Search results for: nano-scale microenvironment

Authors: Aloke Bapli, Debabrata Seth

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Graphene oxide (GO) is the two-dimensional (2D) nanoscale allotrope of carbon having several physiochemical properties such as high mechanical strength, high surface area, strong thermal and electrical conductivity makes it an important candidate in various modern applications such as drug delivery, supercapacitors, sensors etc. GO has been used in the photothermal treatment of cancers and Alzheimer’s disease etc. The main idea to choose GO in our work is that it is a surface active molecule, it has a large number of hydrophilic functional groups such as carboxylic acid, hydroxyl, epoxide on its surface and in basal plane. So it can easily interact with organic fluorophores through hydrogen bonding or any other kind of interaction and easily modulate the photophysics of the probe molecules. We have used different spectroscopic techniques for our work. The Ground-state absorption spectra and steady-state fluorescence emission spectra were measured by using UV-Vis spectrophotometer from Shimadzu (model-UV-2550) and spectrofluorometer from Horiba Jobin Yvon (model-Fluoromax 4P) respectively. All the fluorescence lifetime and anisotropy decays were collected by using time-correlated single photon counting (TCSPC) setup from Edinburgh instrument (model: LifeSpec-II, U.K.). Herein, we described the photophysics of a hydrophilic molecule 7-(n,n׀-diethylamino) coumarin-3-carboxylic acid (7-DCCA) in the reverse micelles containing GO. It was observed that photophysics of dye is modulated in the presence of GO compared to photophysics of dye in the absence of GO inside the reverse micelles. Here we have reported the solvent relaxation and rotational relaxation time in GO containing reverse micelle and compare our work with normal reverse micelle system by using 7-DCCA molecule. Normal reverse micelle means reverse micelle in the absence of GO. The absorption maxima of 7-DCCA were blue shifted and emission maxima were red shifted in GO containing reverse micelle compared to normal reverse micelle. The rotational relaxation time in GO containing reverse micelle is always faster compare to normal reverse micelle. Solvent relaxation time, at lower w₀ values, is always slower in GO containing reverse micelle compare to normal reverse micelle and at higher w₀ solvent relaxation time of GO containing reverse micelle becomes almost equal to normal reverse micelle. Here emission maximum of 7-DCCA exhibit bathochromic shift in GO containing reverse micelles compared to that in normal reverse micelles because in presence of GO the polarity of the system increases, as polarity increases the emission maxima was red shifted an average decay time of GO containing reverse micelle is less than that of the normal reverse micelle. In GO containing reverse micelle quantum yield, decay time, rotational relaxation time, solvent relaxation time at λₑₓ=375 nm is always higher than λₑₓ=405 nm, shows the excitation wavelength dependent photophysics of 7-DCCA in GO containing reverse micelles.

Keywords: photophysics, reverse micelle, rotational relaxation, solvent relaxation

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Authors: Archana Sharma, Vijayashree Nayak, Ashok Kumar

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Three-dimensional matrices were fabricated from blend of natural-natural polymers like carrageenan-gelatin and synthetic -natural polymers such as PEG- gelatin (PEG of different molecular weights (2,000 and 6,000) using two different crosslinkers; glutaraldehyde and EDC-NHS by cryogelation technique. Blends represented a feasible approach to design 3-D scaffolds with controllable mechanical, physical and biochemical properties without compromising biocompatibility and biodegradability. These matrices possessed interconnected porous structure, good mechanical strength, biodegradable nature, constant swelling kinetics, ability to withstand high temperature and visco-elastic behavior. Hemocompatibility of cryogel matrices was determined by coagulation assays and hemolytic activity assay which demonstrated that these cryogels have negligible effects on coagulation time and have excellent blood compatibility. In vitro biocompatibility (cell-matrix interaction) inferred good cell adhesion, proliferation, and secretion of ECM on matrices. These matrices provide a microenvironment for the growth, proliferation, differentiation and secretion of ECM of different cell types such as IMR-32, C2C12, Cos-7, rat bone marrow derived MSCs and human bone marrow MSCs. Hoechst 33342 and PI staining also confirmed that the cells were uniformly distributed, adhered and proliferated properly on the cryogel matrix. An ideal scaffold used for tissue engineering application should allow the cells to adhere, proliferate and maintain their functionality. Neurotransmitter analysis has been done which indicated that IMR-32 cells adhered, proliferated and secreted neurotransmitters when they interacted with these matrices which showed restoration of their functionality. The cell-matrix interaction up to molecular level was also evaluated so to check genotoxicity and protein expression profile which indicated that these cryogel matrices are non-genotoxic and maintained biofunctionality of cells growing on these matrices. All these cryogels, when implanted subcutaneously in balb/c mice, showed no adverse systemic or local toxicity effects at implantation site. There was no significant increase in inflammatory cell count has otherwise been observed after scaffold implantation. These cryogels are supermacroporous and this porous structure allows cell infiltration and proliferation of host cells. This showed the integration and presence of infiltrated cells into the cryogel implants. Histological analysis confirmed that the implanted cryogels do not have any adverse effect in spite of host immune system recognition at the site of implantation, on its surrounding tissues and other vital host organs. In vivo biocompatibility study after in vitro biocompatibility analysis has also concluded that these synthesized cryogels act as important biological substitutes, more adaptable and appropriate for transplantation. Thus, these cryogels showed their potential for soft tissue engineering applications.

Keywords: cryogelation, hemocompatibility, in vitro biocompatibility, in vivo biocompatibility, soft tissue engineering applications

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Authors: Maciej Szelag

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The discovery of the carbon nanotubes (CNT), has led to a breakthrough in the material engineering. The CNT is characterized by very large surface area, very high Young's modulus (about 2 TPa), unmatched durability, high tensile strength (about 50 GPa) and bending strength. Their diameter usually oscillates in the range from 1 to 100 nm, and the length from 10 nm to 10-2 m. The relatively new approach is the CNT’s application in the concrete technology. The biggest problem in the use of the CNT to cement composites is their uneven dispersion and low adhesion to the cement paste. Putting the nanotubes alone into the cement matrix does not produce any effect because they tend to agglomerate, due to their large surface area. Most often, the CNT is used as an aqueous suspension in the presence of a surfactant that has previously been sonicated. The paper presents the results of investigations of the basic physical properties (apparent density, shrinkage) and mechanical properties (compression and tensile strength) of cement paste with the addition of the multiwall carbon nanotubes (MWCNT). The studies were carried out on four series of specimens (made of two different Portland Cement). Within each series, samples were made with three w/c ratios – 0.4, 0.5, 0.6 (water/cement). Two series were an unmodified cement matrix. In the remaining two series, the MWCNT was added in amount of 0.1% by cement’s weight. The MWCNT was used as an aqueous dispersion in the presence of a surfactant – SDS – sodium dodecyl sulfate (C₁₂H₂₅OSO₂ONa). So prepared aqueous solution was sonicated for 30 minutes. Then the MWCNT aqueous dispersion and cement were mixed using a mechanical stirrer. The parameters were tested after 28 days of maturation. Additionally, the change of these parameters was determined after samples temperature loading at 250°C for 4 hours (thermal shock). Measurement of the apparent density indicated that cement paste with the MWCNT addition was about 30% lighter than conventional cement matrix. This is due to the fact that the use of the MWCNT water dispersion in the presence of surfactant in the form of SDS resulted in the formation of air pores, which were trapped in the volume of the material. SDS as an anionic surfactant exhibits characteristics specific to blowing agents – gaseous and foaming substances. Because of the increased porosity of the cement paste with the MWCNT, they have obtained lower compressive and tensile strengths compared to the cement paste without additive. It has been observed, however, that the smallest decreases in the compressive and tensile strength after exposure to the elevated temperature achieved samples with the MWCNT. The MWCNT (well dispersed in the cement matrix) can form bridges between hydrates in a nanoscale of the material’s structure. Thus, this may result in an increase in the coherent cohesion of the cement material subjected to a thermal shock. The obtained material could be used for the production of an aerated concrete or using lightweight aggregates for the production of a lightweight concrete.

Keywords: cement paste, elevated temperature, mechanical parameters, multiwall carbon nanotubes, physical parameters, SDS

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Authors: Amelia J. McFarland, Andrew K. Davey, Shailendra Anoopkumar-Dukie

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Microglia are the resident macrophage population of the central nervous system (CNS), contributing to both innate and adaptive immune response, and brain homeostasis. Activation of microglia occurs in response to a multitude of pathogenic stimuli in their microenvironment; this induces morphological and functional changes, resulting in a state of acute neuroinflammation which facilitates injury resolution. Adequate microglial function is essential for the health of the neuroparenchyma, with microglial dysfunction implicated in numerous CNS pathologies. Given the critical role that these macrophage-derived cells play in CNS homeostasis, there is a high demand for microglial models suitable for use in neuroscience research. The isolation of primary human microglia, however, is both difficult and costly, with microglial activation an unwanted but inevitable result of the extraction process. Consequently, there is a need for the development of alternative experimental models which exhibit morphological, biochemical and functional characteristics of human microglia without the difficulties associated with primary cell lines. In this study, our aim was to evaluate whether THP-1 human peripheral blood monocytes would display microglial-like qualities following an induced differentiation, and, therefore, be suitable for use as surrogate microglia. To achieve this aim, THP-1 human peripheral blood monocytes from acute monocytic leukaemia were differentiated with a range of phorbol 12-myristate 13-acetate (PMA) concentrations (50-200 nM) using two different protocols: a 5-day continuous PMA exposure or a 3-day continuous PMA exposure followed by a 5-day rest in normal media. In each protocol and at each PMA concentration, microglial-like cell morphology was assessed through crystal violet staining and the presence of CD-14 microglial / macrophage cell surface marker. Lipopolysaccharide (LPS) from Escherichia coli (055: B5) was then added at a range of concentrations from 0-10 mcg/mL to activate the PMA-differentiated THP-1 cells. Functional microglial-like behavior was evaluated by quantifying the release of prostaglandin (PG)-E2 and pro-inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α using mediator-specific ELISAs. Furthermore, production of global reactive oxygen species (ROS) and nitric oxide (NO) were determined fluorometrically using dichlorodihydrofluorescein diacetate (DCFH-DA) and diaminofluorescein diacetate (DAF-2-DA) respectively. Following PMA-treatment, it was observed both differentiation protocols resulted in cells displaying distinct microglial morphology from 10 nM PMA. Activation of differentiated cells using LPS significantly augmented IL-1β, TNF-α and PGE2 release at all LPS concentrations under both differentiation protocols. Similarly, a significant increase in DCFH-DA and DAF-2-DA fluorescence was observed, indicative of increases in ROS and NO production. For all endpoints, the 5-day continuous PMA treatment protocol yielded significantly higher mediator levels than the 3-day treatment and 5-day rest protocol. Our data, therefore, suggests that the differentiation of THP-1 human monocyte cells with PMA yields a homogenous microglial-like population which, following stimulation with LPS, undergo activation to release a range of pro-inflammatory mediators associated with microglial activation. Thus, the use of PMA-differentiated THP-1 cells represents a suitable microglial model for in vitro research.

Keywords: differentiation, lipopolysaccharide, microglia, monocyte, neuroscience, THP-1

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Authors: Ingrid Snustad, Asmund Ervik, Anders Austegard, Amy Brunsvold, Jianying He, Zhiliang Zhang

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CO₂ capture, transport and storage (CCS) is essential to mitigate global anthropogenic CO₂ emissions. To make CCS a widely implemented technology in, e.g. the power sector, the reduction of costs is crucial. For a large cost reduction, every part of the CCS chain must contribute. By increasing the heat transfer efficiency during liquefaction of CO₂, which is a necessary step, e.g. ship transportation, the costs associated with the process are reduced. Heat transfer rates during dropwise condensation are up to one order of magnitude higher than during filmwise condensation. Dropwise condensation usually occurs on a non-wetting surface (Superlyophobic surface). The vapour condenses in discrete droplets, and the non-wetting nature of the surface reduces the adhesion forces and results in shedding of condensed droplets. This, again, results in fresh nucleation sites for further droplet condensation, effectively increasing the liquefaction efficiency. In addition, the droplets in themselves have a smaller heat transfer resistance than a liquid film, resulting in increased heat transfer rates from vapour to solid. Surface tension is a crucial parameter for dropwise condensation, due to its impact on the solid-liquid contact angle. A low surface tension usually results in a low contact angle, and again to spreading of the condensed liquid on the surface. CO₂ has very low surface tension compared to water. However, at relevant temperatures and pressures for CO₂ condensation, the surface tension is comparable to organic compounds such as pentane, a dropwise condensation of CO₂ is a completely new field of research. Therefore, knowledge of several important parameters such as contact angle and drop size distribution must be gained in order to understand the nature of the condensation. A new setup has been built to measure these relevant parameters. The main parts of the experimental setup is a pressure chamber in which the condensation occurs, and a high- speed camera. The process of CO₂ condensation is visually monitored, and one can determine the contact angle, contact angle hysteresis and hence, the surface adhesion of the liquid. CO₂ condensation on different surfaces can be analysed, e.g. copper, aluminium and stainless steel. The experimental setup is built for accurate measurements of the temperature difference between the surface and the condensing vapour and accurate pressure measurements in the vapour. The temperature will be measured directly underneath the condensing surface. The next step of the project will be to fabricate nanostructured surfaces for inducing superlyophobicity. Roughness is a key feature to achieve contact angles above 150° (limit for superlyophobicity) and controlled, and periodical roughness on the nanoscale is beneficial. Surfaces that are non- wetting towards organic non-polar liquids are candidates surface structures for dropwise condensation of CO₂.

Keywords: CCS, dropwise condensation, low surface tension liquid, superlyophobic surfaces

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Authors: Esther Friedlander, Philip Friedlander

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The use of immunotherapy that inhibits programmed death-1 (PD-1) or its ligand PD-L1 confers survival benefits in patients with non-small cell lung cancer (NSCLC). However, approximately 45% of patients experience primary treatment resistance, necessitating the development of strategies to improve efficacy. While the renin-angiotensin system (RAS) has systemic hemodynamic effects, tissue-specific regulation exists along with modulation of immune activity in part through regulation of myeloid cell activity, leading to the hypothesis that RAS inhibition may improve anti-PD-1/L-1 efficacy. A retrospective analysis was conducted that included 173 advanced solid tumor cancer patients treated at Valley Hospital, a community Hospital in New Jersey, USA, who were treated with a PD-1/L-1 inhibitor in a defined time period showing a statistically significant relationship between RAS pathway inhibition (RASi through concomitant treatment with an ACE inhibitor or angiotensin receptor blocker) and positive efficacy to the immunotherapy that was independent of age, gender and cancer type. Subset analysis revealed strong numerical benefit for efficacy in both patients with squamous and nonsquamous NSCLC as determined by documented clinician assessment of efficacy and by duration of therapy. A PUBMED literature search was now conducted to identify studies assessing the effect of RAS pathway inhibition on anti-PD-1/L1 efficacy in advanced solid tumor patients and compare these findings to those seen in the Valley Hospital retrospective study with a focus on NSCLC specifically. A total of 11 articles were identified assessing the effects of RAS pathway inhibition on the efficacy of checkpoint inhibitor immunotherapy in advanced cancer patients. Of the 11 studies, 10 assessed the effect on survival of RASi in the context of treatment with anti-PD-1/PD-L1, while one assessed the effect on CTLA-4 inhibition. Eight of the studies included patients with NSCLC, while the remaining 2 were specific to genitourinary malignancies. Of the 8 studies, two were specific to NSCLC patients, with the remaining 6 studies including a range of cancer types, of which NSCLC was one. Of these 6 studies, only 2 reported specific survival data for the NSCLC subpopulation. Patient characteristics, multivariate analysis data and efficacy data seen in the 2 NSLCLC specific studies and in the 2 basket studies, which provided data on the NSCLC subpopulation, were compared to that seen in the Valley Hospital retrospective study supporting a broader effect of RASi on anti-PD-1/L1 efficacy in advanced NSLCLC with the majority of studies showing statistically significant benefit or strong statistical trends but with one study demonstrating worsened outcomes. This comparison of studies extends published findings to the community hospital setting and supports prospective assessment through randomized clinical trials of efficacy in NSCLC patients with pharmacodynamic components to determine the effect on immune cell activity in tumors and on the composition of the tumor microenvironment.

Keywords: immunotherapy, cancer, angiotensin, efficacy, PD-1, lung cancer, NSCLC

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Authors: Kai-Cheng Yang, Yen-Ling Chen, Er-Chieh Cho, Kuen-Chan Lee

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Titanium dioxide nanomaterials offer superior protection for human skin against the full spectrum of ultraviolet light. However, some literature reviews indicated that it might be associated with adverse effects such as cytotoxicity or reactive oxygen species (ROS) due to their nanoscale. The surface of fullerene is covered with π electrons constituting aromatic structures, which can effectively scavenge large amount of radicals. Unfortunately, fullerenes are poor solubility in water, severe aggregation, and toxicity in biological applications when dispersed in solvent have imposed the limitations to the use of fullerenes. Carboxyfullerene acts as the scavenger of radicals for several years. Some reports indicate that carboxyfullerene not only decrease the concentration of free radicals in ambience but also prevent cells from reducing the number or apoptosis under UV irradiation. The aim of this study is to decorate fullerene –C70-carboxylic acid (C70-COOH) on the surface of titanium dioxide nanoparticles (P25) for the purpose of scavenging ROS during the irradiation. The modified material is prepared through the esterification of C70-COOH with P25 (P25/C70-COOH). The binding edge and structure are studied by using Transmission electron microscope (TEM) and Fourier transform infrared (FTIR). The diameter of P25 is about 30 nm and C70-COOH is found to be conjugated on the edge of P25 in aggregation morphology with the size of ca. 100 nm. In the next step, the FTIR was used to confirm the binding structure between P25 and C70-COOH. There are two new peaks are shown at 1427 and 1720 cm-1 for P25/C70-COOH, resulting from the C–C stretch and C=O stretch formed during esterification with dilute sulfuric acid. The IR results further confirm the chemically bonded interaction between C70-COOH and P25. In order to provide the evidence of scavenging radical ability of P25/C70-COOH, we chose pyridoxine (Vit.B6) and terephthalic acid (TA) to react with singlet oxygen and hydroxyl radicals. We utilized these chemicals to observe the radicals scavenging statement via detecting the intensity of ultraviolet adsorption or fluorescence emission. The UV spectra are measured by using different concentration of C70-COOH modified P25 with 1mM pyridoxine under UV irradiation for various duration times. The results revealed that the concentration of pyridoxine was increased when cooperating with P25/C70-COOH after three hours as compared with control (only P25). It indicates fewer radicals could be reacted with pyridoxine because of the absorption via P25/C70-COOH. The fluorescence spectra are observed by measuring P25/C70-COOH with 1mM terephthalic acid under UV irradiation for various duration times. The fluorescence intensity of TAOH was decreased in ten minutes when cooperating with P25/C70-COOH. Here, it was found that the fluorescence intensity was increased after thirty minutes, which could be attributed to the saturation of C70-COOH in the absorption of radicals. However, the results showed that the modified P25/C70-COOH could reduce the radicals in the environment. Therefore, we expect that P25/C70-COOH is a potential materials in using for antioxidant.

Keywords: titanium dioxide, fullerene, radical scavenging activity, antioxidant

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Authors: Jana Andzane, Gunta Kunakova, Margarita Baitimirova, Mikelis Marnauza, Floriana Lombardi, Donats Erts

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Bismuth selenide (Bi₂Se₃) is known as a narrow band gap semiconductor with pronounced thermoelectric (TE) and topological insulator (TI) properties. Unique TI properties offer exciting possibilities for fundamental research as observing the exciton condensate and Majorana fermions, as well as practical application in spintronic and quantum information. In turn, TE properties of this material can be applied for wide range of thermoelectric applications, as well as for broadband photodetectors and near-infrared sensors. Nanostructuring of this material results in improvement of TI properties due to suppression of the bulk conductivity, and enhancement of TE properties because of increased phonon scattering at the nanoscale grains and interfaces. Regarding TE properties, crystallographic growth direction, as well as orientation of the nanostructures relative to the growth substrate, play significant role in improvement of TE performance of nanostructured material. For instance, Bi₂Se₃ layers consisting of randomly oriented nanostructures and/or of combination of them with planar nanostructures show significantly enhanced in comparison with bulk and only planar Bi₂Se₃ nanostructures TE properties. In this work, a catalyst-free vapour-solid deposition technique was applied for controlled obtaining of different types of Bi₂Se₃ nanostructures and continuous nanostructured layers for targeted applications. For example, separated Bi₂Se₃ nanoplates, nanobelts and nanowires can be used for investigations of TI properties; consisting from merged planar and/or randomly oriented nanostructures Bi₂Se₃ layers are useful for applications in heat-to-power conversion devices and infrared detectors. The vapour-solid deposition was carried out using quartz tube furnace (MTI Corp), equipped with an inert gas supply and pressure/temperature control system. Bi₂Se₃ nanostructures/nanostructured layers of desired type were obtained by adjustment of synthesis parameters (process temperature, deposition time, pressure, carrier gas flow) and selection of deposition substrate (glass, quartz, mica, indium-tin-oxide, graphene and carbon nanotubes). Morphology, structure and composition of obtained Bi₂Se₃ nanostructures and nanostructured layers were inspected using SEM, AFM, EDX and HRTEM techniques, as well as home-build experimental setup for thermoelectric measurements. It was found that introducing of temporary carrier gas flow into the process tube during the synthesis and deposition substrate choice significantly influence nanostructures formation mechanism. Electrical, thermoelectric, and topological insulator properties of different types of deposited Bi₂Se₃ nanostructures and nanostructured coatings are characterized as a function of thickness and discussed.

Keywords: bismuth seleinde, nanostructures, topological insulator, vapour-solid deposition

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Authors: Sahar Nasr, Lin Li, Edwin Wang

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Bladder cancer (BLCA) is known as the 13th cause of death among cancer patients worldwide, and ~575,000 new BLCA cases are diagnosed each year. Urothelial carcinoma (UC) is the most prevalent subtype among BLCA patients, which can be categorized into muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Currently, various therapeutic options are available for UC patients, including (1) transurethral resection followed by intravesical instillation of chemotherapeutics or Bacillus Calmette-Guérin for NMIBC patients, (2) neoadjuvant platinum-based chemotherapy (NAC) plus radical cystectomy is the standard of care for localized MIBC patients, and (3) systematic chemotherapy for metastatic UC. However, conventional treatments may lead to several challenges for treating patients. As an illustration, some patients may suffer from recurrence of the disease after the first line of treatment. Recently, immune checkpoint therapy (ICT) has been introduced as an alternative treatment strategy for the first or second line of treatment in advanced or metastatic BLCA patients. Although ICT showed lucrative results for a fraction of BLCA patients, ~80% of patients were not responsive to it. Therefore, novel treatment methods are required to augment the ICI response rate within BLCA patients. It has been shown that the infiltration of T-cells into the tumor microenvironment (TME) is positively correlated with the response to ICT within cancerous patients. Therefore, the goal of this study is to enhance the infiltration of cytotoxic T-cells into TME through the identification of target genes within the tumor that are responsible for the non-T-cell inflamed TME and their inhibition. BLCA bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) and immune score for TCGA samples were used to determine the Pearson correlation score between the expression of different genes and immune score for each sample. The genes with strong negative correlations were selected (r < -0.2). Thereafter, the correlation between the expression of each gene and survival in BLCA patients was calculated using the TCGA data and Cox regression method. The genes that are common in both selected gene lists were chosen for further analysis. Afterward, BLCA bulk and single-cell RNA-sequencing data were ranked based on the expression of each selected gene and the top and bottom 25% samples were used for pathway enrichment analysis. If the pathways related to the T-cell infiltration (e.g., antigen presentation, interferon, or chemokine pathways) were enriched within the low-expression group, the gene was included for downstream analysis. Finally, the selected genes will be used to calculate the correlation between their expression and the infiltration rate of the activated CD+8 T-cells, natural killer cells and the activated dendric cells. A list of potential target genes has been identified and ranked based on the above-mentioned analysis and criteria. SUN-1 got the highest score within the gene list and other identified genes in the literature as benchmarks. In conclusion, inhibition of SUN1 may increase the tumor-infiltrating lymphocytes and the efficacy of ICI in BLCA patients. BLCA tumor cells with and without SUN-1 CRISPR/Cas9 knockout will be injected into the syngeneic mouse model to validate the predicted SUN-1 effect on increasing tumor-infiltrating lymphocytes.

Keywords: data analysis, gene expression analysis, gene identification, immunoinformatic, functional genomics, transcriptomics

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Authors: J. J. Rickard, A. Belli, P. Goldberg Oppenheimer

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Medical diagnostics, environmental monitoring, homeland security and forensics increasingly demand specific and field-deployable analytical technologies for quick point-of-care diagnostics. Although technological advancements have made optical methods well-suited for miniaturization, a highly-sensitive detection technique for minute sample volumes is required. Raman spectroscopy is a well-known analytical tool, but has very weak signals and hence is unsuitable for trace level analysis. Enhancement via localized optical fields (surface plasmons resonances) on nanoscale metallic materials generates huge signals in surface-enhanced Raman scattering (SERS), enabling single molecule detection. This enhancement can be tuned by manipulation of the surface roughness and architecture at the sub-micron level. Nevertheless, the development and application of SERS has been inhibited by the irreproducibility and complexity of fabrication routes. The ability to generate straightforward, cost-effective, multiplex-able and addressable SERS substrates with high enhancements is of profound interest for SERS-based sensing devices. While most SERS substrates are manufactured by conventional lithographic methods, the development of a cost-effective approach to create nanostructured surfaces is a much sought-after goal in the SERS community. Here, a method is established to create controlled, self-organized, hierarchical nanostructures using electrohydrodynamic (HEHD) instabilities. The created structures are readily fine-tuned, which is an important requirement for optimizing SERS to obtain the highest enhancements. HEHD pattern formation enables the fabrication of multiscale 3D structured arrays as SERS-active platforms. Importantly, each of the HEHD-patterned individual structural units yield a considerable SERS enhancement. This enables each single unit to function as an isolated sensor. Each of the formed structures can be effectively tuned and tailored to provide high SERS enhancement, while arising from different HEHD morphologies. The HEHD fabrication of sub-micrometer architectures is straightforward and robust, providing an elegant route for high-throughput biological and chemical sensing. The superior detection properties and the ability to fabricate SERS substrates on the miniaturized scale, will facilitate the development of advanced and novel opto-fluidic devices, such as portable detection systems, and will offer numerous applications in biomedical diagnostics, forensics, ecological warfare and homeland security.

Keywords: hierarchical electrohydrodynamic patterning, medical diagnostics, point-of care devices, SERS

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Authors: Farrah Putri Salmanida, Mei-Li Wu, Rika Wahyuningtyas, Wen-Bin Chung, Hso-Chi Chaung, Ko-Tung Chang

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Within the field of immunotherapy, oncolytic virotherapy (OVT) employs dual approaches that directly eliminate tumor cells while preserving healthy ones and indirectly reprogram the tumor microenvironment (TME) to elicit antitumor responses. Within the TME, tumor associated macrophages (TAMs) manifest characteristics akin to those of anti-inflammatory M2 macrophages, thus earning the designation of M2-like TAMs. In prior research, two antigens denoted as A1 (g6Ld10T) and A3 (ORF6L5), derived from a complete sequence of ORF5 with partial sequence of ORF6 in Porcine Reproductive and Respiratory Syndrome Virus Genotype 2 (PRRSV-2), demonstrated the capacity to repolarize M2-type porcine alveolar macrophages (PAMs) into M1 phenotypes. In this study, we sought for utilizing OVT strategies by introducing A1 or A3 on TAMs to endow them with the anti-tumor traits of M1 macrophages while retaining their capacity to target cancer cells. Upon exposing human THP-1-derived M2 macrophages to a cross-species test with 2 µg/ml of either A1 or A3 for 24 hours, real time PCR revealed that A3, but not A1, treated cells exhibited upregulated gene expressions of M1 markers (CCR7, IL-1ß, CCL2, Cox2, CD80). These cells reacted to virus-derived antigen, as evidenced by increased expression of pattern-recognition receptors TLR3, TLR7, and TLR9, subsequently providing feedback in the form of type I interferon responses like IFNAR1, IFN-ß, IRF3, IRF7, OAS1, Mx1, and ISG15. Through an MTT assay, only after 15 µg/ml of A3 treatment could the cell viability decrease, with a predicted IC50 of 16.96 µg/ml. Interestingly, A3 caused dose-dependent toxicity to a rat C6 glial cancer cell line even at doses as low as 2.5 µg/ml and reached its IC50 at 9.419 µg/ml. Using Annexin V/7AAD staining and PCR test, we deduced that a significant proportion of C6 cells were undergoing the early apoptosis phase predominantly through the intrinsic apoptosis cascade involving Bcl-2 family proteins. Following this stage, we conducted a test on A3’s repolarization ability, which revealed a significant rise in M1 gene expression markers, such as TNF, CD80, and IL-1ß, in M2-like TAMs generated in vitro from murine RAW264.7 macrophages grown with conditioned medium of 4T1 breast cancer cells. This was corroborated by the results of transcriptome analysis, which revealed that the primary subset among the top 10 to top 30 significantly upregulated differentially expressed genes (DEGs) dominantly consisted of M1 macrophages profiles, including Ccl3, Ccl4, Csf3, TNF, Bcl6b, Stc1, and Dusp2. Our findings unveiled the remarkable potential of the PRRSV-derived antigen A3 to repolarize macrophages while also being capable of selectively inducing apoptosis in cancerous cells. While further in vivo study is needed for A3, it holds promise as an adjuvant by its dual effects in cancer therapy modalities.

Keywords: cancer cell apoptosis, interferon responses, macrophage repolarization, recombinant protein

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Authors: S.V. Kleyn, S.Yu. Zagorodnov, А.А. Kokoulina

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Technogenic emissions of the mining and processing complex are characterized by a high content of chemical components and solid dust particles. However, each industrial enterprise and the surrounding area have features that require refinement and parameterization. Numerous studies have shown the negative impact of fine dust PM10 and PM2.5 on the health, as well as the possibility of toxic components absorption, including heavy metals by dust particles. The target of the study was the quantitative assessment of the fractional and particle size composition of ambient air dust in the area of impact by primary magnesium production complex. Also, we tried to describe the morphology features of dust particles. Study methods. To identify the dust emission sources, the analysis of the production process has been carried out. The particulate composition of the emissions was measured using laser particle analyzer Microtrac S3500 (covered range of particle size is 20 nm to 2000 km). Particle morphology and the component composition were established by electron microscopy by scanning microscope of high resolution (magnification rate - 5 to 300 000 times) with X-ray fluorescence device S3400N ‘HITACHI’. The chemical composition was identified by X-ray analysis of the samples using an X-ray diffractometer XRD-700 ‘Shimadzu’. Determination of the dust pollution level was carried out using model calculations of emissions in the atmosphere dispersion. The calculations were verified by instrumental studies. Results of the study. The results demonstrated that the dust emissions of different technical processes are heterogeneous and fractional structure is complicated. The percentage of particle sizes up to 2.5 micrometres inclusive was ranged from 0.00 to 56.70%; particle sizes less than 10 microns inclusive – 0.00 - 85.60%; particle sizes greater than 10 microns - 14.40% -100.00%. During microscopy, the presence of nanoscale size particles has been detected. Studied dust particles are round, irregular, cubic and integral shapes. The composition of the dust includes magnesium, sodium, potassium, calcium, iron, chlorine. On the base of obtained results, it was performed the model calculations of dust emissions dispersion and establishment of the areas of fine dust РМ 10 and РМ 2.5 distribution. It was found that the dust emissions of fine powder fractions PM10 and PM2.5 are dispersed over large distances and beyond the border of the industrial site of the enterprise. The population living near the enterprise is exposed to the risk of diseases associated with dust exposure. Data are transferred to the economic entity to make decisions on the measures to minimize the risks. Exposure and risks indicators on the health are used to provide named patient health and preventive care to the citizens living in the area of negative impact of the facility.

Keywords: dust emissions, еxposure assessment, PM 10, PM 2.5

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Authors: A. V. Samokhin, A. A. Fadeev, M. A. Sinaiskii, N. V. Alekseev, A. V. Kolesnikov

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Composite materials where metal matrix is reinforced by ceramic or metal particles are of great interest for use in the manufacturing of electrical contacts. Significant improvement of the composite physical and mechanical properties as well as increase of the performance parameters of composite-based products can be achieved if the nanoscale structure in the composite materials is obtained by using nanosized powders as starting components. The results of nanosized composite powders synthesis (Ag-SnO2, W-Cu and Cu-C) in the DC thermal plasma flows are presented in this paper. The investigations included the following processes: - Recondensation of micron powder mixture Ag + SnO2 in a nitrogen plasma; - The reduction of the oxide powders mixture (WO3 + CuO) in a hydrogen-nitrogen plasma; - Decomposition of the copper formate and copper acetate powders in nitrogen plasma. The calculations of equilibrium compositions of multicomponent systems Ag-Sn-O-N, W-Cu-O-H-N and Cu-O-C-H-N in the temperature range of 400-5000 K were carried to estimate basic process characteristics. Experimental studies of the processes were performed using a plasma reactor with a confined jet flow. The plasma jet net power was in the range of 2 - 13 kW, and the feedstock flow rate was up to 0.35 kg/h. The obtained powders were characterized by TEM, HR-TEM, SEM, EDS, ED-XRF, XRD, BET and QEA methods. Nanocomposite Ag-SnO2 (12 wt. %). Processing of the initial powder mixture (Ag-SnO2) in nitrogen thermal plasma stream allowed to produce nanopowders with a specific surface area up to 24 m2/g, consisting predominantly of particles with size less than 100 nm. According to XRD results, tin was present in the obtained products as SnO2 phase, and also as intermetallic phases AgxSn. Nanocomposite W-Cu (20 wt .%). Reduction of (WO3+CuO) mixture in the hydrogen-nitrogen plasma provides W-Cu nanopowder with particle sizes in the range of 10-150 nm. The particles have mainly spherical shape and structure tungsten core - copper shell. The thickness of the shell is about several nanometers, the shell is composed of copper and its oxides (Cu2O, CuO). The nanopowders had 1.5 wt. % oxygen impurity. Heat treatment in a hydrogen atmosphere allows to reduce the oxygen content to less than 0.1 wt. %. Nanocomposite Cu-C. Copper nanopowders were found as products of the starting copper compounds decomposition. The nanopowders primarily had a spherical shape with a particle size of less than 100 nm. The main phase was copper, with small amount of Cu2O and CuO oxides. Copper formate decomposition products had a specific surface area 2.5-7 m2/g and contained 0.15 - 4 wt. % carbon; and copper acetate decomposition products had the specific surface area 5-35 m2/g, and carbon content of 0.3 - 5 wt. %. Compacting of nanocomposites (sintering in hydrogen for Ag-SnO2 and electric spark sintering (SPS) for W-Cu) showed that the samples having a relative density of 97-98 % can be obtained with a submicron structure. The studies indicate the possibility of using high-intensity plasma processes to create new technologies to produce nanocomposite materials for electric contacts.

Keywords: electrical contact, material, nanocomposite, plasma, synthesis

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Authors: Mitali Saha, Soma Das

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The fabrication of nanoscale materials for use in chemical sensing, biosensing and biological analyses has proven a promising avenue in the last few years. Cholesterol has aroused considerable interest in recent years on account of its being an important parameter in clinical diagnosis. There is a strong positive correlation between high serum cholesterol level and arteriosclerosis, hypertension, and myocardial infarction. Enzyme-based electrochemical biosensors have shown high selectivity and excellent sensitivity, but the enzyme is easily denatured during its immobilization procedure and its activity is also affected by temperature, pH, and toxic chemicals. Besides, the reproducibility of enzyme-based sensors is not very good which further restrict the application of cholesterol biosensor. It has been demonstrated that carbon nanotubes could promote electron transfer with various redox active proteins, ranging from cytochrome c to glucose oxidase with a deeply embedded redox center. In continuation of our earlier work on the synthesis and applications of carbon and metal based nanoparticles, we have reported here the synthesis of carbon nanotubes (CCNT) by burning coconut oil under insufficient flow of air using an oil lamp. The soot was collected from the top portion of the flame, where the temperature was around 6500C which was purified, functionalized and then characterized by SEM, p-XRD and Raman spectroscopy. The SEM micrographs showed the formation of tubular structure of CCNT having diameter below 100 nm. The XRD pattern indicated the presence of two predominant peaks at 25.20 and 43.80, which corresponded to (002) and (100) planes of CCNT respectively. The Raman spectrum (514 nm excitation) showed the presence of 1600 cm-1 (G-band) related to the vibration of sp2-bonded carbon and at 1350 cm-1 (D-band) responsible for the vibrations of sp3-bonded carbon. A nonenzymatic cholesterol biosensor was then fabricated on an insulating Teflon material containing three silver wires at the surface, covered by CCNT, obtained from coconut oil. Here, CCNTs worked as working as well as counter electrodes whereas reference electrode and electric contacts were made of silver. The dimensions of the electrode was 3.5 cm×1.0 cm×0.5 cm (length× width × height) and it is ideal for working with 50 µL volume like the standard screen printed electrodes. The voltammetric behavior of cholesterol at CCNT electrode was investigated by cyclic voltammeter and differential pulse voltammeter using 0.001 M H2SO4 as electrolyte. The influence of the experimental parameters on the peak currents of cholesterol like pH, accumulation time, and scan rates were optimized. Under optimum conditions, the peak current was found to be linear in the cholesterol concentration range from 1 µM to 50 µM with a sensitivity of ~15.31 μAμM−1cm−2 with lower detection limit of 0.017 µM and response time of about 6s. The long-term storage stability of the sensor was tested for 30 days and the current response was found to be ~85% of its initial response after 30 days.

Keywords: coconut oil, CCNT, cholesterol, biosensor

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Authors: Ekaterina A. Savchenko, Elena N. Velichko, Evgenii T. Aksenov

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The development of pathological processes, such as cardiovascular and oncological diseases, are accompanied by changes in molecular parameters in cells, tissues, and serum. The study of the behavior of protein molecules in solutions is of primarily importance for diagnosis of such diseases. Various physical and chemical methods are used to study molecular systems. With the advent of the laser and advances in electronics, optical methods, such as scanning electron microscopy, sedimentation analysis, nephelometry, static and dynamic light scattering, have become the most universal, informative and accurate tools for estimating the parameters of nanoscale objects. The electrophoretic light scattering is the most effective technique. It has a high potential in the study of biological solutions and their properties. This technique allows one to investigate the processes of aggregation and dissociation of different macromolecules and obtain information on their shapes, sizes and molecular weights. Electrophoretic light scattering is an analytical method for registration of the motion of microscopic particles under the influence of an electric field by means of quasi-elastic light scattering in a homogeneous solution with a subsequent registration of the spectral or correlation characteristics of the light scattered from a moving object. We modified the technique by using the regime of total internal reflection with the aim of increasing its sensitivity and reducing the volume of the sample to be investigated, which opens the prospects of automating simultaneous multiparameter measurements. In addition, the method of total internal reflection allows one to study biological fluids on the level of single molecules, which also makes it possible to increase the sensitivity and the informativeness of the results because the data obtained from an individual molecule is not averaged over an ensemble, which is important in the study of bimolecular fluids. To our best knowledge the study of electrophoretic light scattering in the regime of total internal reflection is proposed for the first time, latex microspheres 1 μm in size were used as test objects. In this study, the total internal reflection regime was realized on a quartz prism where the free electrophoresis regime was set. A semiconductor laser with a wavelength of 655 nm was used as a radiation source, and the light scattering signal was registered by a pin-diode. Then the signal from a photodetector was transmitted to a digital oscilloscope and to a computer. The autocorrelation functions and the fast Fourier transform in the regime of Brownian motion and under the action of the field were calculated to obtain the parameters of the object investigated. The main result of the study was the dependence of the autocorrelation function on the concentration of microspheres and the applied field magnitude. The effect of heating became more pronounced with increasing sample concentrations and electric field. The results obtained in our study demonstrated the applicability of the method for the examination of liquid solutions, including biological fluids.

Keywords: light scattering, electrophoretic light scattering, electrophoresis, total internal reflection

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Authors: Sergio A. Bernal-Chavez, Sergio Alcalá-Alcalá, Doris A. Cerecedo-Mercado, Adriana Ganem-Rondero

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The prevalence of people with chronic wounds has increased dramatically by many factors including smoking, obesity and chronic diseases, such as diabetes, that can slow the healing process and increase the risk of becoming chronic. Because of this situation, the improvement of chronic wound treatments is a necessity, which has led to the scientific community to focus on improving the effectiveness of current therapies and the development of new treatments. The wound formation is a physiological complex process, which is characterized by an inflammatory stage with the presence of proinflammatory cells that create a proteolytic microenvironment during the healing process, which includes the degradation of important growth factors and cytokines. This decrease of growth factors and cytokines provides an interesting strategy for wound healing if they are administered externally. The use of nanometric drug delivery systems, such as polymer nanoparticles (NP), also offers an interesting alternative around dermal systems. An interesting strategy would be to propose a formulation based on a thermosensitive hydrogel loaded with polymeric nanoparticles that allows the inclusion and application of a platelet lysate (PL) on damaged skin, with the aim of promoting wound healing. In this work, NP were prepared by a double emulsion-solvent evaporation technique, using polylactic-co-glycolic acid (PLGA) as biodegradable polymer. Firstly, an aqueous solution of PL was emulsified into a PLGA organic solution, previously prepared in dichloromethane (DCM). Then, this disperse system (W/O) was poured into a polyvinyl alcohol (PVA) solution to get the double emulsion (W/O/W), finally the DCM was evaporated by magnetic stirring resulting in the NP formation containing PL. Once the NP were obtained, these systems were characterized by morphology, particle size, Z-potential, encapsulation efficiency (%EE), physical stability, infrared spectrum, calorimetric studies (DSC) and in vitro release profile. The optimized nanoparticles were included in a thermosensitive gel formulation of Pluronic® F-127. The gel was prepared by the cold method at 4 °C and 20% of polymer concentration. Viscosity, sol-gel phase transition, time of no flow solid-gel at wound temperature, changes in particle size by temperature-effect using dynamic light scattering (DLS), occlusive effect, gel degradation, infrared spectrum and micellar point by DSC were evaluated in all gel formulations. PLGA NP of 267 ± 10.5 nm and Z-potential of -29.1 ± 1 mV were obtained. TEM micrographs verified the size of NP and evidenced their spherical shape. The %EE for the system was around 99%. Thermograms and in infrared spectra mark the presence of PL in NP. The systems did not show significant changes in the parameters mentioned above, during the stability studies. Regarding the gel formulation, the transition sol-gel occurred at 28 °C with a time of no flow solid-gel of 7 min at 33°C (common wound temperature). Calorimetric, DLS and infrared studies corroborated the physical properties of a thermosensitive gel, such as the micellar point. In conclusion, the thermosensitive gel described in this work, contains therapeutic amounts of PL and fulfills the technological properties to be used in damaged skin, with potential application in wound healing and tissue regeneration.

Keywords: growth factors, polymeric nanoparticles, thermosensitive hydrogels, tissue regeneration

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Authors: Moustafa Osman Mohammed

Abstract:

This paper introduces Luhmann’s autopoietic social systems starting with the original concept of autopoiesis by biologists and scientists, including the modification of general systems based on socialized medicine. A specific type of autopoietic system is explained in the three existing groups of the ecological phenomena: interaction, social and medical sciences. This hypothesis model, nevertheless, has a nonlinear interaction with its natural environment ‘interactional cycle’ for the exchange of photon energy with molecular without any changes in topology. The external forces in the systems environment might be concomitant with the natural fluctuations’ influence (e.g. radioactive radiation, electromagnetic waves). The cantilever sensor deploys insights to the future chip processor for prevention of social metabolic systems. Thus, the circuits with resonant electric and optical properties are prototyped on board as an intra–chip inter–chip transmission for producing electromagnetic energy approximately ranges from 1.7 mA at 3.3 V to service the detection in locomotion with the least significant power losses. Nowadays, therapeutic systems are assimilated materials from embryonic stem cells to aggregate multiple functions of the vessels nature de-cellular structure for replenishment. While, the interior actuators deploy base-pair complementarity of nucleotides for the symmetric arrangement in particular bacterial nanonetworks of the sequence cycle creating double-stranded DNA strings. The DNA strands must be sequenced, assembled, and decoded in order to reconstruct the original source reliably. The design of exterior actuators have the ability in sensing different variations in the corresponding patterns regarding beat-to-beat heart rate variability (HRV) for spatial autocorrelation of molecular communication, which consists of human electromagnetic, piezoelectric, electrostatic and electrothermal energy to monitor and transfer the dynamic changes of all the cantilevers simultaneously in real-time workspace with high precision. A prototype-enabled dynamic energy sensor has been investigated in the laboratory for inclusion of nanoscale devices in the architecture with a fuzzy logic control for detection of thermal and electrostatic changes with optoelectronic devices to interpret uncertainty associated with signal interference. Ultimately, the controversial aspect of molecular frictional properties is adjusted to each other and forms its unique spatial structure modules for providing the environment mutual contribution in the investigation of mass temperature changes due to pathogenic archival architecture of clusters.

Keywords: autopoiesis, nanoparticles, quantum photonics, portable energy, photonic structure, photodynamic therapeutic system

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Authors: L. P. Gomes, G. F. Araújo, Y. M. L. Cordeiro, C. T. Andrade, E. M. Del Aguila, V. M. F. Paschoalin

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The application of nanoscale materials and nanostructures is an emerging area, these since materials may provide solutions to technological and environmental challenges in order to preserve the environment and natural resources. To reach this goal, the increasing demand must be accompanied by 'green' synthesis methods. Chitosan is a natural, nontoxic, biopolymer derived by the deacetylation of chitin and has great potential for a wide range of applications in the biological and biomedical areas, due to its biodegradability, biocompatibility, non-toxicity and versatile chemical and physical properties. Chitosan also presents high antimicrobial activities against a wide variety of pathogenic and spoilage microorganisms. Ultrasonication is a common tool for the preparation and processing of polymer nanoparticles. It is particularly effective in breaking up aggregates and in reducing the size and polydispersity of nanoparticles. High-intensity ultrasonication has the potential to modify chitosan molecular weight and, thus, alter or improve chitosan functional properties. The aim of this study was to evaluate the influence of sonication intensity and time on the changes of commercial chitosan characteristics, such as molecular weight and its potential antibacterial activity against Gram-negative bacteria. The nanoparticles (NPs) were produced from two commercial chitosans, of medium molecular weight (CS-MMW) and low molecular weight (CS-LMW) from Sigma-Aldrich®. These samples (2%) were solubilized in 100 mM sodium acetate pH 4.0, placed on ice and irradiated with an ultrasound SONIC ultrasonic probe (model 750 W), equipped with a 1/2" microtip during 30 min at 4°C. It was used on constant duty cycle and 40% amplitude with 1/1s intervals. The ultrasonic degradation of CS-MMW and CS-LMW were followed up by means of ζ-potential (Brookhaven Instruments, model 90Plus) and dynamic light scattering (DLS) measurements. After sonication, the concentrated samples were diluted 100 times and placed in fluorescence quartz cuvettes (Hellma 111-QS, 10 mm light path). The distributions of the colloidal particles were calculated from the DLS and ζ-potential are measurements taken for the CS-MMW and CS-LMW solutions before and after (CS-MMW30 and CS-LMW30) sonication for 30 min. Regarding the results for the chitosan sample, the major bands can be distinguished centered at Radius hydrodynamic (Rh), showed different distributions for CS-MMW (Rh=690.0 nm, ζ=26.52±2.4), CS-LMW (Rh=607.4 and 2805.4 nm, ζ=24.51±1.29), CS-MMW30 (Rh=201.5 and 1064.1 nm, ζ=24.78±2.4) and CS-LMW30 (Rh=492.5, ζ=26.12±0.85). The minimal inhibitory concentration (MIC) was determined using different chitosan samples concentrations. MIC values were determined against to E. coli (106 cells) harvested from an LB medium (Luria-Bertani BD™) after 18h growth at 37 ºC. Subsequently, the cell suspension was serially diluted in saline solution (0.8% NaCl) and plated on solid LB at 37°C for 18 h. Colony-forming units were counted. The samples showed different MICs against E. coli for CS-LMW (1.5mg), CS-MMW30 (1.5 mg/mL) and CS-LMW30 (1.0 mg/mL). The results demonstrate that the production of nanoparticles by modification of their molecular weight by ultrasonication is simple to be performed and dispense acid solvent addition. Molecular weight modifications are enough to provoke changes in the antimicrobial potential of the nanoparticles produced in this way.

Keywords: antimicrobial agent, chitosan, green production, nanoparticles

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Authors: S. B. Q. Tran

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Drop condensation is the phenomenon that the tiny drops form when the oversaturated vapour present in the environment condenses on a substrate and makes the droplet growth. Recently, this subject has received much attention due to its applications in many fields such as thin film growth, heat transfer, recovery of atmospheric water and polymer templating. In literature, many papers investigated theoretically and experimentally in macro droplet growth with the size of millimeter scale of radius. However few papers about nanodroplet condensation are found in the literature especially theoretical work. In order to understand the droplet growth in nanoscale, we perform the numerical simulation work to study nanodroplet growth. We investigate and discuss the role of the droplet shape and monomer diffusion on drop growth and their effect on growth law. The effect of droplet shape is studied by doing parametric studies of contact angle and disjoining pressure magnitude. Besides, the effect of pinning and de-pinning behaviours is also studied. We investigate the axisymmetric homogeneous growth of 10–100 nm single water nanodroplet on a substrate surface. The main mechanism of droplet growth is attributed to the accumulation of laterally diffusing water monomers, formed by the absorption of water vapour in the environment onto the substrate. Under assumptions of quasi-steady thermodynamic equilibrium, the nanodroplet evolves according to the augmented Young–Laplace equation. Using continuum theory, we model the dynamics of nanodroplet growth including the coupled effects of disjoining pressure, contact angle and monomer diffusion with the assumption of constant flux of water monomers at the far field. The simulation result is validated by comparing with the published experimental result. For the case of nanodroplet growth with constant contact angle, our numerical results show that the initial droplet growth is transient by monomer diffusion. When the flux at the far field is small, at the beginning, the droplet grows by the diffusion of initially available water monomers on the substrate and after that by the flux at the far field. In the steady late growth rate of droplet radius and droplet height follow a power law of 1/3, which is unaffected by the substrate disjoining pressure and contact angle. However, it is found that the droplet grows faster in radial direction than high direction when disjoining pressure and contact angle increase. The simulation also shows the information of computational domain effect in the transient growth period. When the computational domain size is larger, the mass coming in the free substrate domain is higher. So the mass coming in the droplet is also higher. The droplet grows and reaches the steady state faster. For the case of pinning and de-pinning droplet growth, the simulation shows that the disjoining pressure does not affect the droplet radius growth law 1/3 in steady state. However the disjoining pressure modifies the growth rate of the droplet height, which then follows a power law of 1/4. We demonstrate how spatial depletion of monomers could lead to a growth arrest of the nanodroplet, as observed experimentally.

Keywords: augmented young-laplace equation, contact angle, disjoining pressure, nanodroplet growth

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Authors: Jessie Rapoza, Petr Moroshkin, Jimmy Xu

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Chirality is omnipresent, in nature, in life, and in the field of physics. One intriguing example is the homochirality that has remained a great secret of life. Another is the pairs of mirror-image molecules – enantiomers. They are identical in atomic composition and therefore indistinguishable in the scalar physical properties. Yet, they can be either therapeutic or toxic, depending on their chirality. Recent studies suggest a potential link between abnormal levels of certain D-amino acids and some serious health impairments, including schizophrenia, amyotrophic lateral sclerosis, and potentially cancer. Although indistinguishable in their scalar properties, the chirality of a molecule reveals itself in interaction with the surrounding of a certain chirality, or more generally, a broken mirror-symmetry. In this work, we report on a system for chiral molecule detection, in which the mirror-symmetry is doubly broken, first by asymmetric structuring a nanopatterned plasmonic surface than by the incidence of circularly polarized light (CPL). In this system, the incident circularly-polarized light induces a surface plasmon polariton (SPP) wave, propagating along the asymmetric plasmonic surface. This SPP field itself is chiral, evanescently bound to a near-field zone on the surface (~10nm thick), but with an amplitude greatly intensified (by up to 104) over that of the incident light. It hence probes just the molecules on the surface instead of those in the volume. In coupling to molecules along its path on the surface, the chiral SPP wave favors one chirality over the other, allowing for chirality detection via the change in an optical rectification current measured at the edges of the sample. The asymmetrically structured surface converts the high-frequency electron plasmonic-oscillations in the SPP wave into a net DC drift current that can be measured at the edge of the sample via the mechanism of optical rectification. The measured results validate these design concepts and principles. The observed optical rectification current exhibits a clear differentiation between a pair of enantiomers. Experiments were performed by focusing a 1064nm CW laser light at the sample - a gold grating microchip submerged in an approximately 1.82M solution of either L-arabinose or D-arabinose and water. A measurement of the current output was then recorded under both rights and left circularly polarized lights. Measurements were recorded at various angles of incidence to optimize the coupling between the spin-momentums of the incident light and that of the SPP, that is, spin-momentum locking. In order to suppress the background, the values of the photocurrent for the right CPL are subtracted from those for the left CPL. Comparison between the two arabinose enantiomers reveals a preferential signal response of one enantiomer to left CPL and the other enantiomer to right CPL. In sum, this work reports on the first experimental evidence of the feasibility of chiral molecule detection via optical rectification in a metal meta-grating. This nanoscale interfaced electrical detection technology is advantageous over other detection methods due to its size, cost, ease of use, and integration ability with read-out electronic circuits for data processing and interpretation.

Keywords: Chirality, detection, molecule, spin

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Authors: Anwar Beg, Sireetorn Kuharat, Rashid Mehmood, Rabil Tabassum, Meisam Babaie

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Nano-polymeric solar paints and sol-gels have emerged as a major new development in solar cell/collector coatings offering significant improvements in durability, anti-corrosion and thermal efficiency. They also exhibit substantial viscosity variation with temperature which can be exploited in solar collector designs. Modern manufacturing processes for such nano-rheological materials frequently employ stagnation flow dynamics under high temperature which invokes radiative heat transfer. Motivated by elaborating in further detail the nanoscale heat, mass and momentum characteristics of such sol gels, the present article presents a mathematical and computational study of the steady, two-dimensional, non-aligned thermo-fluid boundary layer transport of copper metal-doped water-based nano-polymeric sol gels under radiative heat flux. To simulate real nano-polymer boundary interface dynamics, thermal slip is analysed at the wall. A temperature-dependent viscosity is also considered. The Tiwari-Das nanofluid model is deployed which features a volume fraction for the nanoparticle concentration. This approach also features a Maxwell-Garnet model for the nanofluid thermal conductivity. The conservation equations for mass, normal and tangential momentum and energy (heat) are normalized via appropriate transformations to generate a multi-degree, ordinary differential, non-linear, coupled boundary value problem. Numerical solutions are obtained via the stable, efficient Runge-Kutta-Fehlberg scheme with shooting quadrature in MATLAB symbolic software. Validation of solutions is achieved with a Variational Iterative Method (VIM) utilizing Langrangian multipliers. The impact of key emerging dimensionless parameters i.e. obliqueness parameter, radiation-conduction Rosseland number (Rd), thermal slip parameter (α), viscosity parameter (m), nanoparticles volume fraction (ϕ) on non-dimensional normal and tangential velocity components, temperature, wall shear stress, local heat flux and streamline distributions is visualized graphically. Shear stress and temperature are boosted with increasing radiative effect whereas local heat flux is reduced. Increasing wall thermal slip parameter depletes temperatures. With greater volume fraction of copper nanoparticles temperature and thermal boundary layer thickness is elevated. Streamlines are found to be skewed markedly towards the left with positive obliqueness parameter.

Keywords: non-orthogonal stagnation-point heat transfer, solar nano-polymer coating, MATLAB numerical quadrature, Variational Iterative Method (VIM)

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Authors: S. A. Krutovertsev, A. E. Tarasova, L. S. Krutovertseva, O. M. Ivanova

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The aim of the work was to get stable sensitive films with good sensitivity to ethanolamine (C2H7NO) in air. Ethanolamine is used as adsorbent in different processes of gas purification and separation. Besides it has wide industrial application. Chemical sensors of sorption type are widely used for gas analysis. Their behavior is determined by sensor characteristics of sensitive sorption layer. Forming conditions and characteristics of chemical gas sensors based on nanostructured modified silica films activated by different admixtures have been studied. As additives molybdenum containing polyoxometalates of the eighteen series were incorporated in silica films. The method of hydrolythic polycondensation from tetraethyl orthosilicate solutions was used for forming such films in this work. The method’s advantage is a possibility to introduce active additives directly into an initial solution. This method enables to obtain sensitive thin films with high specific surface at room temperature. Particular properties make polyoxometalates attractive as active additives for forming of gas-sensitive films. As catalyst of different redox processes, they can either accelerate the reaction of the matrix with analyzed gas or interact with it, and it results in changes of matrix’s electrical properties Polyoxometalates based films were deposited on the test structures manufactured by microelectronic planar technology with interdigitated electrodes. Modified silica films were deposited by a casting method from solutions based on tetraethyl orthosilicate and polyoxometalates. Polyoxometalates were directly incorporated into initial solutions. Composite nanostructured films were deposited by drop casting method on test structures with a pair of interdigital metal electrodes formed at their surface. The sensor’s active area was 4.0 x 4.0 mm, and electrode gap was egual 0.08 mm. Morphology of the layers surface were studied with Solver-P47 scanning probe microscope (NT-MDT, Russia), the infrared spectra were investigated by a Bruker EQUINOX 55 (Germany). The conditions of film formation varied during the tests. Electrical parameters of the sensors were measured electronically in real-time mode. Films had highly developed surface with value of 450 m2/g and nanoscale pores. Thickness of them was 0,2-0,3 µm. The study shows that the conditions of the environment affect markedly the sensors characteristics, which can be improved by choosing of the right procedure of forming and processing. Addition of polyoxometalate into silica film resulted in stabilization of film mass and changed markedly of electrophysical characteristics. Availability of Mn3P2Mo18O62 into silica film resulted in good sensitivity and selectivity to ethanolamine. Sensitivity maximum was observed at weight content of doping additive in range of 30–50% in matrix. With ethanolamine concentration changing from 0 to 100 ppm films’ conductivity increased by 10-12 times. The increase of sensor’s sensitivity was received owing to complexing reaction of tested substance with cationic part of polyoxometalate. This fact results in intramolecular redox reaction which sharply change electrophysical properties of polyoxometalate. This process is reversible and takes place at room temperature.

Keywords: ethanolamine, gas analysis, polyoxometalate, silica film

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Authors: Yi Li, Rui Lu, Lianjun Wang

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With the rapid development of chemical industry, the consumption of volatile organic compounds (VOCs) has increased extensively. In the process of VOCs production and application, plenty of them have been transferred to environment. As a result, it has led to pollution problems not only in soil and ground water but also to human beings. Thus, it is important to develop a sensitive and cost-effective analytical method for trace VOCs detection in environment. Surface-enhanced Raman Spectroscopy (SERS), as one of the most sensitive optical analytical technique with rapid response, pinpoint accuracy and noninvasive detection, has been widely used for ultratrace analysis. Based on the plasmon resonance on the nanoscale metallic surface, SERS technology can even detect single molecule due to abundant nanogaps (i.e. 'hot spots') on the nanosubstrate. In this work, a self-supported flexible silver nitrate (AgNO3)/ethylene-propylene copolymer (EPM) hybrid nanofibers was fabricated by electrospinning. After an in-situ chemical reduction using ice-cold sodium borohydride as reduction agent, numerous silver nanoparticles were formed on the nanofiber surface. By adjusting the reduction time and AgNO3 content, the morphology and dimension of silver nanoparticles could be controlled. According to the principles of solid-phase extraction, the hydrophobic substance is more likely to partition into the hydrophobic EPM membrane in an aqueous environment while water and other polar components are excluded from the analytes. By the enrichment of EPM fibers, the number of hydrophobic molecules located on the 'hot spots' generated from criss-crossed nanofibers is greatly increased, which further enhances SERS signal intensity. The as-prepared Ag/EPM hybrid nanofibers were first employed to detect common SERS probe molecule (p-aminothiophenol) with the detection limit down to 10-12 M, which demonstrated an excellent SERS performance. To further study the application of the fabricated substrate for monitoring hydrophobic substance in water, several typical VOCs, such as benzene, toluene and p-xylene, were selected as model compounds. The results showed that the characteristic peaks of these target analytes in the mixed aqueous solution could be distinguished even at a concentration of 10-6 M after multi-peaks gaussian fitting process, including C-H bending (850 cm-1), C-C ring stretching (1581 cm-1, 1600 cm-1) of benzene, C-H bending (844 cm-1 ,1151 cm-1), C-C ring stretching (1001 cm-1), CH3 bending vibration (1377 cm-1) of toluene, C-H bending (829 cm-1), C-C stretching (1614 cm-1) of p-xylene. The SERS substrate has remarkable advantages which combine the enrichment capacity from EPM and the Raman enhancement of Ag nanoparticles. Meanwhile, the huge specific surface area resulted from electrospinning is benificial to increase the number of adsoption sites and promotes 'hot spots' formation. In summary, this work provides powerful potential in rapid, on-site and accurate detection of trace VOCs using a portable Raman.

Keywords: electrospinning, ethylene-propylene copolymer, silver nanoparticles, SERS, VOCs

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Authors: Huan Peng, Chenye Zeng, Zhao Wang

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Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

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Authors: Andreea Campu, Ilinica Muresan, Simona Cainap, Simion Astilean, Monica Focsan

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Acute myocardial infarction (AMI) is the most severe cardiovascular disease, which has threatened human lives for decades, thus a continuous interest is directed towards the detection of cardiac biomarkers such as cardiac troponin I (cTnI) in order to predict risk and, implicitly, fulfill the early diagnosis requirements in AMI settings. Microfluidics is a major technology involved in the development of efficient sensing devices with real-time fast responses and on-site applicability. Microfluidic devices have gathered a lot of attention recently due to their advantageous features such as high sensitivity and specificity, miniaturization and portability, ease-of-use, low-cost, facile fabrication, and reduced sample manipulation. The integration of gold nanoparticles into the structure of microfluidic sensors has led to the development of highly effective detection systems, considering the unique properties of the metallic nanostructures, specifically the Localized Surface Plasmon Resonance (LSPR), which makes them highly sensitive to their microenvironment. In this scientific context, herein, we propose the implementation of a novel detection device, which successfully combines the efficiency of gold bipyramids (AuBPs) as signal transducers and thermal generators with the sample-driven advantages of the microfluidic channels into a miniaturized, portable, low-cost, specific, and sensitive test for the dual LSPR-thermographic cTnI detection. Specifically, AuBPs with longitudinal LSPR response at 830 nm were chemically synthesized using the seed-mediated growth approach and characterized in terms of optical and morphological properties. Further, the colloidal AuBPs were deposited onto pre-treated silanized glass substrates thus, a uniform nanoparticle coverage of the substrate was obtained and confirmed by extinction measurements showing a 43 nm blue-shift of the LSPR response as a consequence of the refractive index change. The as-obtained plasmonic substrate was then integrated into a microfluidic “Y”-shaped polydimethylsiloxane (PDMS) channel, fabricated using a Laser Cutter system. Both plasmonic and microfluidic elements were plasma treated in order to achieve a permanent bond. The as-developed microfluidic plasmonic chip was further coupled to an automated syringe pump system. The proposed biosensing protocol implicates the successive injection inside the microfluidic channel as follows: p-aminothiophenol and glutaraldehyde, to achieve a covalent bond between the metallic surface and cTnI antibody, anti-cTnI, as a recognition element, and target cTnI biomarker. The successful functionalization and capture of cTnI was monitored by LSPR detection thus, after each step, a red-shift of the optical response was recorded. Furthermore, as an innovative detection technique, thermal determinations were made after each injection by exposing the microfluidic plasmonic chip to 785 nm laser excitation, considering that the AuBPs exhibit high light-to-heat conversion performances. By the analysis of the thermographic images, thermal curves were obtained, showing a decrease in the thermal efficiency after the anti-cTnI-cTnI reaction was realized. Thus, we developed a microfluidic plasmonic chip able to operate as both LSPR and thermal sensor for the detection of the cardiac troponin I biomarker, leading thus to the progress of diagnostic devices.

Keywords: gold nanobipyramids, microfluidic device, localized surface plasmon resonance detection, thermographic detection

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Authors: Mingqian Zhang

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Tip-enhanced Raman spectroscopy (TERS) is a scanning probe technique for individual objects and structured surfaces investigation that provides a wealth of enhanced spectral information with nanoscale spatial resolution and high detection sensitivity. It has become a powerful and promising chemical and physical information detection method in the nanometer scale. The TERS technique uses a sharp metallic tip regulated in the near-field of a sample surface, which is illuminated with a certain incident beam meeting the excitation conditions of the wave-vector matching. The local electric field, and, consequently, the Raman scattering, from the sample in the vicinity of the tip apex are both greatly tip-enhanced owning to the excitation of localized surface plasmons and the lightning-rod effect. Typically, a TERS setup is composed of a scanning probe microscope, excitation and collection optical configurations, and a Raman spectroscope. In the illumination configuration, an objective lens or a parabolic mirror is always used as the most important component, in order to focus the incident beam on the tip apex for excitation. In this research, a novel TERS setup was built up by introducing a plasmonic lens to the excitation optics as a focusing device. A plasmonic lens with symmetry breaking semi-annular slits corrugated on gold film was designed for the purpose of generating concentrated sub-wavelength light spots with strong longitudinal electric field. Compared to conventional far-field optical components, the designed plasmonic lens not only focuses an incident beam to a sub-wavelength light spot, but also realizes a strong z-component that dominants the electric field illumination, which is ideal for the excitation of tip-enhancement. Therefore, using a PL in the illumination configuration of TERS contributes to improve the detection sensitivity by both reducing the far-field background and effectively exciting the localized electric field enhancement. The FDTD method was employed to investigate the optical near-field distribution resulting from the light-nanostructure interaction. And the optical field distribution was characterized using an scattering-type scanning near-field optical microscope to demonstrate the focusing performance of the lens. The experimental result is in agreement with the theoretically calculated one. It verifies the focusing performance of the plasmonic lens. The optical field distribution shows a bright elliptic spot in the lens center and several arc-like side-lobes on both sides. After the focusing performance was experimentally verified, the designed plasmonic lens was used as a focusing component in the excitation configuration of TERS setup to concentrate incident energy and generate a longitudinal optical field. A collimated linearly polarized laser beam, with along x-axis polarization, was incident from the bottom glass side on the plasmonic lens. The incident light focused by the plasmonic lens interacted with the silver-coated tip apex and enhanced the Raman signal of the sample locally. The scattered Raman signal was gathered by a parabolic mirror and detected with a Raman spectroscopy. Then, the plasmonic lens based setup was employed to investigate carbon nanotubes and TERS experiment was performed. Experimental results indicate that the Raman signal is considerably enhanced which proves that the novel TERS configuration is feasible and promising.

Keywords: longitudinal electric field, plasmonics, raman spectroscopy, tip-enhancement

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Authors: Fadi Al Khatib, Raouf Mbarki, Malek Adouni

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In various sport and recreational activities, the patellofemoral joint undergoes large forces and moments while accommodating the significant knee joint movement. In doing so, this joint is commonly the source of anterior knee pain related to instability in normal patellar tracking and excessive pressure syndrome. One well-observed explanation of the instability of the normal patellar tracking is the patellofemoral ligaments and patellar tendon damage. Improved knowledge of the damage mechanism mediating ligaments and tendon injuries can be a great help not only in rehabilitation and prevention procedures but also in the design of better reconstruction systems in the management of knee joint disorders. This damage mechanism, specifically due to excessive mechanical loading, has been linked to the micro level of the fibred structure precisely to the tropocollagen molecules and their connection density. We argue defining a clear frame starting from the bottom (micro level) to up (macro level) in the hierarchies of the soft tissue may elucidate the essential underpinning on the state of the ligaments damage. To do so, in this study a multiscale fibril reinforced hyper elastoplastic Finite Element model that accounts for the synergy between molecular and continuum syntheses was developed to determine the short-term stresses/strains patellofemoral ligaments and tendon response. The plasticity of the proposed model is associated only with the uniaxial deformation of the collagen fibril. The yield strength of the fibril is a function of the cross-link density between tropocollagen molecules, defined here by a density function. This function obtained through a Coarse-graining procedure linking nanoscale collagen features and the tissue level materials properties using molecular dynamics simulations. The hierarchies of the soft tissues were implemented using the rule of mixtures. Thereafter, the model was calibrated using a statistical calibration procedure. The model then implemented into a real structure of patellofemoral ligaments and patellar tendon (OpenKnee) and simulated under realistic loading conditions. With the calibrated material parameters the calculated axial stress lies well with the experimental measurement with a coefficient of determination (R2) equal to 0.91 and 0.92 for the patellofemoral ligaments and the patellar tendon respectively. The ‘best’ prediction of the yielding strength and strain as compared with the reported experimental data yielded when the cross-link density between the tropocollagen molecule of the fibril equal to 5.5 ± 0.5 (patellofemoral ligaments) and 12 (patellar tendon). Damage initiation of the patellofemoral ligaments was located at the femoral insertions while the damage of the patellar tendon happened in the middle of the structure. These predicted finding showed a meaningful correlation between the cross-link density of the tropocollagen molecules and the stiffness of the connective tissues of the extensor mechanism. Also, damage initiation and propagation were documented with this model, which were in satisfactory agreement with earlier observation. To the best of our knowledge, this is the first attempt to model ligaments from the bottom up, predicted depending to the tropocollagen cross-link density. This approach appears more meaningful towards a realistic simulation of a damaging process or repair attempt compared with certain published studies.

Keywords: tropocollagen, multiscale model, fibrils, knee ligaments

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Authors: Roshni Raha, Kavya P., Gayathri M.

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India, with a humongous population, remains the world's poorest developing nation in terms of nutritional status, with iron deficiency anaemia (IDA) affecting the population. Despite efforts over the past decades, India's anaemia prevalence has not been reduced. Researchers are interested in developing therapies that will minimize the typical side effects of oral iron and optimize iron salts-based treatment through delivery methods based on the physiology of hepcidin regulation. However, they need to come up with iron therapies that will prevent making the infection worse. This article explores using bio-nanotechnology as the alternative, promising substitution of providing iron supplements for the treatment of diarrhoea and gut inflammation in kids and pregnant women. This article is an exploratory study using a literature survey and secondary research from review papers. In the realm of biotechnology, nanoparticles have become extremely famous due to unexpected variations in surface characteristics caused by particle size. Particle size distribution and shape exhibit unusual, enhanced characteristics when reduced to nanoscale. The article attempts to develop a model for a nanotechnology based solution in iron fortification to combat the problems of diarrhoea and gut inflammation. Certain dimensions that have been considered in the model include the size, shape, source, and biosynthesis of the iron nanoparticles. Another area of investigation addressed in the article is the cost-effective biocompatible production of these iron nanoparticles. Studies have demonstrated that a substantial reduction of metal ions to form nanoparticles from the bulk metal occurs in plants because of the presence of a wide diversity of biomolecules. Using this concept, the paper investigates the effectiveness and impact of how similar sources can be used for the biological synthesis of iron nanoparticles. Results showed that iron particles, when prepared in nano-metre size, offer potential advantages. When the particle size of the iron compound decreases and attains nano configuration, its surface area increases, which further improves its solubility in the gastric acid, leading to higher absorption, higher bioavailability, and producing the least organoleptic changes in food. It has no negative effects and possesses a safe, effective profile to reduce IDA. Considering all the parameters, it has been concluded that iron particles in nano configuration serve as alternative iron supplements for the complete treatment of IDA. Nanoparticles of ferric phosphate, ferric pyrophosphate, and iron oxide are the choices of iron supplements. From a sourcing perspective, the paper concludes green sources are the primary sources for the biological synthesis of iron nanoparticles. It will also be a cost-effective strategy since our goal is to treat the target population in rural India. Bio-nanotechnology serves as an alternative and promising substitution for iron supplements due to its low cost, excellent bioavailability, and strong organoleptic properties. One area of future research can be to explore the type of size and shape of iron nanoparticles that would be suitable for the different age groups of pregnant women and children and whether it would be influenced based on the topography in certain areas.

Keywords: anemia, bio-nanotechnology, iron-fortification, nanoparticle

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Authors: Nino Kupatadze, Tamar Memanishvili, Natia Ochkhikidze, David Tugushi, Zaal Kokaia, Ramaz Katsarava

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Amino acid-based Biodegradable poly(ester-amide)s (PEAs) have gained considerable interest as a promising materials for numerous biomedical applications. These polymers reveal a high biocompatibility and easily form small particles suitable for delivery various biological, as well as elastic bio-erodible films serving as matrices for constructing antibacterial coatings. In the present work we have demonstrated a potential of the PEAs for two applications: 1. cell therapy for stroke as vehicles for delivery and sustained release of growth factors, 2. bactericidal coating as prevention biofilm and applicable in infected wound management. Stroke remains the main cause of adult disability with limited treatment options. Although stem cell therapy is a promising strategy, it still requires improvement of cell survival, differentiation and tissue modulation. .Recently, microspheres (MPs) made of biodegradable polymers have gained significant attention for providing necessary support of transplanted cells. To investigate this strategy in the cell therapy of stroke, MPs loaded with transcription factors Wnt3A/BMP4 were prepared. These proteins have been shown to mediate the maturation of the cortical neurons. We have suggested that implantation of these materials could create a suitable microenvironment for implanted cells. Particles with spherical shape, porous surface, and 5-40 m in size (monitored by scanning electron microscopy) were made on the basis of the original PEA composed of adipic acid, L-phenylalanine and 1,4-butanediol. After 4 months transplantation of MPs in rodent brain, no inflammation was observed. Additionally, factors were successfully released from MPs and affected neuronal cell differentiation in in vitro. The in vivo study using loaded MPs is in progress. Another severe problem in biomedicine is prevention of surgical devices from biofilm formation. Antimicrobial polymeric coatings are most effective “shields” to protect surfaces/devices from biofilm formation. Among matrices for constructing the coatings preference should be given to bio-erodible polymers. Such types of coatings will play a role of “unstable seating” that will not allow bacteria to occupy the surface. In other words, bio-erodible coatings would be discomfort shelter for bacteria that along with releasing “killers of bacteria” should prevent the formation of biofilm. For this purpose, we selected an original biodegradable PEA composed of L-leucine, 1,6-hexanediol and sebacic acid as a bio-erodible matrix, and nanosilver (AgNPs) as a bactericidal agent (“killer of bacteria”). Such nanocomposite material is also promising in treatment of superficial wound and ulcer. The solubility of the PEA in ethanol allows to reduce AgNO3 to NPs directly in the solution, where the solvent served as a reductive agent, and the PEA served as NPs stabilizer. The photochemical reduction was selected as a basic method to form NPs. The obtained AgNPs were characterized by UV-spectroscopy, transmission electron microscope (TEM), and dynamic light scattering (DLS). According to the UV-data and TEM data the photochemical reduction resulted in spherical AgNPs with wide particle size distribution with a high contribution of the particles below 10 nm that are known as responsible for bactericidal activity of AgNPs. DLS study showed that average size of nanoparticles formed after photo-reduction in ethanol solution ranged within ca. 50 nm.

Keywords: biodegradable polymers, microparticles, nanocomposites, stem cell therapy, stroke

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Authors: Wonil Nam, Xiang Ren, Inyoung Kim, Masoud Agah, Wei Zhou

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Despite its ultrasensitive detection capability, surface-enhanced Raman spectroscopy (SERS) faces challenges as a quantitative biochemical analysis tool due to the significant dependence of local field intensity in hotspots on nanoscale geometric variations of plasmonic nanostructures. Therefore, despite enormous progress in plasmonic nanoengineering of high-performance SERS devices, it is still challenging to quantitatively correlate the measured SERS signals with the actual molecule concentrations at hotspots. A significant effort has been devoted to developing SERS calibration methods by introducing internal standards. It has been achieved by placing Raman tags at plasmonic hotspots. Raman tags undergo similar SERS enhancement at the same hotspots, and ratiometric SERS signals for analytes of interest can be generated with reduced dependence on geometrical variations. However, using Raman tags still faces challenges for real-world applications, including spatial competition between the analyte and tags in hotspots, spectral interference, laser-induced degradation/desorption due to plasmon-enhanced photochemical/photothermal effects. We show that electronic Raman scattering (ERS) signals from metallic nanostructures at hotspots can serve as the internal calibration standard to enable quantitative SERS analysis and improve biostatistical analysis. We perform SERS with Au-SiO₂ multilayered metal-insulator-metal nano laminated plasmonic nanostructures. Since the ERS signal is proportional to the volume density of electron-hole occupation in hotspots, the ERS signals exponentially increase when the wavenumber is approaching the zero value. By a long-pass filter, generally used in backscattered SERS configurations, to chop the ERS background continuum, we can observe an ERS pseudo-peak, IERS. Both ERS and SERS processes experience the |E|⁴ local enhancements during the excitation and inelastic scattering transitions. We calibrated IMRS of 10 μM Rhodamine 6G in solution by IERS. The results show that ERS calibration generates a new analytical value, ISERS/IERS, insensitive to variations from different hotspots and thus can quantitatively reflect the molecular concentration information. Given the calibration capability of ERS signals, we performed label-free SERS analysis of living biological systems using four different breast normal and cancer cell lines cultured on nano-laminated SERS devices. 2D Raman mapping over 100 μm × 100 μm, containing several cells, was conducted. The SERS spectra were subsequently analyzed by multivariate analysis using partial least square discriminant analysis. Remarkably, after ERS calibration, MCF-10A and MCF-7 cells are further separated while the two triple-negative breast cancer cells (MDA-MB-231 and HCC-1806) are more overlapped, in good agreement with the well-known cancer categorization regarding the degree of malignancy. To assess the strength of ERS calibration, we further carried out a drug efficacy study using MDA-MB-231 and different concentrations of anti-cancer drug paclitaxel (PTX). After ERS calibration, we can more clearly segregate the control/low-dosage groups (0 and 1.5 nM), the middle-dosage group (5 nM), and the group treated with half-maximal inhibitory concentration (IC50, 15 nM). Therefore, we envision that ERS calibrated SERS can find crucial opportunities in label-free molecular profiling of complicated biological systems.

Keywords: cancer cell drug efficacy, plasmonics, surface-enhanced Raman spectroscopy (SERS), SERS calibration

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