. The excellence in electrochemistry is attributed to the efficient stress relax, accommodable space, lack of agglomeration, and solid-electrolyte interphase consuming Li+ of a delicate composite configuration that is composed of a Sn kernel wearing adjustable TiO2 "skin".

Low-cost and facile synthesis of Ni(OH)2/ZnO nanostructures for high-sensitivity glucose detection.

An efficient electrode for non-enzymatic glucose detection is produced with low-cost techniques on a Cu wire. ZnO nanorods (NRs) were grown on a Cu wire by chemical bath deposition and were used as the substrate for pulsed electrodeposition of nanostructured Ni(OH)2 flakes. The effect of the electrodeposition potential on the final morphology and electrochemical behavior of the Ni(OH)2/ZnO/Cu structures is reported. ZnO NRs resulted to be well dressed by Ni(OH)2 flakes and were tested as glucose sensing electrodes in 0.1 M NaOH solution, showing high sensitivities (up to 3 mA mM-1 cm-2) and long-term stability. The presence of ZnO NRs was shown to improve the performance of the glucose sensor in terms of electrochemical stability over the time and sensitivity compared to Ni(OH)2/Cu sample. The reported data demonstrate a simple, versatile and low-cost fabrication approach for effective glucose sensing system within a urban mines framework.

In Vitro Assessment of Early Bacterial Activity on Micro/Nanostructured Ti6Al4V Surfaces.

It is imperative to understand and systematically compare the initial interactions between bacteria genre and surface properties. Thus, we fabricated a flat, anodized with 80 nm TiO2 nanotubes (NTs), and a rough Ti6Al4V surface. The materials were characterized using field-emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDX) and atomic force microscopy (AFM). We cultured in vitro Staphylococcus epidermidis (S. epidermidis) and Pseudomonas aeruginosa (P. aeruginosa) to evaluate the bacterial-surface behavior by FE-SEM and viability calculation. In addition, the initial effects of human osteoblasts were tested on the materials. Gram-negative bacteria showed promoted adherence and viability over the flat and rough surface, while NTs displayed opposite activity with altered morphology. Gram-positive bacteria illustrated similar cellular architecture over the surfaces but with promoted surface adhesion bonds on the flat alloy. Rough surfaces supported S. epidermidis viability, whilst NTs exhibited lower vitality. NTs advocated promoted better osteoblast organization with enhanced vitality. Gram-positive bacteria suggested preferred adhesion capability over flat and carbon-rich surfaces. Gram-negative bacteria were strongly disturbed by NTs but largely stimulated by flat and rough materials. Our work proposed that the chemical profile of the material surface and the bacterial cell wall characteristics might play an important role in the bacteria-surface interactions.

Optimization and continuous fabrication of moth-eye nanostructure array on flexible polyethylene terephthalate substrate towards broadband antireflection.

Reflection loss can cause harmful effects on the performance of optoelectronic devices, such as cell phones, notebooks, displays, solar cells, and light-emitting diode (LED) devices. In order to obtain broadband antireflection (AR) properties, many researchers have utilized surface texture techniques to produce AR subwavelength structures on the interfaces. Among the AR subwavelength structures, the moth-eye nanostructure is one of the most promising structures, with the potential for commercialization in the near future. In this research, to obtain broadband AR performance, the optimization of moth-eye nanostructures was first carried out using the finite difference time domain method within the spectral ranges of 400-800 nm, including the optimization of shape, height, pitch, and residual layer thickness. In addition, the continuous production of moth-eye nanostructure array upon a flexible polyethylene terephthalate substrate was demonstrated by using the roll-to-roll ultraviolet nanoimprint lithography (R2R UV-NIL) process and anodic aluminum oxide mold, which provided a solution for the cost-effective fabrication of moth-eye nanostructure array. The AR performance of moth-eye nanostructure array obtained by the R2R UV-NIL process was also investigated experimentally, and good consistence was shown with the simulated results. This research can provide a beneficial direction for the optimization and cost-effective production of the moth-eye nanostructure array.

Nitrogen-doped graphene-chitosan matrix based efficient chemiluminescent immunosensor for detection of chicken interleukin-4.

Chicken interleukin-4 (ChIL-4), which is released by activated type 2 helper (Th2) cells following their stimulation in vitro, is an important indicator for the study of cell-mediated immunity in chickens after infection or vaccination. In this work, the first ChIL-4 chemiluminescent (CL) immunosensor was developed via the immobilization of monoclonal ChIL-4 antibodies on a nitrogen-doped graphene (NG)-chitosan nanocomposite matrix. NG nanosheets were used for the first time in the CL immunoassay to provide a biocompatible microenvironment for the immobilized capture antibody. The ChIL-4 immunosensor was characterized systematically. The proposed immunosensor displayed a wide linear range from 0.05 to 70ngmL-1 and a low detection limit of 0.02ngmL-1 at a signal-to-noise ratio of 3. Compared to traditional assay methods, this system was more flexible, simple, rapid, and sensitive. Moreover, this CL immunoassay system had an excellent detection and fabrication reproducibility, a high specificity, an acceptable accuracy, and a high stability. This work enables the specific detection of ChIL-4 and the further study of its role in the immune responses of poultry.

A cost-effective method to prepare curcumin nanosuspensions with enhanced oral bioavailability.

BACKGROUND: Nanosuspension is one of the most promising strategies to improve the oral bioavailability of insoluble drugs. The existing techniques applied to produce nanosuspensions are classified as "bottom-up" or "top-down" methods, or a combination of both. Curcumin (CUR), a Biopharmaceutics Classification System (BCS) class IV substance, is a promising drug candidate in view of its good bioactivity, but its use is limited due to its poor solubility and permeability. In the present study, CUR nanosuspensions were developed to enhance CUR oral bioavailability using a cost-effective method different from conventional techniques. RESULTS: The physicochemical properties of CUR nanosuspensions were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The crystalline state of CUR in different nanosuspensions analyzed using differential scanning calorimeter (DSC) and X-ray diffraction analysis (PXRD) confirmed its amorphous state. In vitro dissolution degree of the prepared CUR nanosuspensions using TPGS or Brij78 as stabilizer was greatly increased. Pharmacokinetic studies demonstrated that the oral bioavailability of CUR was increased 3.18 and 3.7 times after administration of CUR/TPGS nanosuspensions or CUR/Brij78 nanosuspensions, when compared with the administration of CUR suspension. CONCLUSIONS: CUR nanosuspensions produced by our cost-effective method could improve its oral bioavailability. In addition, the low-cost and time-saving method reported here is highly suitable for a fast and inexpensive preparation.

Fabrication and response of alpha-hydroxybutyrate sensors for rapid assessment of cardiometabolic disease risk.

Early diagnosis and treatment can prevent or delay progression of early-stage type 2 diabetes and prediabetes. Unfortunately, tests such as hemoglobin A1c (HbA1c)/fasting plasma glucose (FPG) alone fail to diagnose or miscategorize up to 40% of individuals with impaired glucose tolerance (IGT) or frank diabetes based on the rarely utilized oral glucose tolerance test (OGTT). The serum metabolite alpha-hydroxybutyrate (AHB) is increasingly recognized as a reliable IGT and diabetes predictor, and can be measured using liquid chromatography-tandem mass spectrometry. However, to address AHB adoption as a population screening tool, the reliable and low-cost measurement techniques are proposed. A periodate based oxidation was performed for an AHB-based buffer, and both nitroprusside and Raman tests confirmed the formation of a slow-oxidation product. Electrochemical tests of AHB-based buffers using electrodes such as Au-honeycomb, thiol self-assembled monolayers coated Au, 2D material (black-P) coated FTO, (3-aminophenyl) triethoxysilane modified TiO2, were performed. Many of these electrodes exhibited a systematic response when AHB concentration was varied from ~1.0-12.0µg/ml. A colorimetric assay containing a vicinal-diol recognition moiety, additives, and a photoinitiator, exhibited a different color for AHB based buffer. Benesi-Hildebrand analysis indicated the association behavior of boronic acid and AHB. These methods have a potential to be used for rapid point-of-care measurements of AHB that could enhance population-wide diabetes and prediabetes screening strategies.