Project description:Characterizing nanomaterials is challenging due to their macromolecular nature, requiring suites of physicochemical analysis to fully resolve their structure. As such, their synthesis and scale-up are notoriously complex, especially when compared to small molecules or bulk crystalline materials, which can be provided a unique fingerprint from nuclear magnetic resonance (NMR) or X-ray diffraction (XRD) alone. In this study, we address this challenge by adopting a three-step quality-by-design (QbD) approach to the scale-up of bioinspired silica nanomaterials, demonstrating its utility toward synthesis scale-up and intensification for this class of materials in general. First, we identified material-specific surface area, pore-size distribution, and reaction yield as critical quality attributes (CQAs) that could be precisely measured and controlled by changing reaction conditions. We then identified the critical process parameters (CPPs) controlling bioinspired synthesis properties, exploring different process routes, incorporating commercial reagents, and optimizing reagent ratios, comparing silica properties against original CQA values to identify acceptable limits to each CPP. Finally, we intensified the synthesis by increasing reagent concentration while simultaneously incorporating the optimized CPPs, thereby modifying the bioinspired silica synthesis to make it compatible with existing manufacturing methods. We increased the specific yield from ca. 1.1 to 38 g/L and reduced the additive intensity from ca. 1 to 0.04 g/g product, greatly reducing both synthesis cost and waste production. These results identify a need for mapping the effects of critical process parameters on material formation pathways and CQAs to enable accelerated scale-up and transition from the lab to the market.
Project description:Noble metal nanostructures have been intensively investigated as active substrates for surface-enhanced Raman spectroscopy (SERS) from visible to near-IR wavelengths. However, metal nanoparticle-based SERS analysis in solutions is very challenging due to uncontrollable and irreproducible colloid aggregation. Here we report the templated synthesis of porous gold-silica hybrid microspheres and their application as reusable colloidal SERS substrates. Mesoporous polymer microspheres are synthesized and used as templates for the synthesis of non-aggregated gold nanoparticles, followed by polydopamine-mediated silicification to fabricate mesoporous gold-silica hybrid microspheres. The mesoporous hybrid particles detect crystal violet in the order of 10-8 M and provide the structural durability of the immobilized gold nanoparticles, allowing them to be recycled for repeated SERS analyses for analytes in a solution with the similar sensitivity. This work suggests that the mesoporous gold-silica hybrid microspheres are attractive SERS substrates in terms of reusability, sensitivity, and stability.
Project description:Cellulases are enzymes with great potential for converting biomass to biofuels for sustainable energy. However, their commercial use is limited by their costs and low reusability. Therefore, the scientific and industrial sectors are focusing on finding better strategies to reuse enzymes and improve their performance. In this work, cellulase from Aspergillus niger was immobilised through in situ entrapment and adsorption on bio-inspired silica (BIS) supports. To the best of our knowledge, this green effect strategy has never been applied for cellulase into BIS. In situ entrapment was performed during support synthesis, applying a one-pot approach at mild conditions (room temperature, pH 7, and water solvent), while adsorption was performed after support formation. The loading efficiency was investigated on different immobilisation systems by Bradford assay and FTIR. Bovine serum albumin (BSA) was chosen as a control to optimize cellulase loading. The residual activity of cellulase was analysed by the dinitro salicylic acid (DNS) method. Activity of 90% was observed for the entrapped enzyme, while activity of ~55% was observed for the adsorbed enzyme. Moreover, the supported enzyme systems were recycled five times to evaluate their reuse potential. The thermal and pH stability tests suggested that both entrapment and adsorption strategies can increase enzyme activity. The results highlight that the entrapment in BIS is a potentially useful strategy to easily immobilise enzymes, while preserving their stability and recycle potential.
Project description:A simple, efficient, and selective oxidation under flow conditions of sulfides into their corresponding sulfoxides and sulfones is reported herein, using as a catalyst perselenic acid generated in situ by the oxidation of selenium (IV) oxide in a diluted aqueous solution of hydrogen peroxide as the final oxidant. The scope of the proposed methodology was investigated using aryl alkyl sulfides, aryl vinyl sulfides, and dialkyl sulfides as substrates, evidencing, in general, a good applicability. The scaled-up synthesis of (methylsulfonyl)benzene was also demonstrated, leading to its gram-scale preparation.
Project description:Elevated core temperature constitutes an important biomarker for COVID-19 infection; however, no standards currently exist to monitor fever using wearable peripheral temperature sensors. Evidence that sensors could be used to develop fever monitoring capabilities would enable large-scale health-monitoring research and provide high-temporal resolution data on fever responses across heterogeneous populations. We launched the TemPredict study in March of 2020 to capture continuous physiological data, including peripheral temperature, from a commercially available wearable device during the novel coronavirus pandemic. We coupled these data with symptom reports and COVID-19 diagnosis data. Here we report findings from the first 50 subjects who reported COVID-19 infections. These cases provide the first evidence that illness-associated elevations in peripheral temperature are observable using wearable devices and correlate with self-reported fever. Our analyses support the hypothesis that wearable sensors can detect illnesses in the absence of symptom recognition. Finally, these data support the hypothesis that prediction of illness onset is possible using continuously generated physiological data collected by wearable sensors. Our findings should encourage further research into the role of wearable sensors in public health efforts aimed at illness detection, and underscore the importance of integrating temperature sensors into commercially available wearables.
Project description:Iron has been used previously in water decontamination, either unsupported or supported on clays, polymers, carbons or ceramics such as silica. However, the reported synthesis procedures are tedious, lengthy (involving various steps), and either utilise or produce toxic chemicals. Herein, the use of a simple, rapid, bio-inspired green synthesis method is reported to prepare, for the first time, a family of iron supported on green nanosilica materials (Fe@GN) to create new technological solutions for water remediation. In particular, Fe@GN were employed for the removal of arsenate ions as a model for potentially toxic elements in aqueous solution. Several characterization techniques were used to study the physical, structural and chemical properties of the new Fe@GN. When evaluated as an adsorption platform for the removal of arsenate ions, Fe@GN exhibited high adsorption capacity (69 mg of As per g of Fe@GN) with superior kinetics (reaching ∼35 mg As per g sorbent per hr) - threefold higher than the highest removal rates reported to date. Moreover, a method was developed to regenerate the Fe@GN allowing for a full recovery and reuse of the adsorbent in subsequent extractions; strongly highlighting the potential technological benefits of these new green materials.
Project description:In this work, cellular silica was synthesized by using microbubbles as templates, which contain a mixture of argon and silicon tetrafluoride (SiF4). The latter is generated from decomposition of hexafluorosilicic acid (H2SiF6) at ambient conditions. The specific surface area of cellular silica can be as high as 130 m2/g, the size of the cavity is hundreds-of-nanometers, and the thickness of the cavity wall is around 30 nm. The cavity size, apparent packing density, and porosity of cellular silica strongly depend on the nature of the aqueous solutions; the cavity size appears to be negatively proportional to the surface tension, but thickness of cavity walls seems to be weakly affected by the aqueous properties. An attempt was made to introduce aluminum atoms in situ in the second-coordination sphere of Si atoms and/or load aluminum into the silica structure. Cellular silica with large pores facilitate the transfer of large molecules, including polymers and enzymes; thus, it could find applications in (bio)catalysis, sorption, controlled release and separations.
Project description:In recent years, there has been a breakthrough in the integration of artificial nanoplatforms with natural biomaterials for the development of more efficient drug delivery systems. The formulation of bioinspired nanosystems, combining the benefits of synthetic nanoparticles with the natural features of biological materials, provides an efficient strategy to improve nanoparticle circulation time, biocompatibility and specificity toward targeted tissues. Among others biological materials, extracellular vesicles (EVs), membranous structures secreted by many types of cells composed by a protein rich lipid bilayer, have shown a great potential as drug delivery systems themselves and in combination with artificial nanoparticles. The reason for such interest relays on their natural properties, such as overcoming several biological barriers or migration towards specific tissues. Here, we propose the use of mesoporous silica nanoparticles (MSNs) as efficient and versatile nanocarriers in combination with tumor derived extracellular vesicles (EVs) for the development of selective drug delivery systems. The hybrid nanosystems demonstrated selective cellular internalization in parent cells, indicating that the EV targeting capabilities were efficiently transferred to MSNs by the developed coating strategy. As a result, EVs-coated MSNs provided an enhanced and selective intracellular accumulation of doxorubicin and a specific cytotoxic activity against targeted cancer cells, revealing these hybrid nanosystems as promising candidates for the development of targeted treatments.
Project description:The combination of electrocyclizations and cycloadditions accounts for the formation of a range of fascinating natural products. Cascades consisting of 8π electrocyclizations followed by a 6π electrocyclization and a cycloaddition are relatively common. We now report the synthesis of the tetramic acid PF-1018 through an 8π electrocyclization, the product of which is immediately intercepted by a Diels-Alder cycloaddition. The success of this pericyclic cascade was critically dependent on the substitution pattern of the starting polyene and could be rationalized through DFT calculations. The completion of the synthesis required the instalment of a trisubstituted double bond by radical deoxygenation. An unexpected side product formed through 4-exo-trig radical cyclization could be recycled through an unprecedented triflation/fragmentation.
Project description:Microfluidics brings unique opportunities for engineering micro-/nanomaterials with well-controlled physicochemical properties. Herein, using a miniaturized multi-run spiral-shaped microreactor, we develop a flow synthesis strategy to continuously produce hollow spherical silica (HSS) with hierarchical sponge-like pore sizes ranging from several nanometers to over one hundred nanometers. The formation of HSS is realized by mixing two reactant flows, one containing cetyltrimethylammonium bromide (CTAB) and diluted ammonia and the other 1,3,5-trimethylbenzene (TMB) and diluted tetraethyl orthosilicate (TEOS), at a flow rate as high as 5 mL/min. The effect of the reactant concentration and the flow rate on the structural change of the resultant materials is examined. Functional small-sized nanoparticles (magnetic nanoparticle, quantum dot, and silver nanoparticle) can be separately assembled into HSS and high molecular weight protein (bovine serum albumin) can be successfully loaded into HSS and delivered into cancer cells afterward, making them promising in the fields of separation and purification, bioimaging, catalysis, and theranostics.