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ABSTRACT Polystyrene spheres ranging in diameter from 2, 5, 10, to 20 μm were embedded in five different types of thick organic films (> 50 μm) to serve as model systems to evaluate the use of time‐of‐flight secondary ion mass spectrometry for the localization and particle sizing of pharmaceuticals in orodispersible drug delivery films. It was found that certain films, such as gelatin and ethyl cellulose, are prone to developing micron‐scale topography which can affect the linearity of the sputter yield, which can ultimately affect the maximum analyzable depth. Surprisingly, the sputter yield of the film was more of a determining factor for affecting the measurement of spheres. It was possible to more accurately extract the true dimensions of the buried spheres in faster sputtering films, while slower sputtering films were associated with matrix effects and sputtering artifacts that degraded the quality of the reconstructed image. Signal attenuation was also found to be problematic and quite significant for certain film chemistries, which placed a limit on the size of the particles that could be visualized. Overall, visualization of particles embedded in thick organic films is possible, but the extraction of quantitative data such as size and the amount of material is difficult given the influence of sample dependent sputtering artifacts. [ABSTRACT FROM AUTHOR]

Dynamic light scattering (DLS) is a highly efficient approach for extracting particle size distributions (PSDs) from autocorrelation functions (ACFs) to measure nanoparticle particles. However, it is a technical challenge to get an exact inversion of the PSD in DLS. Generally, Tikhonov regularization is widely used to address this issue; it uses the L2 norm for both the data fitting term (DFT) and the regularization constraint term. However, the L2 norm's DFT has poor robustness, and its regularization term lacks sparsity, making the solution susceptible to noise and a reduction in accuracy. To solve this problem, the Lp,q norm restrictive model is formulated to examine the impact of various norms in the DFT and regularization term on the inversion results. On this basis, combined with the robustness of DFT and the sparsity of regularization terms, an L1,∞-constrained Tikhonov regularization model was constructed. This model improves the inversion accuracy of PSD and offers a better noise-resistance performance. Simulation tests reveal that the L1,∞ model has strong noise resistance, exceptional inversion precision, and excellent bimodal resolution. The inversion outcomes for the 33 nm unimodal particles, the 55 nm unimodal, and the 33 nm/203 nm bimodal experimental particles show that L1,∞ reduces peak errors by at most 6.06%, 5.46%, and 12.12%/3.94% compared to L2,2, L1,2, and L2,∞ models, respectively. These simulations are validated by experimental data. [ABSTRACT FROM AUTHOR]

Reproducible aerosol generation in combination with stable aerosol properties are essential prerequisites for compliant performance of acute or repeated inhalation toxicity tests of particulate materials according to OECD TG 403, 436, 412, or 413. A frequent problem of powder aerosol generation is the formation of coarse agglomerates with low shear resistance, which are beyond the tolerable size range but not detected by the prescribed aerodynamic measurement techniques by cascade impactor as the measurement conditions cause a disintegration into smaller fragments. But such agglomerates are observed during the transport to the inhalation chambers. These effects particularly apply to high mass concentrations and low-density powders, i.e., pyrogenic oxides. This study describes the transport influence in the airflow on the change of powder aerosols and on their respirability. A simplified short tube set-up was developed for the aerosol transport pre-tests, which allows the determination of the optimal aerosol formation conditions for the inhalation tests. The particles were measured with low shear using laser diffraction measurement or optical particle counters. The calculation of the aerodynamic particle sizes prescribed in the guidelines requires knowledge of the effective particle density of the porous aerosol particles. A practicable method for determining these is presented and described. In the outlook, first low concentration measurements show that clear agglomeration effects can also occur at particle concentrations around 20 mg/m³. • Short tube setup simulates aerosol transport in real inhalation chamber setup. • Low shear optical particle sizing reveals strong re-agglomeration of aerosols. • Pyrogenic aerosol re-agglomeration reduces respirable fraction concentration. • OECD TGs require smaller MMAD sizes than pyrogenic powders can perform. • OECD powder tests are hardly conformable with CLP as placed on the market. [ABSTRACT FROM AUTHOR]

Purpose: A comparative assessment was performed to evaluate the potential of particle sizing by an ensemble based conventional dynamic light scattering (DLS) technique and an emerging technology based on tunable resistive pulse sensing (TRPS) using particle by particle approach by evaluating three different types of vaccine formulations representing three case studies and showing the limitation of each technique, instrument variability, sensitivity, and the resolution in mixed population. Methods: Three types of in-house vaccine formulations- a protein antigen, an outer membrane vesicle and viral particles were simultaneously evaluated by TRPS based Exoid and two DLS instruments-Zetatrac and Zetasizer for particle size distribution, aggregates, and resolution of polydisperse species. Results: The data from first case study show the risk of possible size overestimation and size averaging in polydisperse samples in DLS measurements which can be addressed by the TRPS analysis. It also shows how TRPS may be utilized only to large size antigens due to its limited size range. The second case study highlights the difference in the sensitivities of two DLS instruments working on the same principle. The third case study show that how TRPS can better resolve the large aggregate species compare to DLS in polydisperse samples. Conclusion: This analysis shows that TRPS can be used as an orthogonal technique in addition to conventional DLS based methods for more precise and in-depth characterization. Both techniques are efficient in size characterization and produce comparable results, however the choice will depend on the type of formulation and size range to be evaluated. [ABSTRACT FROM AUTHOR]

Titanium dioxide (TiO2) pigment is a non-toxic, particulate material in widespread use and found in everyone’s daily life. The particle size of the anatase or rutile crystals are optimised to produce a pigment that provides the best possible whiteness and opacity. The average particle size is intentionally much larger than the 100 nm boundary of the EU nanomaterial definition, but the TiO2 pigment manufacturing processes results in a finite nanoscale content fraction. This optically inefficient nanoscale fraction needs to be quantified in line with EU regulations. In this paper, we describe the measurement procedures used for product quality assurance by three TiO2 manufacturing companies and present number-based primary particle size distributions (PSDs) obtained in a round-robin study performed on five anatase pigments fabricated by means of sulfate processes in different plants and commonly used worldwide in food, feed, pharmaceutical and cosmetic applications. The PSDs measured by the three titanium dioxide manufacturers based on electron micrographs are in excellent agreement with one another but differ significantly from those published elsewhere. Importantly, in some cases, the PSDs result in a different regulatory classification for some of the samples tested. The electron microscopy results published here are supported by results from other complementary methods including surface area measurements. It is the intention of this publication to contribute to an ongoing discussion on size measurements of TiO2 pigments and other particulate materials and advance the development of widely acceptable, precise, and reproducible measurement protocols for measuring the number-based PSDs of particulate products in the size range of TiO2 pigments.

Dynamic light scattering (DLS) is a highly efficient approach for extracting particle size distributions (PSDs) from autocorrelation functions (ACFs) to measure nanoparticle particles. However, it is a technical challenge to get an exact inversion of the PSD in DLS. Generally, Tikhonov regularization is widely used to address this issue; it uses the L2 norm for both the data fitting term (DFT) and the regularization constraint term. However, the L2 norm’s DFT has poor robustness, and its regularization term lacks sparsity, making the solution susceptible to noise and a reduction in accuracy. To solve this problem, the Lp,q norm restrictive model is formulated to examine the impact of various norms in the DFT and regularization term on the inversion results. On this basis, combined with the robustness of DFT and the sparsity of regularization terms, an L1,∞-constrained Tikhonov regularization model was constructed. This model improves the inversion accuracy of PSD and offers a better noise-resistance performance. Simulation tests reveal that the L1,∞ model has strong noise resistance, exceptional inversion precision, and excellent bimodal resolution. The inversion outcomes for the 33 nm unimodal particles, the 55 nm unimodal, and the 33 nm/203 nm bimodal experimental particles show that L1,∞ reduces peak errors by at most 6.06%, 5.46%, and 12.12%/3.94% compared to L2,2, L1,2, and L2,∞ models, respectively. These simulations are validated by experimental data.

Chemical mechanical polishing/planarization (CMP) slurry contains mainly abrasive grains (primary particles) with few aggregations (secondary particles). Measuring the particle size distribution (PSD) of CMP slurry is crucial for improving the productivity of the CMP process. For the quality management of CMP slurry, it is necessary to evaluate both the sizes and quantities of both the primary and secondary particles. Conventional PSD analysis methods, except for image analysis, face challenges in identifying primary and secondary particles for PSD measurements. For image analysis, the particles must be transferred from a suspension to a substrate using the conventional sampling method; however, this creates aggregates, resulting in a change in the PSD of the particles on the substrate compared to that in suspension under poly-dispersed conditions. Thus, this study proposed a novel particle sizing method using nanoparticle chip (NPC) to assist in the image analysis of the PSD. The NPC can pick up a single particle in a small volume droplet to avoid aggregation and maintain the poly-dispersed condition of the particles in suspension. The primary and secondary particles can be identified using scanning electron microscope (SEM) or atomic force microscope (AFM), and the PSD can be evaluated by measuring the area and height of the particles. Further, the quantities of both the primary and secondary particles can be counted from the substrate. This study presented a comparison of the diameter measurements using NPC and the conventional method. The results show that the NPC identified the primary and secondary particles and decreased the measurement error of the particle diameters. Consequently, the NPC proves to be superior to the conventional method for use in the PSD analysis of CMP slurry. • Nanoparticle chip (NPC) sizing for CMP slurry particle size distribution (PSD). • NPC avoids particle aggregation, maintains PSD in poly-dispersed suspension. • Primary and secondary particles separated to lower equivalent height diameter error. • PSD of primary particles and number of secondary particles measured using NPC. [ABSTRACT FROM AUTHOR]

Nanocomposites based on silver nanoparticles and chitosan present important advantages for medical applications, showing over time their role in antibacterial evaluation. This work presents the comparative study of two chemical synthesis procedures of nanocomposites, based on trisodium citrate dihydrate and sodium hydroxide, using various chitosan concentrations for a complex investigation. The nanocomposites were characterized by AFM and DLS regarding their dimensions, while FT-IR and UV–VIS spectrometry were used for the optical properties and to reveal the binding of silver nanoparticles with chitosan. Their antibacterial effect was determined using a disk diffusion method on two bacteria strains, E. coli and S. aureus. The results indicate that, when using both methods, the nanocomposites obtained were below 100 nm, yet the antibacterial effect proved to be stronger for the nanocomposites obtained using sodium hydroxide. Furthermore, the antibacterial effect can be related to the nanocomposites' sizes, since the smallest dimension nanocomposites exhibited the best bacterial growth inhibition on both bacteria strains we tested and for both types of silver nanocomposites. [ABSTRACT FROM AUTHOR]

This paper presents the feasibility of Fraunhofer diffraction analysis as a measure of the size of fast‐moving inkjet droplets. This measurement method showed that an inkjet droplet measurement tool was possible with a good balance of real‐time measurement and accuracy. [ABSTRACT FROM AUTHOR]

Abstract There is a critical need to generate environmentally relevant microplastics (MPs) and nanoplastics (NPs) to better investigate their behavior in laboratory settings. Environmental MPs are heterogenous in size and shape, unlike monodisperse and uniform microspheres commonly used as surrogates. Cryogenic grinding, or cryomilling, was successfully utilized to transform polystyrene (PS) bulk material into heterogenous micro and nano fragments. Fourier-Transform Infrared (FTIR) spectroscopy confirmed that this approach did not alter polymer surface chemistry. The number of milling cycles (time of milling) and frequency of grinding (intensity of milling) were varied to investigate the role cryomilling parameters had on generated MP characteristics. The resulting particle size distributions of cryomilled samples were measured and compared. Coulter Counter and Nanoparticle Tracking Analysis (NTA) were used to measure the particle size distributions at the micro and nanoparticle size ranges, respectively. Microspheres were used to determine what camera settings yielded more accurate sizing and to reduce bias in the NTA analysis. Increasing milling cycles generally increased the number of smaller particles. The evolution of the measured size distributions indicated that small nanosized fragments broke off from larger MPs during cryomilling, steadily eroding larger MP fragments. The number of milling cycles was observed to more consistently impact the size distributions of fragments compared to the frequency of milling. This study offers both analysis of the cryomilling process and recommendations for generating more realistic PS MP/NPs for examining environmental fate and effects.

There is a critical need to generate environmentally relevant microplastics (MPs) and nanoplastics (NPs) to better investigate their behavior in laboratory settings. Environmental MPs are heterogenous in size and shape, unlike monodisperse and uniform microspheres commonly used as surrogates. Cryogenic grinding, or cryomilling, was successfully utilized to transform polystyrene (PS) bulk material into heterogenous micro and nano fragments. Fourier-Transform Infrared (FTIR) spectroscopy confirmed that this approach did not alter polymer surface chemistry. The number of milling cycles (time of milling) and frequency of grinding (intensity of milling) were varied to investigate the role cryomilling parameters had on generated MP characteristics. The resulting particle size distributions of cryomilled samples were measured and compared. Coulter Counter and Nanoparticle Tracking Analysis (NTA) were used to measure the particle size distributions at the micro and nanoparticle size ranges, respectively. Microspheres were used to determine what camera settings yielded more accurate sizing and to reduce bias in the NTA analysis. Increasing milling cycles generally increased the number of smaller particles. The evolution of the measured size distributions indicated that small nanosized fragments broke off from larger MPs during cryomilling, steadily eroding larger MP fragments. The number of milling cycles was observed to more consistently impact the size distributions of fragments compared to the frequency of milling. This study offers both analysis of the cryomilling process and recommendations for generating more realistic PS MP/NPs for examining environmental fate and effects. [ABSTRACT FROM AUTHOR]

The size of silver nanoparticles plays a crucial role in their ultimate application in the medical and industrial fields, as their efficacy is enhanced by decreasing dimensions. This study presents two chemical synthesis procedures for obtaining silver particles and compares the results to a commercially available Ag-based product. The first procedure involves laboratory-based chemical reduction using D-glucose (C6H12O6) and NaOH as reducing agents, while the second approach utilizes trisodium citrate dehydrate (C6H5Na3O7·2H2O, TSC). The Ag nanoparticle suspensions were examined using FT-IR and UV-VIS spectroscopy, which indicated the formation of Ag particles. The dimensional properties were investigated using Atomic Force Microscopy (AFM) and confirmed by Dynamic Light Scattering (DLS). The results showed particle size from microparticles to nanoparticles, with a particle size of approximately 60 nm observed for the laboratory-based TSC synthesis approach. [ABSTRACT FROM AUTHOR]

High-solid-content polystyrene and polyvinyl acetate dispersions of polymer particles with a 50 nm to 500 nm mean particle diameter and 12–55% (w/w) solid content have been produced via emulsion polymerization and characterized regarding their optical and physical properties. Both systems have been analyzed with common particle-size-measuring techniques like dynamic light scattering (DLS) and static light scattering (SLS) and compared to inline particle size distribution (PSD) measurements via photon density wave (PDW) spectroscopy in undiluted samples. It is shown that particle size measurements of undiluted polystyrene dispersions are in good agreement between analysis methods. However, for polyvinyl acetate particles, size determination is challenging due to bound water in the produced polymer. For the first time, water-swelling factors were determined via an iterative approach of PDW spectroscopy error (Χ2) minimization. It is shown that water-swollen particles can be analyzed in high-solid-content solutions and their physical properties can be assumed to determine the refractive index, density, and volume fraction in dispersion. It was found that assumed water swelling improved the reduced scattering coefficient fit by PDW spectroscopy by up to ten times and particle size determination was refined and enabled. Particle size analysis of the water-swollen particles agreed well with offline-based state-of-the-art techniques. [ABSTRACT FROM AUTHOR]

[Display omitted] Sub-visible particles (SVPs) in pharmaceutical products are a critical quality attribute, and therefore should be monitored during development. Although light obscuration (LO) and microscopic particle count tests are the primary pharmacopeial methods used to quantify SVPs, flow imaging methods like Micro-Flow Imaging (MFI™) appear to overcome shortcomings of LO such as limited sensitivity concerning smaller translucent SVPs in the size range < 10 µm. Nowadays, MFI™ is routinely utilized during development of biologicals. Oftentimes multiple devices are distributed across several laboratories and departments. This poses challenges in data interpretation and consistency as well as in the use of multiple devices for one purpose. In this study, we systematically evaluated seven MFI™ instruments concerning their counting and size precision and accuracy, using an inter-comparable approach to mimic daily working routine. Therefore, we investigated three different types of particles (i) NIST certified counting standards, (ii) protein-coated particles, and (iii) stress-induced particles from a monoclonal antibody. We compared the results to alternative particle detection methods: LO and Backgrounded Membrane Imaging (BMI). Our results showed that the precision and accuracy of particle count and size, as well as the comparability of instruments, depended on the particle source and its material properties. The various MFI™ instruments investigated showed high precision (<15 %) and data generated on different instruments were of the same order of magnitude within pharmacopeial relevant size ranges for NIST certified counting standards. However, we found limitations in the upper and lower detection limits, contrary to the limits claimed by the manufacturer. In addition, proteinaceous and protein-containing particles showed statistically significant differences in particle counts, while the measured particle diameters of all sizes were quite consistent. [ABSTRACT FROM AUTHOR]

Extracts with emulsifying capacity have been extracted from split peas (Pisum sativum). At pH 7 and extract concentrations above 0.75 g L−1 s, stable emulsions were produced, with droplets of tens μm. At higher concentrations (2 g L−1 s) bridging flocculation occurs, with the flocs breaking up into μm-sized particles upon SDS addition, reaching sizes comparable to those obtained by oilve compost emulsifiers. At even higher concentrations, depletion flocculation is observed due to unadsorbed extracts. The extract cannot emulsify at pH 3. In all cases, the interfacial tension is quickly reduced (at a higher degree at pH 7) due to the fast adsorption of small-molecular surfactants. Within 10 s further reductions are observed, as macromolecules are adsorbed, forming steric layers at the oil – water interface at pH 7. At pH 3 the adsorption of the macromolecules reduces the interfacial tension to a smaller extent, and is followed by a slower (over 100 s) rearrangement at the interface. Coupled with a change in zeta potential from 10.8 ± 0.6 mV at pH 7 down to 4.1 ± 2.2 mV at pH 3, these phenomena render the interfacial layer at pH 3 unable to stabilize against coalescence. Size exclusion chromatography of the extract, the emulsion serum and the cream layer highlight the preferential adsorption of specific biopolymers at the interface and confirm the hypothesis of the sequential adsorption and interfacial rearrangements. Fourier transform infrared spectra show that proteins are preferably adsorbed at the interface, while polysaccharides remain at the bulk phase. [ABSTRACT FROM AUTHOR]

Particle size distributions (PSDs) define the description of particle systems and of their separation processes in mechanical process engineering. Modern analytical methods, in particular image analysis, and their combination with material‐specific analytics record additional geometric and material parameters of particles. Many of these particle properties, like particle size, are not constant but also distributed, leading to a multi‐dimensional particle property distribution that can be used to describe particle processes. Thus, it is possible to define a partition function that quantifies separation in multidimensional space. The multidimensional approaches can be simply reduced in their dimensionality, so that the known one‐dimensional distribution functions, e.g., a PSD, can be obtained as marginal distributions. [ABSTRACT FROM AUTHOR]

The Depth from Defocus (DFD) imaging technique for measuring the size and number concentration of particles in dispersed two-phase flows has up to now been restricted to the processing of spherical particle images. This study examines how this technique can be extended to process irregular particle images, arising either from neighboring spherical particles which lead to overlapping images, or from the imaging of non-spherical particles. In either case, the application scope of the DFD technique is significantly expanded. On the one hand the ability to identify and process overlapping images allows measurements to be performed at higher number/volume concentrations. On the other hand, especially solid particles are often non-spherical, thus making the DFD technique attractive for these applications. For both cases, the processing algorithms are experimentally benchmarked against ground truth using a dedicated apparatus in which particles of known size, shape and degree of overlapping images can be systematically varied. • Size and position of two particles are determined from overlapping blurred images. • The area equivalent size and position of irregularly shaped particles are measured. • DFD technique is improved to measure flows with higher concentrations of particles. [ABSTRACT FROM AUTHOR]

Particle size inversion of dynamic light scattering (DLS) is a typically ill-posed problem. Regularization is an effective method to solve the problem. The regularization involves imposing constraints on the fitted autocorrelation function data by adding a norm. The classical regularization inversion for DLS data is constrained by the L2 norm. In the optimization equation, the norm determines the smoothness and stability of the inversion result, affecting the inversion accuracy. In this paper, the Lp norm regularization model is constructed. When p is 1, 2, 10, 50, 100, 1000, and ∞, respectively, the influence of their norm models on the inversion results of data with different noise levels is studied. The results prove that overall, the inversion distribution errors show a downward trend with the increase of p. When p is larger than 10, there is no significant difference in distribution error. Compared with L2, L∞ can provide better performance for unimodal particles with strong noise, although this does not occur in weak noise cases. Meanwhile, L∞ has lower sensitivity to noise and better peak resolution, and its inverse particle size distribution is closer to the true distribution for bimodal particles. Thus, L∞ is more suitable for the inversion of DLS data. [ABSTRACT FROM AUTHOR]

In the Sulige gas field in Changqing Oilfield, the Liujiagou formation is a low pressure formation, the low density cement slurries presently used in this area have poor pressure resistance; the cement slurries under high pressures will have their density increased and rheology deteriorated. In field operations with these cement slurries, the operation pressures were high, generally causing the cement slurries to be lost into the formations, and the cementing quality is poor because of less cement slurries in the annulus. To solve this problem, a new cement slurry with low friction low density was formulated. This new cement slurry is pressure resistant and has the property of preventing itself from being lost into formations. Using the close packing theory, particles of 4 sizes were selected. A light material with excellent pressure resistance and other appropriate additives were selected to formulate the target cement slurry. The density of the new cement slurry is adjustable between 1.25 g/cm3 and 1.35 g/cm3, the Fanning friction coefficient was reduced by about 50%. The new cement slurry has good pressure resistance and leaking preventive property. Study on the agitation and mixing techniques shows that mechanical agitation and mixing can be used, 99% of the properties of the bulk sample and those of the small sample coincide with each other, ensuring the qualification and efficiency of the cement mixing. In field operations in the Sulige gas field, four wells were cemented with success, no loss of cement slurry has ever happened, and the cementing job was qualified. During the cementing, the operational pressure was significantly reduced, and the job quality was obviously improved. This laboratory study and the field application provide a strong technical support to cementing wells penetrating low pressure formations into which cement slurries are easily lost. [ABSTRACT FROM AUTHOR]

Quantifying the heterogeneous nature of protein aggregates is important to understanding the impact aggregates may have on the performance of antibody therapeutics. The spatially averaged density ρ p of aggregates, defined as the total mass, including water, divided by the volume, is a parameter that can be used to relate size distributions measured by orthogonal methods, to characterize protein particles, and perhaps to estimate the amount of aggregated protein in a sample. We report measurements by two methods on the distribution of density values for different aggregate sizes, where the aggregates were produced by stir-stressing fluorescently labeled monoclonal antibody (NISTmAb). A fluorescence microscope was used to image particles. Each particle was analyzed for brightfield equivalent circular diameter (ECD) and fluorescence intensity and the results converted to average density. Measurements were also obtained using video holography. The aggregates were highly porous with median density decreasing from 1.07 g/cm3 to 1.02 g/cm3 as the size increased from 0.9 μm to 6 μm by fluorescence, and similar results by video holography. The distribution in density for a given particle size was asymmetrical and broad. For example, particles with an ECD of 2.5 μm ranged in density from 1.005 g/cm3 to 1.1 g/cm3. [ABSTRACT FROM AUTHOR]

Dynamic Light Scattering is a well-established technique used in particle sizing. An alternative procedure for Dynamic Light Scattering time series processing based on spectral entropy computation and Artificial Neural Networks is described. An error analysis of the proposed method was carried out and the results on both the simulated and on the experimental DLS time series are presented in detail. The results reveal the possibility of designing an advanced sensor capable of detecting particles with a size bigger than a threshold using this alternative for processing the DLS time series. [ABSTRACT FROM AUTHOR]

Purpose: The goal of this study was to characterize an acellular pertussis vaccine (Tdap) containing genetically modified pertussis toxin (gdPT) and TLR agonist adsorbed to AlOOH adjuvant. Methods: Several analytical tools including nanoDSF, FTIR, and LD were used to examine the conformation of novel gdPT and the composition of AlOOH adjuvant formulations adsorbed to pertussis vaccine. Results: DLS particle size results were 9.3 nm and 320 nm for gdPT. For pertussis toxoid (PT), the DLS particle size results were larger at ~440 nm. After adsorption to AlOOH, which was driven by the protein antigen, the size distribution ranged from 3.5 to 22 µm. Two thermal transitions were observed by DSC for gdPT at 70 °C and 102 °C. The main thermal transition was confirmed to be at 72 °C by nanoDSF. All three vaccine formulations showed one thermal transition: Tdap-AlOOH had a thermal transition of 74.6 °C, Tdap-E6020-AlOOH had a thermal transition at 74.2 °C, and Tdap-CpG-AlOOH had a thermal transition at 77.0 °C. Analysis of pertussis toxin (PTx) and gdPT was also performed by FTIR spectroscopy for the purpose of comparison. The second derivative of the FTIR spectra showed an additional feature for PTx at 1685 cm−1 compared to gdPT. The antigen’s amide I and II regions were largely unchanged after adsorption to AlOOH adjuvant as shown by FTIR, suggesting that there were no significant changes in the secondary structure. Conclusion: gdPT conformation was successfully characterized using an array of analytical methods. All three Tdap formulations have similar thermal stability as shown by nanoDSF, similar size distribution as shown by LD, and similar overall secondary structure as shown by FTIR. In-line particle sizing and IR can be used as in-process characterization tools to monitor consistency of adsorbed vaccine and to confirm product identity.

Single-step trans-vertical moulds used to prepare grain mounts for SEM-automated-mineralogy based instruments have been shown to lead to more representative sample statistics. For samples that contain a variety of mineral phases, denser phases can settle to the bottom of an epoxy mould during the curing phase. Slicing and polishing a cross section through density-stratified moulds of the sample material can compensate for this. Aliquots from offshore drill well cuttings were prepared using three different methods: (1) traditional epoxy mounting, (2) two-step trans-vertical moulds, and (3) single-step trans-vertical moulds. All were analysed with a FEI Quanta 650 FEG instrument using MLA software with similar acquisition parameters. The results indicate that the single-step trans-vertical moulds are reproducible, lead to more accurate statistics, and yield MLA calculated elemental assays that closely match with data from standard analytical methods. In addition, these moulds can be made in half the time of the two-step trans-vertical moulds, and because of the unique geometry of the custom-made SEM holders, the analytical throughput is doubled. Depending on the size fraction of the well cuttings, the throughput can be further increased by slicing off the remaining epoxy to allow for more samples in the 26x TV holder. A unique cell holder was created to accommodate these trans-vertical samples, allowing them to fit into a LA-ICP-MS instrument such that detailed follow-up microanalyses can be conducted on specific minerals. For instance geochronology can be conducted on grains of interest (e.g., zircons), which had been mapped by the SEM-MLA. [ABSTRACT FROM AUTHOR]

[Display omitted] Dynamic Light Scattering (DLS) generated particle size distributions (PSD) of polymer-stabilized nanoparticles are dependent on the optimization parameters used to generate an inversion solution fit to the measured autocorrelation function. The accuracy of the DLS PSD average and polydispersity can be determined by comparing analyzed Transmission Electron Microscopy (TEM) images with the DLS results if the TEM measured sizes can be corrected for the thickness of the hydrated polymer corona that impacts particle hydrodynamics but is a collapsed, desiccated shell in the TEM images. Nanoparticles were prepared by Flash NanoPrecipitation with either poly(ethylene glycol) (PEG) or hydroxypropyl methylcellulose acetate succinate (HPMCAS) stabilizing polymers. Solvated nanoparticle size distributions were measured by DLS in aqueous media. The same nanoparticle dispersions were lyophilized onto TEM grids and stained by ruthenium tetroxide (RuO 4) vapor to improve electron contrast. Desiccated particle size distributions were generated by measuring a minimum of 300 particle diameters in the stained TEM images. Using our protocol for staining soft matter nanoparticles in TEM measurements, we have quantitatively analyzed the correlation between DLS and TEM generated PSDs. Average diameters disagree by the hydrated polymer corona thickness for each stabilizer due to the high-vacuum TEM environment, with 21.4 nm for PEG and 51.2 nm for HPMCAS. While corrected average diameter agrees within 10% for each technique, DLS consistently over-estimates the standard deviation of the PSD by 100% compared to the TEM measurement. [ABSTRACT FROM AUTHOR]

[Display omitted] • Silver nanoparticles (Ag NPs) stabilized by four different capping agents are applied as catalysts of CO 2 reduction in a zero-gap gas-flow electrolyser. • Branched polyethylenimine (BPEI), polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), and citrate are used as capping agents. • Depending on the nature of the capping agent, Ag NPs undergo different degradation pathways. • BPEI is the most effective stabilizer but also blocks CO 2 reduction the most. • Particles capped by PVP tend mostly to corrode (leading to particle shrinkage) while in case of PEG- and citrate-capped particles degradation involves particle size growth. • The statistical analysis of SEM images and WAXS measurements provide an insight to the degradation pathway. • Ligand exchange and removal experiments underline the role of capping agents in catalyst degradation. We apply silver nanoparticles (Ag NPs) as catalysts of CO 2 reduction in a zero-gap gas-flow electrolyser. Ag NPs stabilized by different ligands —branched polyethylenimine (BPEI), polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), and citrate— are used in the experiments. The as-prepared NPs have almost identical initial size distributions, yet their catalytic performance, in terms of achievable current and CO selectivity, is different. During electrolysis all Ag NPs exhibit unambiguous morphology changes; the degradation pathway they follow, however, markedly depends on the chemical nature of the capping agent stabilizing them. Scanning electron micrographs obtained before and after constant-charge electrolyses carried out at different potentials reveal that amongst the studied ligands, BPEI seems to be the most effective stabilizer of Ag NPs; in turn, however, BPEI also limits CO formation the most. In case of PVP, mostly corrosion (particle shrinkage) is observed at practically relevant electrolysing potentials, while the application of PEG leads more to particle coalescence. Ostwald ripening seems to appear only at high applied (H 2 forming) potentials in case of the three afore-mentioned ligands while in case of citrate it becomes significant already at mild (CO forming) voltages. By studying the effects of capping agent removal and exchange we demonstrate that apart from ligands directly attached to the Ag NPs, also the excess of capping agents (adsorbed on the electrode surface) plays a decisive role in determining the extent and mode of catalyst degradation. The results of SEM-based particle sizing are also confirmed by synchrotron based wide-angle X-ray scattering measurements that provide further insight into the evolution of crystallite size and lattice strain in the applied Ag NPs during electrolysis. [ABSTRACT FROM AUTHOR]

Particle-processing industries, such as those for manufacturing pharmaceuticals, ceramics and polymers, require accurate and reliable monitoring and controlling techniques for particle-size distribution to stabilize product quality and maximize productivity. Imaging is a highly valuable monitoring technique because it can measure precise particle-size distributions by detecting particles individually and also can measure particle shape. However, detecting submicron particles or smaller is difficult due to the diffraction of light in the optics. We propose an imaging-based monitoring system that extends the detectable particle-size range towards the submicron level by combining particle-shade and scattered-light imaging. The system consists of newly developed optics and an analysis algorithm. We evaluated the accuracy of the proposed system using polystyrene standard spheres. [Display omitted] • Imaging-based particle sizing system for submicron particles • Particle-shade and scattered-light imaging were combined. • Analytical correction of particle's edge considering diffraction of light • Particle size estimation from intensity of small angle scattered light. • Accuracy of PSD estimation were evaluated using polystyrene spheres. [ABSTRACT FROM AUTHOR]

The ultrasonic spectroscopy method has long been known as a particle size analysis method applicable to concentrated particle suspensions that do not transmit light. On the other hand, it requires prior estimation of density and thermal parameters in addition to the parameters of the surrounding liquid. In this paper, we describe a method for precisely measuring diameter of nano and submicron particles in highly concentrated (∼30 wt%), optically turbid suspensions using dynamic ultrasound scattering (DSS). This method is an acoustic analogue of the dynamic light scattering (DLS) method, which determines the so-called Stokes-Einstein particle size by measuring the diffusion coefficient. Here, the only parameters required in the DSS analysis are the simultaneously measurable sound velocity of the suspension and the viscosity of the solvent (water), which is significantly less a priori information required. In addition, the required sample volume is only 50 µL, which can easily accommodate precious samples. However, as the concentration increases, two effects cannot be ignored: interference from the particle structure (static structure factor) and long-ranged interaction (hydrodynamic interaction). This study focuses on the long-wavelength approximation of ultrasound, which has a longer wavelength than light, and the advantages of simplifying these complex interactions and providing a means to determine particle size by a different route than conventional ultrasonic methods. Finally, the advantages and disadvantages of this method are also discussed. [Display omitted] [ABSTRACT FROM AUTHOR]

Dynamic Light Scattering is a well-established technique used in particle sizing. An alternative procedure for Dynamic Light Scattering time series processing based on spectral entropy computation and Artificial Neural Networks is described. An error analysis of the proposed method was carried out and the results on both the simulated and on the experimental DLS time series are presented in detail. The results reveal the possibility of designing an advanced sensor capable of detecting particles with a size bigger than a threshold using this alternative for processing the DLS time series.

"Surgical smoke" is an airborne by-product of electrosurgery comprised of vapour and suspended particles. Although concerns exist that exposure may be harmful, there is a poor understanding of the smoke in terms of particle size, morphology, composition and biological viability. Notably, it is not known how the biological tissue source and cutting method influence the smoke. The objective of this study was to develop a collection method for airborne by-product from surgical cutting. This would enable comprehensive analyses of the particulate burden, composition and biological viability. The method was applied to compare the electrosurgical smoke generated (in the absence of any evacuation mechanism) with the aerosolized/airborne by-products generated by ultrasonic and high-speed cutting, from bone and liver tissue cutting. We report a wide range of particle sizes (0.93–806.31 μm for bone, 0.05–1040.43 μm for liver) with 50% of the particles being <2.72 μm (~PM2.5) and 90% being <10 μm (PM10). EDX and biochemical analysis reveal components of biological cells and cellular metabolic activity in particulate from liver tissue cut by electrosurgery and ultrasonic cutting. We show for the first time however that bone saws and ultrasonic cutting do not liberate viable cells from bone. [ABSTRACT FROM AUTHOR]

The state of a suspension is crucial with regard to processing pathways, functionality and performance of the end product. In the past decade, substantial progress has been made in designing highly specialized and functionalized particles. In current particle technology, besides classic particle properties such as particle size distribution, shape and density, surface properties play an essential role for processing, product specification and use. For example, in medical therapy, analytical diagnostic applications, as well as in separation processing and harvesting of high-valued materials, magnetic micro- and nanoparticles play an increasing role. In addition to traditional parameters such as size, the particle magnetization has to be quantified here.Sedimentation techniques have been used for hundreds of years to determine the geometrical characteristics of dispersed particles. Numerous national and international standards regarding these techniques have been published. Mainly due to the fast growing market share of laser scattering techniques over the past two decades, most customers these days are not aware of some advantageous features of particle characterization via a first-principle fractionating approach such as sedimentation. This is unfortunate as sedimentation techniques have made huge technological leaps forward regarding electronics, sensors and computing abilities.This paper aims to give a short review about different cumulative and incremental sedimentation approaches to measure the particle size distribution. It focuses mainly on the in-situ visualization (STEP-Technology®) of particle migration in gravitational and centrifugal fields. It describes the basics of the new multi-sample measuring approaches to quantify the separation kinetics by spatial and time-resolved particle concentration over the entire sample height. Based on these data, the sedimentation velocity and particle size distribution are elucidated and estimates of accuracy, precision and experimental uncertainties are discussed. Multi-wavelength approaches, correction of higher concentration, and the influence of rheological behavior of continuous phase will also be discussed. Applications beyond the traditional scope of sedimentation analysis are presented. This concerns the in-situ determination of hydrodynamic particle density and of magnetophoretic velocity distributions for magnetic particulate objects.

In this paper, we consider the two-dimensional Fredholm integral equation of the first kind. The kernel of this equation models the scattering of a laser beam by spheroids having the same fixed orientation. The unknown function under the integral describes the distribution of spheroids along two semi-axes. The input data are the diffraction pattern corresponding to the scattering of the laser beam by the particles. We show that the Tikhonov regularization method allows one to reconstruct two-dimensional distributions in the case when the diffraction pattern is modulated by white noise with relative amplitude up to 1%. In applications, this means novel possibility of obtaining two-dimensional particle size distributions, rather than one-dimensional ones, as in the classical version of the method. This significantly expands the capabilities of particle sizing via static laser diffraction technique. We show that the solution of the corresponding equation is unique in L 2 space and exists when the right-hand-side function is in a set dense in L 2 . We provide test experimental results in the framework of laser ektacytometry of red blood cells, which serves as the main application of the proposed approach presently. [ABSTRACT FROM AUTHOR]

During the past two decades the nanomedicine field has experienced significant progress. To date, over sixty nanoparticle (NP) formulations have been approved in the US and EU while many others are in clinical or preclinical development, indicating a concerted effort to translate promising bench research to commercially viable pharmaceutical products. The use of NPs as novel drug delivery systems, for example, can improve drug safety and efficacy profiles and enable access to intracellular domains of diseased cells, thus paving the way to previously intractable biological targets. However, the measurement of their physicochemical properties presents substantial challenges relative to conventional injectable formulations. In this perspective, we focus exclusively on particle size, a core property and critical quality attribute of nanomedicines. We present an overview of relevant state-of-the-art technologies for particle sizing, highlighting the main parameters that can influence the selection of techniques suitable for a specific size range or material. We consider the increasing need, and associated challenge, to measure size in physiologically relevant media. We detail the importance of standards, key to validate any measurement, and the need for suitable reference materials for processes used to characterize novel and complex NPs. This perspective highlights issues critical to achieve compliance with regulatory guidelines and to support research and manufacturing quality control. [ABSTRACT FROM AUTHOR]

Dynamic Light Scattering is a technique currently used to assess the particle size and size distribution by processing the scattered light intensity. Typically, the particles to be investigated are suspended in a liquid solvent. An analysis of the particular conditions required to perform a light scattering experiment on particles in air is presented in detail, together with a simple experimental setup and the data processing procedure. The results reveal that such an experiment is possible and using the setup and the procedure, both simplified to extreme, enables the design of an advanced sensor for particles and fumes that can output the average size of the particles in air.

Titanium dioxide (TiO 2 ) pigment is a non-toxic, particulate material in widespread use and found in everyone's daily life. The particle size of the anatase or rutile crystals are optimised to produce a pigment that provides the best possible whiteness and opacity. The average particle size is intentionally much larger than the 100 nm boundary of the EU nanomaterial definition, but the TiO 2 pigment manufacturing processes results in a finite nanoscale content fraction. This optically inefficient nanoscale fraction needs to be quantified in line with EU regulations. In this paper, we describe the measurement procedures used for product quality assurance by three TiO 2 manufacturing companies and present number-based primary particle size distributions (PSDs) obtained in a round-robin study performed on five anatase pigments fabricated by means of sulfate processes in different plants and commonly used worldwide in food, feed, pharmaceutical and cosmetic applications. The PSDs measured by the three titanium dioxide manufacturers based on electron micrographs are in excellent agreement with one another but differ significantly from those published elsewhere. Importantly, in some cases, the PSDs result in a different regulatory classification for some of the samples tested. The electron microscopy results published here are supported by results from other complementary methods including surface area measurements. It is the intention of this publication to contribute to an ongoing discussion on size measurements of TiO 2 pigments and other particulate materials and advance the development of widely acceptable, precise, and reproducible measurement protocols for measuring the number-based PSDs of particulate products in the size range of TiO 2 pigments., (Copyright © 2024, Theissmann et al.)

The present work envisages the development of a novel and low-cost self-mixing interferometry (SMI) technology-based single particle sensing system in a microchannel chip for real time single micro-scale particle sizing. We proposed a novel theoretical framework to describe the impulse SMI signal expression in the time domain induced by a flowing particle. Using Hilbert transform, the interferometric fringe number of the impulse SMI signal was retrieved precisely for particle size discrimination. For the ease of particle sensing, a hydrodynamic focusing microfluidic channel was employed by varying the flow rate ratio between the sample stream and the sheath liquid, and the particle stream of a controllable width was formed very easily. The experimental results presented good agreement with the theoretical values, providing a 300 nm resolution for the particle sizing measurement. [ABSTRACT FROM AUTHOR]

Multi-parameter regularization can improve the over-regularization or under-regularization in the regularized inversion of dynamic light scattering (DLS) data. However, the regularization parameter selected by a fixed adjustment factor is not independent of the other parameters, which results in all the selected parameters being affected by the singular value of the truncation point. This leads to oscillations and false peaks in the recovered particle size distribution (PSD) as the noise in the data increases. In this paper, the singular value distribution characteristics are investigated, and this leads to the proposal of a novel multi-parameter selection method. Using the proportional relationship between two adjacent singular values, a regular parameter function is constructed for the parameter selection. Parameter optimization is performed using fixed point iteration to obtain the regularization parameter sequence corresponding to the singular value distribution. Thus, the effects of small singular values on noise are suppressed. Simulated DLS data for monomodal, closely-spaced bimodal, widely-spaced bimodal and trimodal PSDs were inverted under a range of different noise levels. The results show that, the proposed method greatly reduces the oscillations and false peaks and significantly improves the resolution of the peak position in the recovered PSDs as the noise in the data increases. The performance of the method was also verified using experimental DLS data. Unlabelled Image • Regularization parameter chosen by a fixed adjustment factor has noise amplification. • Accurate particle sizing rely on regularization parameter change with singular values. • Optimized regularization parameter can be achieved by two adjacent singular values. [ABSTRACT FROM AUTHOR]

Abstract The potential for inadvertent inhalation of over-the-counter (OTC) aerosol/powder drug products for topical application requires understanding of the characteristic size distributions of the airborne particles or droplets generated when these products are used as per the directions on the product label. Particle/droplet size is an important factor in determining the depth of particle penetration into the respiratory system after inhalation. Because particles penetrating beyond the larynx into the lung may lead to adverse respiratory effects, OTC aerosol or powder drug product particle size distribution is important to characterize. In this study, laser diffraction was used to analyze the particle size distribution of 32 currently marketed OTC drug products as emitted after actuation or air dispersion from their final package. Among the products surveyed were sunscreens, antiperspirants, topical analgesics, skin protectants, and acne products. The results may be useful to the U.S. Food and Drug Administration in its mission to protect as well as promote public health. [ABSTRACT FROM AUTHOR]

To prevent appearance of false peaks and avoid the loss of true peak information in the inversion of multi dispersive particles, in the regularized inversion, regular parameter functions are constructed by truncating the small singular values and using regulation factors. It not only eliminates noise amplification by small singular values, but also avoids over regularization or under regularization caused by improper single regularization parameters. Over regularization can cause the loss of peak information in the inversion results, and the under regularization will lead to false peaks, peak petals or burrs. Therefore, the multi parameter regularization significantly improves the noise-resistibility and multi peak recognition ability of the inversion method. The inversion results of the simulated and measured dynamic light scattering data show that the multi parameter regularization method can effectively eliminate the false peaks, peak petals and burrs, and realize the accurate measurement of the multi peak particle system. [ABSTRACT FROM AUTHOR]

Abstract In a typical oil-in-water emulsion drug product, oil droplets with varied sizes are dispersed in a water phase and stabilized by surfactant molecules. The size and polydispersity of oil droplets are critical quality attributes of the emulsion drug product that can potentially affect drug bioavailability. More critically, to ensure accuracy in characterization of the finished drug product, analytical methods should introduce minimal physical perturbation (e.g., temperature variation or dilution) before the analysis. The classical methods of dynamic light scattering or electron microscopy can be used but they generally require sample dilution or harsh preparation conditions, respectively. By contrast, the size distribution of emulsion formulations can be assessed with a simple and noninvasive solution nuclear magnetic resonance method, namely, two-dimensional Diffusion Ordered SpectroscopY. The two-dimensional Diffusion Ordered SpectroscopY method probed signal decay of methyl resonances from oil and sorbate molecules and was applied to 3 types of U.S.-marketed emulsion drug products, that is, difluprednate, cyclosporine, and propofol, yielding measured droplet sizes of 40-280 nm in diameter. The high precision of ±6 nm of the new nuclear magnetic resonance method allows analytical differentiation of lot-to-lot and brand-to-brand droplet size differences in emulsion drug products, critical for drug-quality development, control, and surveillance. [ABSTRACT FROM AUTHOR]

The state of a suspension is crucial with regard to processing pathways, functionality and performance of the end product. In the past decade, substantial progress has been made in designing highly specialized and functionalized particles. In current particle technology, besides classic particle properties such as particle size distribution, shape and density, surface properties play an essential role for processing, product specification and use. For example, in medical therapy, analytical diagnostic applications, as well as in separation processing and harvesting of high-valued materials, magnetic micro- and nanoparticles play an increasing role. In addition to traditional parameters such as size, the particle magnetization has to be quantified here. Sedimentation techniques have been used for hundreds of years to determine the geometrical characteristics of dispersed particles. Numerous national and international standards regarding these techniques have been published. Mainly due to the fast growing market share of laser scattering techniques over the past two decades, most customers these days are not aware of some advantageous features of particle characterization via a firstprinciple fractionating approach such as sedimentation. This is unfortunate as sedimentation techniques have made huge technological leaps forward regarding electronics, sensors and computing abilities. This paper aims to give a short review about different cumulative and incremental sedimentation approaches to measure the particle size distribution. It focuses mainly on the in-situ visualization (STEP-Technology®) of particle migration in gravitational and centrifugal fields. It describes the basics of the new multi-sample measuring approaches to quantify the separation kinetics by spatial and time-resolved particle concentration over the entire sample height. Based on these data, the sedimentation velocity and particle size distribution are elucidated and estimates of accuracy, precision and experimental uncertainties are discussed. Multi-wavelength approaches, correction of higher concentration, and the influence of rheological behavior of continuous phase will also be discussed. Applications beyond the traditional scope of sedimentation analysis are presented. This concerns the in-situ determination of hydrodynamic particle density and of magnetophoretic velocity distributions for magnetic particulate objects. [ABSTRACT FROM AUTHOR]

This work investigates nanoparticles formation process in light-duty gasoline direct-injection engines operated in homogeneous combustion. The analysis specifically focuses on the contribution of particles in the range of 10–23 nm, which are expected to be taken into account in future emission regulations. Experiments were carried out on a single-cylinder 0.4-L displacement gasoline direct-injection optical engine. Exhaust gases were analyzed by means of a commercial device (DMS500) to obtain a quantitative measurement of the particulates number and size. Optical diagnostics (broadband color imaging and liquid phase laser-induced fluorescence) were employed to correlate the exhaust measurements to the in-cylinder physical phenomena. The main leverages to control soot particulates formation were investigated. The engine temperature was found to have a significant impact during the entire warm-up phase on the global particulates number and also on the relative contribution of the 10–23 nm range to the total particulates number. Injection phasing has also a primary role in the formation of particulates in the small range of the spectrum when operating in mild stratified combustion mode. On the other hand, an increased in-cylinder aerodynamic (e.g. combined swirl-tumble motion) has a positive impact in reducing global particulates number but also causes an increase of the 10–23 nm relative contribution. Optical diagnostics helped establishing a relationship between the detection of liquid film, the consequent pool fires and the exhaust gas measurements. The evaporation of the liquid film detected on the injector nozzle and the intake valve right after the injection appears to be decisive for the formation of nanoparticles in pool-fire mode. The experimental results indicate that when pool fires were detected, the particulates number increased drastically in the whole range of the spectrum including the 10–23 nm range. Authors relate this effect to in-homogeneities in the fuel-mixing field induced by the evaporation of the liquid film. [ABSTRACT FROM AUTHOR]

Bacille Calmette–Guerin, BCG, is a live attenuated bovine tubercle bacillus used for the treatment of non-muscle invasive bladder cancer. In this study, an Electrical Sensing Zone (ESZ) method was developed to measure the particle count and the size of BCG immunotherapeutic (BCG IT), or ImmuCyst® product using a Coulter Counter Multisizer 4® instrument. The focus of this study was to establish a baseline for reconstituted lyophilized BCG IT product using visible and sub-visible particle concentration and size distribution as reportable values. ESZ method was used to assess manufacturing process consistency using 20 production scale lots of BCG IT product. The results demonstrated that ESZ can be used to accumulate product and process knowledge of BCG IT.

High accuracy measurement of size is essential in physical and biomedical sciences. Various sizing techniques have been widely used in sorting colloidal materials, analyzing bioparticles and monitoring the qualities of food and atmosphere. Most imaging-free methods such as light scattering measure the averaged size of particles and have difficulties in determining non-spherical particles. Imaging acquisition using camera is capable of observing individual nanoparticles in real time, but the accuracy is compromised by the image defocusing and instrumental calibration. In this work, a machine learning-based pipeline is developed to facilitate a high accuracy imaging-based particle sizing. The pipeline consists of an image segmentation module for cell identification and a machine learning model for accurate pixel-to-size conversion. The results manifest a significantly improved accuracy, showing great potential for a wide range of applications in environmental sensing, biomedical diagnostical, and material characterization.