Soluble Impurities Research Articles

Biopharmaceutical manufacturing processes in which the product of interest is extracellularly expressed typically employ a clarification step following cell culture or fermentation. During clarification, crude cell culture fluid or fermentation broth is processed to remove insoluble solids, cells, debris, and other particulates, with the extracellular product of interest retained in the filtrate. Soluble impurities, such as host cell proteins (HCPs), may also be partially removed. Historically, the clarification process has been considered a limited contributor to Critical Quality Attributes (CQA). As part of upstream harvest, many biopharmaceutical companies have not fully developed quality control strategies from process development to manufacturing, complicating the application of Quality by Design (QbD) principles to this step. However, advancements in upstream and downstream processing (DSP) technologies, alongside increasing cell counts and titers, necessitate reevaluating clarification as a critical process contributing to drug product quality. Conducting controlled studies to define the process and establish parameters using QbD principles can improve control over process impurities and facilitate a logical quality control strategy, integrating quality into the process. This article describes a systematic approach to QbD for a harvest clarification process where the product of interest is extracellular and impurities are removed in the filtrate post-clarification. It highlights methods for optimizing the clarification unit operation using QbD principles, ensuring better process efficiency, and product quality.

The article presents the research results on obtaining the highly effective complex fertilizer sulfoammophos based on wet-pprocess phosphoric acid of various concentrations. This product is not produced in Kazakhstan; to launch it at the Mineral Fertilizers Plant, it is necessary to study the effect of acid concentration and soluble impurity content on obtained fertilizer composition. Standard chemical and instrumental methods of analysis were used to identify the obtained salts. It was found that when evaporating wet-pprocess phosphoric acid in precipitator presence the fluorine content decreases several times. The most intensive reduction in content of other impurities in the acid occurs with soda ash introduction due to their binding in the form of insoluble precipitates of sodium silica fluoride and isomorphic complex compounds of aluminum, iron and calcium. By ammonization of defluorinated wet-pprocess phosphoric acid solutions of concentrations of 25-31% P2O5, sulfoammophos samples were obtained that meet the standard requirements in terms of sulfur and nitrogen content, and even exceed the standard values in terms of phosphorus. The effect of wet-pprocess phosphoric acid concentration on the crystal size and moisture content of sulfoammophos was studied; the optimal acid concentration for obtaining a high-quality product was determined. Sulfoammophos obtained on the basis of evaporated wet-pprocess phosphoric acid of concentration of 25-26% P2O5 is ballast-free concentrated water-soluble complex NP(S) fertilizer.

Abstract. Measuring aerosol-related impurities in ice cores gives insight into Earth's past climate conditions. In order to resolve highly thinned layers and to investigate post-depositional processes, such measurements require high-resolution analysis, especially in deep ice. Micron-resolution impurity data can be collected using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), but this requires careful assessment to avoid misinterpretation. Two-dimensional (2D) imaging with LA-ICP-MS has provided significant new insight, often showing an association between soluble impurities and the ice crystal matrix, but interpreting one-dimensional (1D) signals collected with LA-ICP-MS remains challenging partially due to this impurity–boundary association manifesting strongly in measured signals. In this work, a computational framework has been developed, integrating insights from 2D imaging to aid the interpretation of 1D signals. The framework utilises a simulated model of a macroscopic ice volume with a representative microstructure and soluble impurity localisation that statistically represents distributions seen in 2D maps, allowing quantitative assessment of the imprint of the ice matrix on 1D signals collected from the volume. Input data were collected from four ice core samples from Greenland and Antarctica. For the samples measured, quantifying the variability in 1D signals due to the impurity–matrix imprint shows that modelled continuous bulk signal intensity at the centimetre scale varies below 2 % away from an idealised measurement that captures all variability. In contrast, modelled single-profile micron-resolution LA-ICP-MS signals can vary by an average of more than 100 %. Combining individual LA-ICP-MS signals into smoothed and spatially averaged signals can reduce this variation to between 1.5 and 5.9 %. This approach guides collecting layer-representative signals from LA-ICP-MS line profiles and may help to bridge the scale gap between LA-ICP-MS data and data collected from meltwater analysis.

Background: Extracellular vesicles (EVs), including exosomes, are promising pharmaceutical modalities. They are purified from cell culture supernatant; however, the preparation may contain EVs with the desired therapeutic effects and different types of EVs, lipoproteins, and soluble proteins. Evaluating the composition of particulate impurities and the levels of protein impurities in final preparations is critical for quality control. However, few analytical methods can detect these impurities. Methods: We established and evaluated an analytical method using size-exclusion chromatography-multi-angle light scattering (SEC-MALS) for particle and protein impurity analyses of EV samples. Results: In the particle size distribution analysis of EV samples, SEC-MALS showed higher resolution compared with nanoparticle tracking analysis (NTA) and dynamic light scattering (DLS). MALS showed comparable accuracy and precision to that of other methods for particle size evaluation using polystyrene standard beads with 60, 100, or 200 nm diameter. Coupling SEC-MALS with UV detection quantitatively evaluated soluble protein impurities. Proteomic analysis on the SEC-MALS-fractionated samples identified different EV and lipoprotein marker proteins in different fractions. Conclusions: SEC-MALS can characterize EV preparations obtained from human adipose-derived mesenchymal stem cells, suggesting that it can evaluate the particle component composition in various EV samples and therapeutic exosome preparations.

Due to their distinctive electronic and optical characteristics, transition metal dichalcogenides (TMDs) have become significant materials in optoelectronics. Molybdenum disulfide (MoS2) flakes have received significant interest due to their potential applications. The unique bandgap properties exhibited by MoS2 flakes render them highly appealing for applications in optoelectronic devices [1]. A direct bandgap in this material enables effective interactions between light and matter, which is significant for various applications, including transistors, photodetectors, and light-emitting diodes [2].In this work, we synthesized our MoS2 flakes by exfoliating MoS2 powder following [3]’s recipe. We disperse 500 mg of MoS2 powder into 50 mL of N-Methyl-2-pyrrolidone (NMP)and then use a probe sonicator for the exfoliation process that runs continuously for 6 hours while keeping the sample cooled by a 0 °C ice bath. We later centrifuged at 1500 rpm for 60 min to remove any unexfoliated particles and then centrifuged again at 7500 rpm for 30 min to remove soluble impurities. After removing NMP, the acquired MoS2 flakes dispersed in 50 mL isopropyl alcohol. To study the optical properties of these MoS2 flakes, we prepared 3 x 3 cm2 fused silica substrate rinsed with acetone and DI water, respectively. Before deposition, we sonicate our MoS2 solution for 60 minutes in a bath sonicator. A precise pipet is used to drop-cast 20 uL of MoS2 on the fused silica substrate and wait 120 seconds to let it spread and settle. Afterward, we spin the sample at a low 150 rpm for 40 seconds, ensuring no spillovers. The sample was then carried to a UV-Vis Lambda 1050 spectrometer tool to measure the transmittance and reflectance of the sample over a range of wavelengths 250 to 1200 nm. Subsequently, we calculated absorbance values from this data. We repeat this on the same sample in steps of 20 uL of MoS2, acquiring spectrometer data for 20 to 200 uL of MoS2 on fused silica. The absorbance data showed a slope increase of absorption around 830 nm wavelength, reaching a peak around 660 nm, and It continues to absorb to 250 nm wavelength of the UV range.Moreover, as we increased the MoS2 amount, the overall absorbance increased. At the same time, reflectance increased; however, the change slowed after 60 uL of MoS2. We suspect that the former is due to the increase in the overall thickness of the deposited material, which increases the chance of photons traversing the material to be absorbed. The latter effect could be attributed to texturing, as these deposited MoS2 flakes do not seem to fall flat and create a uniform film and additional reflection from the MoS2 surface. To study that, we prepared five other 3x3 cm2 MoS2 on silicon (Si) samples with 20-100 uL in steps of 20 uL using the same process described earlier. Looking at the morphology using an optical microscope and SEM images of MoS2 on Si, the images show random settlement of MoS2 flakes, leading to uneven coating and witnessing MoS2 flakes arranged and aggregated into islands similar to results reported by others [4]. Also, we found similar dips in reflectivity as reported by literature due to absorption of A and B excitons[5]. Additionally, we measured the electrical conductivity using a hall measurement system of 100 uL MoS2 sample and found that it exhibited n-type behavior with an average sheet resistance value of 2.91x102 Ω/sq. We aim to investigate further the properties and potential applications of these MoS2 flakes.[1] K. F. Mak, C. Lee, J. Hone, J. Shan, and T. F. Heinz, “Atomically Thin MoS2: A New Direct-Gap Semiconductor,” Phys. Rev. Lett., vol. 105, no. 13, p. 136805, Sep. 2010, doi: 10.1103/PhysRevLett.105.136805.[2] H. J. Jin, C. Park, H. H. Byun, S. H. Park, and S.-Y. Choi, “Electrically Modulated Single/Multicolor High Responsivity 2D MoTe2/MoS2 Photodetector for Broadband Detection,” ACS Photonics, vol. 10, no. 9, pp. 3027–3034, Sep. 2023, doi: 10.1021/acsphotonics.3c00143.[3] X. Yu et al., “Hybrid Heterojunctions of Solution-Processed Semiconducting 2D Transition Metal Dichalcogenides,” ACS Energy Lett., vol. 2, no. 2, pp. 524–531, Feb. 2017, doi: 10.1021/acsenergylett.6b00707.[4] N. Zebardastan et al., “2D MoS2 Heterostructures on Epitaxial and Self-Standing Graphene for Energy Storage: From Growth Mechanism to Application,” Advanced Materials Technologies, vol. 7, no. 4, p. 2100963, 2022, doi: 10.1002/admt.202100963.[5] “Layer-number dependent reflection spectra of MoS2 flakes on SiO2/Si substrate.” Accessed: Nov. 23, 2023. [Online]. Available: https://opg-optica-org.libconnect.ku.ac.ae/ome/fulltext.cfm?uri=ome-8-10-3082&id=398132 Figure 1

Salt removal from coal flotation product filter cakes using counter-current and displacement washing

Effect of phosphorus impurities on sulfoaluminate cement-modified gypsum-based self-leveling mortar and improvement method

An integrated airlift loop reactor for continuous production of calcium carbonate from phosphogypsum using a one-step method

Analysis of the wind waves dispersion relation becomes complicated if drift current is present. In general, this relation is derived from the Rayleigh equation, which does not have an analytical solution for an arbitrary velocity profile. In the limiting case, when the gravity-capillary wavelength is small compared to the typical flow depth, the simple Doppler approximation can be used. But in general, this approximation is not valid, and it necessary to take into account the vertical profile of horizontal velocity up to the depth, which corresponds to the considered wavelength. The velocity profile of the drift current is determined using Particle Image Velocimetry. High-resolution spatiotemporal spectra of the waves are obtained with color schlieren technique. Small addition of sodium dodecyl sulfate enabled us to estimate the influence of soluble impurities on the structure of the drift current and modification of the ratio between the drift current depth and the gravity-capillary wavelength. In the present work, an algorithm for numerical calculation of the dispersion relation for a given velocity profile is proposed. It is shown that the dispersion relation for a wind channel is adequately described by Rayleigh equation and the angle between the wave propagation direction and the wind, which is introduced in geophysics for correction of the dispersion relation, may be actually related to different values of the ratio between the wavelength and the drift current depth.

Retardation mechanism of phosphogypsum in phosphogypsum-based excess-sulfate cement

In modern conditions, ensuring the reliability and safety of water supply systems is a primary task for the industrial economy and the safety of life of the population of Ukraine. Constant bombing and damage to critical infrastructure facilities, including water management facilities, endangers the stability and quality of the country's water resources. In this context, conducting research on the identification of man-made risks in water treatment systems using various technologies, as well as developing strategies to increase the reliability and safety of operation of water supply systems are becoming relevant for the industrial sector of Ukraine. In order to increase the reliability of water treatment units and their operational safety, man-made risks were investigated when using ion exchange, electrodialysis, and water distillation technologies at thermal power plants. It is shown that during normal operation of the ion-exchange water purification system with an average productivity of 400 m3/h, in the case of frequent changes in the concentration of salts at the inlet, the risk of receiving underpurified water is 0.0783. This value must be taken into account for the assessment of economic and social-ecological risks, since it exceeds the generally accepted value of 0.01. When using electrodialysis water purification and frequent changes in the concentration of salts at the inlet, the risk of receiving underpurified water is 0.0271. This value is also greater than 0.01 risk accepted as acceptable. The water distillation technology has enough margin to compensate for any deviations in the purification process and gives a very low risk. However, the distillation process is more effective in removing only soluble impurities, while in the case of suspended substances, in particular of organic origin, there is a risk of exceeding the limit of 0.01.

Abstract. The grain size of polycrystalline ice affects key parameters related to the dynamics of ice masses, such as the rheological and dielectric properties of terrestrial ice as well as the ice shells of icy satellites. To investigate the effect of soluble impurities on the grain-growth kinetics of polycrystalline ice, we conducted annealing experiments on polycrystalline ice samples doped with different concentrations of KCl (10−2, 10−3, 10−4 and 10−5 mol L−1) or MgSO4 (10−2 and 10−5 mol L−1). Samples were annealed for a maximum of 100 h at a hydrostatic confining pressure of 20 MPa (corresponding to a depth of about 2 km) and different constant temperatures of 268, 263, 258 and 253 K (corresponding to −5, −10, −15 and −20 °C, respectively). After each experiment, images of a polished sample surface were obtained using an optical microscope equipped with a cold stage. With grain boundaries detected, grains were reconstructed from the images, and an average grain size was determined for each sample. Normal grain growth occurred in all samples. Grain-size data are interpreted using the following grain-growth model: dn-d0n=kt (d: grain size; d0: starting grain size; n: grain-growth exponent; k: growth constant; t: duration). Values of the best-fit grain-growth exponent, n, for all samples range from 2.6 to 6.2, with an average value of 4.7. Pure ice exhibits 3.1 ⩽n⩽ 4.6, with an average value of 3.8. Above the eutectic point, soluble impurities enhance grain growth, as a melt phase is formed, and it could provide a fast diffusion pathway. Below the eutectic point, soluble impurities impede grain growth probably via the formation of salt hydrates that could pin the grain boundaries. Close to the eutectic point, the grain growth of doped ice is similar to pure ice. Natural ice is impure, often containing air bubbles and soluble impurities, and is usually subjected to a hydrostatic pressure. Our data set will provide new insights into the evolution of grain size within and the dynamics of natural ice masses.

Global warming has caused widespread surface lowering of mountain glaciers. By comparing two firn cores collected in 2018 and 2020 from Corbassière glacier in Switzerland, we demonstrate how vulnerable these precious archives of past environmental conditions have become. Within two years, the soluble impurity records were destroyed by melting. The glacier is now irrevocably lost as an archive for reconstructing major atmospheric aerosol components.

A systematic study on the mechano-thermic reduction of low-grade ilmenite concentrate for the production of high-grade TiO2 powder used in the production of non-oxide ceramics for cutting tool applications has been successfully carried out. Samples were prepared via planetary ball milling and carbothermic reduction processes, and the as-reduced product was subsequently leached in order to improve the synthesized TiO2 by removing the metallic iron in it and other minor soluble impurities dissolved in the iron. The mechano-thermic reduction was achieved by milling a representative mixture of ilmenite and carbon in a molar ratio of 1:1, followed by carbothermic reduction at 1000 °C in a laboratory high-temperature furnace for 60 min. The as-reduced product was subsequently leached at 80 °C for 6 h in a hydrochloric acid solution. It was found that there was a complete reduction of ilmenite to metallic iron and TiO2 at 1000 °C. The results of the FESEM showed there were only two distinct regions of metallic iron (bright region) and titanium dioxide (grey region) with minor traces of unreacted carbon (dark spots), although there was clear regional demarcation between these regions. However, the iron dissolution during the acid treatment was almost 100% as there were no peaks of iron in the as-leached powder. The results of these analyses confirmed the synthesis of high-grade TiO2, which finds application in cutting tool applications and other areas such as in reflective pigment production.

Industries are required to utilize treatment technologies to reduce contaminants in wastewater prior to discharge and to valorize by-products to increase sustainability and competitiveness. Most acid leaching gypsum purification studies have obviated the treatment of the highly acidic wastewater produced. In this work, acidic wastewater from acid leaching purification of post-consumer gypsum was treated to recover a valuable solid product and reusable water. The main aims of this work were to determine the impact of recirculating acidic and treated wastewaters on the efficiency of the acid leaching purification process and to valorize the impurities in the wastewater. Samples were characterized through X-ray fluorescence and X-ray diffraction. SimaPro 9.5 and the ReCiPe 2016 midpoint method were used for the life cycle assessment of three sustainable wastewater management approaches. The reuse of the acidic wastewater did not improve the chemical purity of gypsum. Soluble impurities were precipitated at pH 10.5 as a magnesium-rich gypsum that could be commercialized as fertilizer or soil ameliorant. The alkaline-treated water was reused for six acid leaching purification cycles without impacting the efficiency of the purification process. An acid leaching–neutralization–filtration–precipitation approach demonstrated superior overall environmental performance. Barriers and enabling measures for the implementation of an in-house wastewater treatment were identified.

The isolation and enrichment of specific extracellular vesicle (EV) subpopulations are essential in the context of precision medicine. However, the current methods predominantly rely on a single-positive marker and are susceptible to interference from soluble proteins or impurities. This limitation represents a significant obstacle to the widespread application of EVs in biological research. Herein, a novel approach that utilizes proximity ligation assay (PLA) and DNA-RNA hybridization are proposed to facilitate the binding of two proteins on the EV membrane in advance enabling the isolation and enrichment of intact EVs with double-positive membrane proteins followed by using functionalized magnetic beads for capture and enzymatic cleavage for isolated EVs release. The isolated subpopulations of EVs can be further utilized for cellular uptake studies, high-throughput small RNA sequencing, and breast cancer diagnosis. Hence, developing and implementing a specialized system for isolating and enriching a specific subpopulation of EVs can enhance basic and clinical research in this field.

Anti-solvent engineering to rapid purify PbI2 for efficient perovskite solar cells

Highly sensitive quantitative detection of glycans on exosomes in renal disease serums using fluorescence signal amplification strategies

Downstream process intensification for biotechnologically generated hyaluronic acid: Purification and characterization

Ensuring uninterrupted and reliable operation of water treatment systems is a priority task of the industrial complex of Ukraine. For effective reliability management in water treatment systems, it is necessary to analyze potential failures and determine the probability of their occurrence. For the purpose of research to determine the probability of the occurrence of risks as a result of failures of various units of the water purification system, using the example of the operation of a column-type electrocoagulator, it is proposed to use the structural and functional block diagram of water purification systems to obtain generalized patterns, which makes it possible to reduce the entire system to several interdependent units, namely: 1) fine-cleaning filtration unit; 2) a unit for cleaning from soluble impurities; 3) a unit for cleaning coarse impurities; 4) pipe-pump unit. When the water treatment system is operating, taking into account the ranking of the reliability of the units, it can be stated that the 1st unit may fail at the beginning, followed by the 2nd, 3rd and 4th units. It is established that if all the units of the system are working, the system is in the S0 state. When other blocks fail, in the same sequence, the system will be in states S1, S2, S3 and S4. The most interesting are the states of the system, in which block failures do not cause shutdown of the entire system, but only its off-duty operation, which is manifested only as a result of the deterioration of the quality of treated water. Analyzing the obtained results, it can be asserted that during the operation of the water treatment system, the highest probability of failure is in unit 1. After the unit is restored and during further operation of the system, the highest probability of failure is unit 2, then unit 4 and unit 3. The failure probabilities of the units are the probabilities of risks, moreover, the physical value generated by these risks (the amount of polluted water that entered the ecosystem or the boiler unit) will be greater, the longer the unit failure detection period. When the water treatment system operates for a long enough time, a probabilistic constant mode of transition from state to state is established in it according to the scheme «working state of all blocks - failure of one or several blocks - repair - working state of all blocks». The probability of the sequence and duration of these events can be determined, which makes it possible, on the one hand, to assess the risks arising during operation and to determine a management strategy to minimize these risks.