Reaction engineering approach to the flow synthesis of nanomaterials for sensing and biomedical applications

Nanomaterials promise to revolutionize technologies belonging to many different fields thanks to their peculiar properties arising from their small size, at the interface between that of molecules and that of particles, high surface area and distinctive optical and electronic properties. Some nanomaterials-based products started appearing on the market over the last two decades. However, a striking difference still exists between the number of nanomaterials-focused scientific contributions being published and the number of nanomaterials-based products currently sold, with full exploitation of the benefits coming from the use of nanomaterials in everyday life still far from happening. This distance between science and the market appears even more evident in the field of biomedicine. Different reasons hide behind the very low ratio between available nanomaterials-based medical products and scientific effort in the field. One of these reasons is the difficulty in manufacturing these materials in a reproducible manner and on a sufficiently large scale. Scale-up of these productions often leads to irreproducible results and a lack of the desired materials properties, especially when facing the strict regulations for medical application. Conventional manufacturing strategies based on the use of batch systems suffer from batch-to-batch variability, caused by slow and irreproducible mixing and inhomogeneous temperature profile. Flow reactors represent a solution to these issues, thanks to their high surface area, product volumes higher than reactor volume, and reduced human intervention during operation. Over the last decade, the number of works regarding flow synthesis of nanomaterials exponentially increased. Nonetheless, a formal design protocol for such reactors is still not available, with researchers relying on a pure black-box approach. This approach is experimentally intensive and case dependent, complicating the scale-up of the reactors. Difficulties arise also in implementing model-based control systems, essential in industrial settings. The aim of this thesis is to develop a design approach for flow reactors synthesizing nanomaterials based on the combination of kinetics studies and classic reactor design principles. A theoretical background was first established using the well-studied synthesis of silica nanoparticles. A model was developed demonstrating the possibility of describing the reactor behaviour through the combination of residence time distribution theory and kinetic data obtained in batch. Supported by this theoretical background, the thesis shows the successful attempt at designing two flow reactors for the synthesis and growth of gold nanoparticles, eventually enabling control over the particle size between 10 and 150 nm, as well as granting high synthesis reproducibility (with deviation in the average size between runs in the order of ). The reactor design used to develop these reactors started from kinetic data acquired in batch via in situ time- 4 resolved UV-Vis spectroscopy, which are used to determine the process operating conditions of the flow reactor. The first reactor designed for the synthesis of gold nanoparticles produced 11 nm gold seeds through a modified Turkevich method developed in this thesis, named passivated Turkevich method, where the precursor coordination sphere is engineered to maximize the synthesis reproducibility. The second reactor developed in this thesis uses the seeds produced by the first reactor and grows them to a controllable final size (up to 150 nm) in a single growth step. The growth was performed through a different synthetic protocol, and again, the design of the reactor followed the same principles, starting with the study of the synthesis kinetics in batch via in situ time-resolved UV-Vis spectroscopy, showing the flexibility of the proposed reactor design approach. To obtain a detailed description of the particle evolution during their synthesis, this thesis also focused on the development of a model for the interpretation of the time-resolved UV-Vis data obtained during the synthesis of Au nanoparticles. The developed model renders the evolution of the particle size and number density during the synthesis. This model also explains the distinctive evolution of the Au nanoparticles optical properties observed during the Turkevich synthesis, with the peak absorbance moving from low to high energies. This phenomenon is explained through the adsorption of Au precursor species on the surface of the growing nanoparticles, which induces a change in the particle free electron density. The model reconciles in this way the latest mechanistic studies of the Turkevich synthesis (where no particle aggregates are observed) with the Mie theory. The design approach proposed in the thesis is useful for the translation of nanomaterials synthesis from batch to flow. However, flow reactors can access operating conditions hardly achievable in batch, possibly enabling new nanomaterials syntheses or further optimization of existing ones. This was demonstrated in this thesis for the synthesis of iron oxide nanoparticles, where flow reactors allowed the straightforward introduction in the aqueous system of gaseous reactants at high pressures and temperatures. Four reactor systems were designed by a combination of two modules, namely a membrane gas-liquid contactor and a reaction coil. These reactor systems allowed control over the flow profile, use of gaseous reactants as well as access to temperatures above the solvent boiling point through straightforward system pressurization. Control over these variables led to a significant decrease in the reaction time (from several hours down to 3 min) and control over particle crystal structure, size, and morphology. Finally, one of these reactor systems was scaled up by a factor of 5 without loss in product quality. The advantages of flow reactors to perform synthesis aided by low penetration depth radiations was then explored. Microwave heating is currently attracting attention as an alternative heating 5 technology which could allow faster heating rates and more homogeneous temperature profiles in large scale flow systems as a result of the bulk microwave heating mechanism, against surface-mediated conventional heating. This thesis investigated the use of microwave heating to perform the synthesis of iron oxide nanoparticles via the aqueous coprecipitation of iron chlorides in basic media, followed by stabilization through the addition of citric acid and dextran. The microwave synthesis led to the generation of multicore assemblies of iron oxide nanoparticles with a similar single-core size of conventionally produced ones, but with significantly larger hydrodynamic diameters. This suggests changes possibly induced by either the different heating profiles or the microwave radiation itself in the nucleation and aggregation rates, which determine the final assembly size. The scale-up of the microwave reactor was then investigated, with a successful increase in the production rate by a factor of 8. Eventually, the development of a new synthetic protocol for the synthesis of thermoresponsive magnetic nanogels and its translation from batch to flow are presented. This nanomaterial is developed through a bottom-up approach studying the synthesis of each unit composing the final product. The core of this material comprises iron oxide nanoparticles, produced via flow chemistry: different particles were screened with varying size and surface chemistry. Colloidal stability and hydrophobicity of the coating determined the successful encapsulation of the particles in the nanogel. In parallel, the nanogel formulation was optimized to achieve the desired size and transition temperature for the eventual temperature-triggered drug release application. The coating kinetics were studied, demonstrating that the synthesis finishes after ~5-10 min, a much shorter reaction time than those normally employed in the literature. The kinetics information is then used to guide the design of a single-phase flow reactor producing said nanomaterial, leading to a g/day production scale in a lab setting

Efficacy and tolerability of a topical gel containing 3% hydrogen peroxide, 1.5% salicylic acid and 4% D-panthenol in the treatment of mild-moderate acne

The aim of this paper was to evaluate efficacy and tolerability of a topical gel (ACNAID TM gel medical device) containing 3% hydrogen peroxide (HPO), 1.5% salicylic acid (SA) and 4% D-panthenol (D-p) in the treatment of mild-moderate acne, comparing it with a previous formulation (ACNAID TM gel Cosmetic) containing 4% HPO, 0.5% SA, 4% D-p

User-centered approach for design and development of industrial workplace

AbstractIn this paper, we propose a user-centered approach for the design of ergonomic workplaces. The method is based on the evaluation of subjective opinions and objective measures from the worker, while performing the industrial tasks. The ergonomic design of industrial workplaces will have impact in reducing the musculoskeletal disorders of workers

Comprehensive biomedical applications of low temperature plasmas

This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.The main component of plasma medicine is the use of low-temperature plasma (LTP) as a powerful tool for biomedical applications. LTP generates high reactivity at low temperatures and can be activated with noble gases with molecular mixtures or compressed air. LTP reactive species are quickly produced, and are a remarkably good source of reactive oxygen and nitrogen species including singlet oxygen (O2), ozone (O3), hydroxyl radicals (OH), nitrous oxide (NO), and nitrogen dioxide (NO2). Its low gas temperature and highly reactive non-equilibrium chemistry make it appropriate for the alteration of inorganic surfaces and delicate biological systems. Treatment of oral biofilm-related infections, treatment of wounds and skin diseases, assistance in cancer treatment, treatment of viruses’ infections (e.g. herpes simplex), and optimization of implants surfaces are included among the extensive plasma medicine applications. Each of these applications will be discussed in this review article.This work was supported by the National Institute of Health/National Institute of Dental and Craniofacial Research, NIH/NIDCR – 1R21DE028929-01)

Hydrogeology and Hydrogeochemistry of the Lauria Mountains Northern Sector Groundwater Resources (Basilicata, Italy)

In this study, the hydrogeological characterization of the northern sector of the Lauria Mounts carbonate hydrostructure (southern Apennines, Basilicata region) has been carried out and the hydrochemical properties of different collected groundwater samples have been characterized. Several normal springs drain the hydrostructure, some of them characterized by high annual mean discharges. Groundwater samples were collected from different springs; many parameters such as pH, electrical conductivity, and total dissolved solids have been measured, and major (cations and anions) elements and stable isotopes have been analysed following standard test procedures. Other chemical characteristics were derived from the analysed quality parameters. The results elucidate that the main hydrogeochemical processes control the chemical content and assess the quality of the groundwater within the hydrostructure. The analyses highlight that the chemical compositions of groundwater are strongly influenced by the lithology, especially limestones and dolomitic limestones; they explain and confirm the hydrogeological setting of the system. The groundwater system displays light different geochemical signatures. The processes contributing to the concentrations of major ions depend primarily on carbonate dissolution. The analysis, in all studied groundwater samples, shows that the facies groundwater type is Ca–HCO3, bicarbonate is the dominant anion, and calcium is the dominant cation with appreciable magnesium concentrations. To identify the aquifer's recharge areas, the environmental stable isotopes oxygen and hydrogen, deuterium, and 18O were analysed. The unaltered δ18O and δD signatures for the groundwater of the major springs allows identifying the recharge area of these emergencies at elevations ranging from 900 m to 1000 m (a.s.l.), pointing out the presence of deeper flow regime feeding of these springs. The groundwater sample isotopic characteristics of D and 18O suggest that most of the groundwater is recharged directly by infiltration in a high-permeability medium

Gas-phase diagnostics by laser-induced gratings II. Experiments

In this article we review the results achieved in the past ten years at the Paul Scherrer Institute on the topic of diagnostics in the gas phase by laser-induced gratings (LIGs). The technique has been applied for thermometry in air and in flames at different pressures, for flow velocimetry, for concentration measurements, and for imaging purposes. The influence of collisional energy-transfer and relaxation processes in molecules on the temporal evolution of the LIG signals has also been investigated. It has been demonstrated that, for molecules with a low fluorescence quantum yield, excitation of laser-induced thermal gratings can be used as a sensitive spectroscopic tool. For the quantitative interpretation of the experiments shown in this work, the findings presented in the companion paper [1] have been use

Gas phase diagnostics by laser-induced gratings I. theory

Electrostriction and collisional thermalization of absorbed laser energy are the two dominant mechanisms leading to the formation of laser-induced gratings (LIGs) in the gas phase. In this article the results of the theoretical investigations that have been achieved in the past ten years at the Paul Scherrer Institute on this issue are summarized and yield a comprehensive understanding of the underlying physical concepts. Furthermore, a study of the influence of various parameters, such as the alignment and the spatial intensity profile of the beams on the generated electrostrictive and thermal signal is presented for the first time to the authors' knowledge. The variations of the refractive index responsible for the appearance of laser-induced gratings have been theoretically described by solving the linearized hydrodynamic equations. The contributions from electrostriction, as well as from instantaneous and slow relaxation of the absorbed radiation energy into heat is obtained. These expressions are employed for analysis of experimental data presented in the companion paper [1] which is devoted to the application of the technique for diagnostic purposes in the gas phase. Much effort has been undertaken in order to allow a straightforward physical interpretation of the experimental findings of the expressions presented her

Identification of a Novel Retinoic Acid Response Element in the Promoter Region of the Retinol-binding Protein Gene

We have previously demonstrated that the retinol-binding protein (RBP) gene is induced by retinoids in hepatoma cells. In this report, we define in greater detail the region that mediates the retinoic acid response of the gene. It consists of two degenerate retinoic acid response elements, separated by 30 nucleotides that encompass a GC-rich Sp1 consensus-like sequence. We demonstrate that the entire region, as well as each element taken singly, can bind the retinoic acid receptors as homo- and heterodimers with low affinity. However, only the entire region is able to confer retinoic acid inducibility to a heterologous promoter. We also show that the correct phasing of the DNA segment is necessary to achieve full responsiveness. Site-directed mutants in each element retained partial induction after transfection, while the double mutant was no longer responsive, suggesting that the two elements act synergistically. Mutational analysis of the Sp1 binding site and cotransfection experiments revealed that Sp1 or a related protein plays an important role in the transcription of the gene. Thus, the retinoic acid induction of the RBP gene is mediated by a novel and complex responsive unit formed by two distinct elements located in a specific sequence context and the interplay of the retinoid receptors with Sp1 is required for induction