A Modular Millifluidic Platform for the Synthesis of Iron Oxide Nanoparticles with Control over Dissolved Gas and Flow Configuration

Gas–liquid reactions are poorly explored in the context of nanomaterials synthesis, despite evidence of significant effects of dissolved gas on nanoparticle properties. This applies to the aqueous synthesis of iron oxide nanoparticles, where gaseous reactants can influence reaction rate, particle size and crystal structure. Conventional batch reactors offer poor control of gas–liquid mass transfer due to lack of control on the gas–liquid interface and are often unsafe when used at high pressure. This work describes the design of a modular flow platform for the water-based synthesis of iron oxide nanoparticles through the oxidative hydrolysis of Fe2+ salts, targeting magnetic hyperthermia applications. Four different reactor systems were designed through the assembly of two modular units, allowing control over the type of gas dissolved in the solution, as well as the flow pattern within the reactor (single-phase and liquid–liquid two-phase flow). The two modular units consisted of a coiled millireactor and a tube-in-tube gas–liquid contactor. The straightforward pressurization of the system allows control over the concentration of gas dissolved in the reactive solution and the ability to operate the reactor at a temperature above the solvent boiling point. The variables controlled in the flow system (temperature, flow pattern and dissolved gaseous reactants) allowed full conversion of the iron precursor to magnetite/maghemite nanocrystals in just 3 min, as compared to several hours normally employed in batch. The single-phase configuration of the flow platform allowed the synthesis of particles with sizes between 26.5 nm (in the presence of carbon monoxide) and 34 nm. On the other hand, the liquid–liquid two-phase flow reactor showed possible evidence of interfacial absorption, leading to particles with different morphology compared to their batch counterpart. When exposed to an alternating magnetic field, the particles produced by the four flow systems showed ILP (intrinsic loss parameter) values between 1.2 and 2.7 nHm2/kg. Scale up by a factor of 5 of one of the configurations was also demonstrated. The scaled-up system led to the synthesis of nanoparticles of equivalent quality to those produced with the small-scale reactor system. The equivalence between the two systems is supported by a simple analysis of the transport phenomena in the small and large-scale setup

PSYCHOSOMATIC DISORDERS IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Objective: to study the psychological status of patients and disabled persons with chronic kidney disease. Materials and methods: 74 patients, invalids because of renal pathology, were included in the study. Psycho-diagnostic data were analyzed by parametric methods (Teilor’s and Spielberger’s tests, intellectual methods). Results: the majority of studied patients with chronic kidney disease (62%) had emotional and motivation disorders, in 38% of them the signs of asthenic state were observed in the clinical picture of psychologic disorders. Intensity of depression and anxiety symptoms significantly increased with the increase of chronic kidney disease severity (p<0.05 and p<0.01, respectively). Conclusions: emotional and motivation disorders were detected in more than a half of patients with chronic kidney disease (62%), and 38% of patients showed the signs of asthenic state manifested by the decrease of functional abilities in performing daily living activities

Self-seeded coprecipitation flow synthesis of iron oxide nanoparticles via triphasic reactor platform: Optimising heating performance under alternating magnetic fields

Liquid-liquid segmentation is a common method to prevent reactor fouling when synthesising nanoparticles in flow, despite limiting synthetic protocols to single reagent addition steps before segmentation. This work demonstrates how a modular triphasic (gas–liquid–liquid) flow reactor platform overcomes this limitation, facilitating a continuous and fouling-free four-step co-precipitation flow synthesis of iron oxide nanoparticles (IONPs) for magnetically induced hyperthermia cancer treatment (MHCT). For this and other biomedical applications water-based IONP syntheses such as co-precipitation are favoured, but producing IONPs > 10 nm as needed for MHCT remains challenging. To overcome this size barrier for co-precipitation syntheses, a seeded growth co-precipitation strategy was employed here for the first time. After demonstrating the synthesis in batch, a triphasic flow reactor was developed to translate the multistep batch protocol into flow. Nitrogen gas was used to space the liquid–liquid segmented slugs evenly, enabling self-synchronised solution addition into the aqueous slugs dispersed in heptane. Three additions of the iron precursor solution followed by citric acid solution addition formed the seeds, grew them to larger IONPs and stabilised them. The flow platform was used for screening of the synthetic parameters to optimise the IONP heating performance in an alternating magnetic field, hence investigating their potential as MHCT heating agents. The optimal reactor settings identified made it possible to continuously synthesise 0.46 gIONPs/h colloidally stable IONPs in the aqueous phase of size ∼15 nm. The fouling-free flow reactor operated at short overall residence times (<5 min) using just ferric and ferrous salts, sodium carbonate and citric acid. The IONPs exhibited high heating performance, with an intrinsic loss power up to 3.76 nH m2 kgFe-1

Investigation of surface structure, electrokinetic and stability properties of highly dispersed Ho₂O₃-Yb₂O₃/SiO₂ nanocomposites

A series of highly dispersed Ho2O3–Yb2O3/SiO2 nanocomposites was synthesized using a liquid-phase method and examined using Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), nitrogen adsorption–desorption, transmission electron microscopy (TEM), Scanning Electron Microscopy (SEM), and photon correlation spectroscopy (PCS). X-ray fluorescence spectrometry (XRF) confirmed a similar amount of weight percentage of Ho, Yb and Si oxides in the prepared samples. Samples HoYbSi1 (Ho2O3:Yb2O3:SiO2 = 0.5:10:89.5, wt. %), HoYbSi2 (Ho2O3:Yb2O3:SiO2 = 1:10:89, wt. %) and HoYbSi3 (Ho2O3:Yb2O3:SiO2 = 2:10:88, wt. %) calcined at 550 °C are amorphous. TEM and SEM analysis confirm a sphere-like morphology with a quite homogeneous size and shape. As compared with the initial silica, the agglomerated particles of nanocomposites in the aqueous medium are in the range from 200 to 850 nm according to PCS data. The effect of anionic polyacrylic acid (PAA) adsorption on fumed silica (SiO2) and Ho2O3–Yb2O3/SiO2 nanocomposite surfaces on suspension stability was studied. The turbidymetry method was used to monitor the initial silica and triple nanooxides suspensions stability as a function of time

Small iron oxide nanoparticles as MRI T1 contrast agent: scalable inexpensive water-based synthesis using a flow reactor

Small iron oxide nanoparticles (IONPs) were synthesised in water via co-precipitation by quenching particle growth after the desired magnetic iron oxide phase formed. This was achieved in a millifluidic multistage flow reactor by precisely timed addition of an acidic solution. IONPs (≤5 nm), a suitable size for positive T1 magnetic resonance imaging (MRI) contrast agents, were obtained and stabilised continuously. This novel flow chemistry approach facilitates a reproducible and scalable production, which is a crucial paradigm shift to utilise IONPs as contrast agents and replace currently used Gd complexes. Acid addition had to be timed carefully, as the inverse spinel structure formed within seconds after initiating the co-precipitation. Late quenching allowed IONPs to grow larger than 5 nm, whereas premature acid addition yielded undesired oxide phases. Use of a flow reactor was not only essential for scalability, but also to synthesise monodisperse and non-agglomerated small IONPs as (i) co-precipitation and acid addition occurred at homogenous environment due to accurate temperature control and rapid mixing and (ii) quenching of particle growth was possible at the optimum time, i.e., a few seconds after initiating co-precipitation. In addition to the timing of growth quenching, the effect of temperature and dextran present during co-precipitation on the final particle size was investigated. This approach differs from small IONP syntheses in batch utilising either growth inhibitors (which likely leads to impurities) or high temperature methods in organic solvents. Furthermore, this continuous synthesis enables the low-cost (<£10 per g) and large-scale production of highly stable small IONPs without the use of toxic reagents. The flow-synthesised small IONPs showed high T1 contrast enhancement, with transversal relaxivity (r2) reduced to 20.5 mM−1 s−1 and longitudinal relaxivity (r1) higher than 10 mM−1 s−1, which is among the highest values reported for water-based IONP synthesis

Some Structural and Chemical Changes in Endocardial Endothelium of Rats in Emotional and Pain Stress Complicated by Hypercholesterolemia

The objective of the research was to study the content of some neutral lipids of endocardial endothelium in rats in relation to structural changes occurring in it, in the co-existence of emotional and pain stress, as well as alimentary hypercholesterolemia. Materials and methods. The electric-impulse model was used for stress modeling. Alimentary hypercholesterolemia was modeled feeding animals an atherogenic diet. The concentration of triacylglycerols, free and esterified cholesterol were examined using the method of thin-layer chromatography performed on silica gel. The concentration of free fatty acids was determined using the radiochemical method. The state of endocardial endothelium was studied with the help of light microscopy; the impression smears obtained from macro preparations of ventricle were analyzed.Results. In co-existence of stress and hypercholesterolemia, significant increase in free cholesterol as well as free fatty acid concentration was noticed. This essentially exceeded the analogical indices under the action of stress only. Structural changes in the endocardium followed by desquamation of separate endotheliocytes were the result of stress reaction. In the action of both pathogenic factors, this process was intensified; layer-by-layer exfoliation of endotheliocytes was observed. Conclusions. In acute emotional and pain stress, changes in lipid spectrum of membrane structures of endocardial endotheliocytes the main manifestation of which is the accumulation of free cholesterol in cells and increase in the levels of free fatty acids take place. The increase in the number of desquamated endothelial cells is the result of stress action as well. Alimentary hypercholesterolemia significantly increases such pathological changes. 

Stable Iron Oxide Nanoflowers with Exceptional Magnetic Heating Efficiency: Simple and Fast Polyol Synthesis

Magnetically induced hyperthermia has reached a milestone in medical nanoscience and in phase III clinical trials for cancer treatment. As it relies on the heat generated by magnetic nanoparticles (NPs) when exposed to an external alternating magnetic field, the heating ability of these NPs is of paramount importance, so is their synthesis. We present a simple and fast method to produce iron oxide nanostructures with excellent heating ability that are colloidally stable in water. A polyol process yielded biocompatible single core nanoparticles and nanoflowers. The effect of parameters such as the precursor concentration, polyol molecular weight as well as reaction time was studied, aiming to produce NPs with the highest possible heating rates. Polyacrylic acid facilitated the formation of excellent nanoheating agents iron oxide nanoflowers (IONFs) within 30 min. The progressive increase of the size of the NFs through applying a seeded growth approach resulted in outstanding enhancement of their heating efficiency with intrinsic loss parameter up to 8.49 nH m2 kgFe-1. The colloidal stability of the NFs was maintained when transferring to an aqueous solution via a simple ligand exchange protocol, replacing polyol ligands with biocompatible sodium tripolyphosphate to secure the IONPs long-term colloidal stabilization

In vitro effect of hyperthermic Ag and Au Fe₃O₄ nanoparticles in cancer cells

PURPOSE: To investigate the anti-cancer efficacy of hyperthermic Ag and Au Fe3O4 core nanoparticles via cytotoxicity study (MTT assay) and the underlying molecular mechanism of action (changes in gene expression via quantitive real time PCR (qRT-PCR). METHODS: HEK293, HCT116, 4T1 and HUH7 human cell lines and 4T1 musculus mammary gland cell line were incubated with Fe3O4 core Ag(Au) shell nanoparticles (NPs) prior to a hyperthermia session. MTT assay was performed to estimate the cytotoxic effects of these NPs. RNA extraction and cDNA synthesis followed so as to quantify mRNA fold change of hsp-70, p53, bcl-2 and casp-3 via qRT-PCR. RESULTS: Fe3O4 core Au shell (concentrations of 400 and 600μg/mL) produced the greatest reduction of viability on HCT116 and 4T1 cells while Fe3O4 core Ag shell (200, 400 and 600μg/mL) reduce viability on HUH7 cells. Hsp-70, p53 and casp-3 were up-regulated while bcl-2 was downregulated in most cases. CONCLUSIONS: Fe3O4 core Ag (Au) shell induced apoptosis on cancer cells (HCT116 and HUH7) via the p53/bcl-2/casp-3 pathway. 4T1 cells also underwent apoptosis via a p53-independent pathway

ОЦІНКА ЕФЕКТИВНОСТІ РЕАБІЛІТАЦІЙНИХ ЗАХОДІВ УЧАСНИКАМ АНТИТЕРОРИСТИЧНОЇ ОПЕРАЦІЇ, ЯКІ ОТРИМАЛИ ЧЕРЕПНО-МОЗКОВУ ТРАВМУ

The article is devoted to the study of the status of patients with the effects of craniocerebral traumas obtained in the ATO zone, at the stages of medical and social rehabilitation.Purpose: determination of the effectiveness of rehabilitation measures taken by ATO participants who have received a craniocerebral trauma, depending on the class of functional disorders.Materials and Methods. We examined 62 patients who were in the clinic of the Research Institute of the Disabled Rehabilitation and had the consequences of mine explosions, close craniocerebral concussion of the brain. Patients were provided with a comprehensive clinical and neuropsychological examination, magnetic resonance imaging or spiral computer tomography, transcranial dopplerography. The severity of neurological disorders was assessed on the NIHSS scale; limitations of life were estimated using the Bartel index.Results. According to the results of the integration assessment of the life limitation of patients we receivedConclusions. The results of the study showed that the factors of the effectiveness of medical and social rehabilitation of patients with a history of craniocerebral injury may be factors such as the dynamics of the reversal of clinical syndromes, the daily life and the ability to work.Стаття присвячена дослідженням визначення стану пацієнтів з наслідками черепно-мозкових травм, отриманих в зоні АТО, на етапах медико-соціальної реабілітації.Мета дослідження. Визначення ефективності реабілітаційних заходів, проведених учасникам АТО, які отримали черепно-мозкову травму, в залежності від класу функціональних розладів.Матеріали та методи. Обстежено 62 пацієнти, які знаходились в клініці Науково-дослідного інституту реабілітації інвалідів (НДІ РІ) і мали наслідки мінно-вибухових травм, ЗЧМТ, струсу головного мозку. Пацієнтам було проведено всебічне клінічне та нейропсихологічне обстеження, МРТ або СКТ, транскраніальну допплерографію. Вираженість неврологічних розладів оцінювали за шкалою NIHSS; обмеження життєдіяльності оцінювали за допомогою індексу Бартеля.Результати. За результатами інтеграційної оцінки обмеження життєдіяльності пацієнтів ми отримали 4 функціональні групи, які відрізнялись між собою за наявністю та ступенем важкості неврологічних ознак хвороби, психологічних розладів та супутніх захворювань, що ускладнюють проведення реабілітаційних заходів.Висновки. Результати дослідження показали, що критеріями ефективності медико-соціальної реабілітації пацієнтів, що мають в анамнезі ЧМТ, можуть бути такі чинники, як динаміка зворотного розвитку клінічних синдромів, повсякденна життєдіяльність та спроможність до трудової діяльності

Development of an in-line magnetometer for flow chemistry and its demonstration for magnetic nanoparticle synthesis

Despite the wide usage of magnetic nanoparticles, it remains challenging to synthesise particles with properties that exploit each application's full potential. Time consuming experimental procedures and particle analysis hinder process development, which is commonly constrained to a handful of experiments without considering particle formation kinetics, reproducibility and scalability. Flow reactors are known for their potential of large-scale production and high-throughput screening of process parameters. These advantages, however, have not been utilised for magnetic nanoparticle synthesis where particle characterisation is performed, with a few exceptions, post-synthesis. To overcome this bottleneck, we developed a highly sensitive magnetometer for flow reactors to characterise magnetic nanoparticles in solution in-line and in real-time using alternating current susceptometry. This flow magnetometer enriches the flow-chemistry toolbox by facilitating continuous quality control and high-throughput screening of magnetic nanoparticle syntheses. The sensitivity required to monitor magnetic nanoparticle syntheses at the typically low concentrations (<100 mM of Fe) was achieved by comparing the signals induced in the sample and reference cell, each of which contained near-identical pairs of induction and pick-up coils. The reference cell was filled only with air, whereas the sample cell was a flow cell allowing sample solution to pass through. Balancing the flow and reference cell impedance with a newly developed electronic circuit was pivotal for the magnetometer's sensitivity. To showcase its potential, the flow magnetometer was used to monitor two iron oxide nanoparticle syntheses with well-known particle formation kinetics, i.e., co-precipitation syntheses with sodium carbonate and sodium hydroxide as base, which have been previously studied via synchrotron X-ray diffraction. The flow magnetometer facilitated batch (on-line) and flow (in-line) synthesis monitoring, providing new insights into the particle formation kinetics as well as, effect of temperature and pH. The compact lab-scale flow device presented here, opens up new possibilities for magnetic nanoparticle synthesis and manufacturing, including 1) early stage reaction characterisation 2) process monitoring and control and 3) high-throughput screening in combination with flow reactors