Nonporous Core Research Articles

Investigation of Island Growth on Fluidized Particles Coated by Means of Aerosol

In this study, an aerosol fluidized bed is used to coat particles. A new aerosol generator is used to obtain coating solution droplets with a diameter of around 1 μm or smaller. Glass particles, which have a mean diameter of 653 μm, were the non-porous core material and the coating solution was sodium benzoate. Scanning electron microscope pictures were analyzed by MATLAB image processing for evaluating the coverage with the curvature effect. Monte Carlo simulation was used to describe the coating of fluidized particles by aerosol droplets. The purpose of this work was the determination of possible island growth on particles, and investigation of the reasons of it by comparing the experimental and simulation results. The preferential deposition of droplets on already occupied positions is seen as the main possible reason for island growth.

Core shell stationary phase for a novel separation of some COVID-19 used drugs by UPLC-MS/MS Method: Study of grapefruit consumption impact on their pharmacokinetics in rats

A sensitive and selective UPLC-MS/MS method was developed for the synchronized determination of four drugs used in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), namely, azithromycin, apixaban, dexamethasone, and favipiravir in rat plasma. using a Poroshell 120 EC-C18 column (50 mm × 4.6 mm, 2.7 m) with a high-resolution ESI tandem mass spectrometer detection with multiple reaction monitoring. We used an Agilent Poroshell column, which is characterized by a stationary phase based on non-porous core particles. With a remarkable improvement in the number of theoretical plates and low column backpressure. In addition, the developed method was employed in studying the potential food-drug interaction of grapefruit juice (GFJ) with the selected drugs which affects their pharmacokinetics in rats. The LC-MS/MS operated in positive and negative ionization mode using two internal standards: moxifloxacin and chlorthalidone, respectively. Liquid- liquid extraction of the cited drugs from rat plasma was accomplished using diethyl ether: dichloromethane (70:30, v/v). The analytes were separated using methanol: 0.1 % formic acid in water (95: 5, v/v) as a mobile phase in isocratic mode of elution pumped at a flow rate of 0.3 mL/min. A detailed validation of the bio-analytical method was performed in accordance with US-FDA and EMA guidelines.Concerning the in vivo pharmacokinetic study, the statistical significance between the results of the test groups receiving GFJ along with the cited drugs and the control group was assessed demonstrating that GFJ increased the plasma concentration of azithromycin, apixaban, and dexamethasone. Accordingly, this food–drug interaction requires cautious ingestion of GFJ in patients using (SARS-CoV-2) medications as it can produce negative effects in the safety of the drug therapy. A potential drug–drug interaction is also suggested between those medications requiring a suitable dose adjustment.

Theoretical Analysis of Efficiency of Multi-Layer Core-Shell Stationary Phases in the High Performance Liquid Chromatography of Large Biomolecules.

Modern analytical applications of liquid chromatography require columns with higher and higher efficiencies. In this work, the general rate model (GRM) of chromatography is used for the analysis of the efficiency of core-shell phases having two porous layers with different structures and/or surface chemistries. The solution of the GRM in the Laplace domain allows for the calculation of moments of elution curves (retention time and peak width), which are used for the analysis of the efficiency of bi-layer particles with and without a non-porous core. The results demonstrate that bi-layer structures can offer higher separation power than that of the two layers alone if the inner layer has smaller surface coverage (retentivity) and the pore size and pore diffusion of the outer layer is either equal to or higher than that of the inner layer. Even in the case of core-shell phases, there is an increase in resolution by applying the bi-layer structure; however, we can always find a mono-layer core-shell particle structure with a larger core size that provides better resolution. At the optimal core size, the resolution cannot be further improved by applying a bi-layer structure. However, in case of the most widely produced general-purpose core-shell particles, where the core is ∼70% of the particle diameter, a 15–20% gain of resolution can be obtained by using well-designed and optimized bi-layer core-shell phases.

Quantification of free, dissolved combined, particulate, and total amino acid enantiomers using simple sample preparation and more robust chromatographic procedures

The goal of this work was to develop amino acid (AA) quantification protocols using simple sample preparation steps and new chromatographic conditions optimized for a hybrid (organo‐silica) C18 column resistant to alkaline samples in borate buffer. This resistance allows for larger injection volumes, and thus stronger detected signals (~3 times stronger), higher precision, and lower analysis costs compared with previous methods. Enantiomeric and non‐enantiomeric separations of AA were possible in less than 0.5 mL of AA‐poor water samples. Results showed that a high salt content and the sample treatment do not lead to AA loss or separation interference. The accuracy and the precision of AA quantification in a natural sample strongly depend on the blank correction. The limits of detection, measured based on the variability of these blanks, were 0.007–3.6 nM depending on the AA. The protocols developed here allow for the quantification of all forms of AA (i.e., free, dissolved combined, particulate, and total) in most natural waters, including deep ocean waters. It was even possible to quantify many AA in ultrapure water after blank correction. Despite the injection of a relatively high volume (100 µL) of alkaline borate solutions, the hybrid C18 column showed no sign of performance degradation after more than 700 injections. This durability reduces the cost of AA analysis and provides a more consistent separation. The analysis time can be greatly reduced by the use of stationary phases with a nonporous core and extended pH stability as they become available.

3D photonic crystals with a hierarchical pore structure

Perfect 3D film photonic crystals are synthesized from submicron spherical silica particles consisting of a nonporous core and a mesoporous shell. The obtained photonic crystals with a hierarchical pore arrangement—transport macropores between particles and mesopores inside the shell—are promising for application in optical gas sensors.

Pushing the performance limits of reversed-phase ultra high performance liquid chromatography with 1.3 μm core–shell particles

Innovative columns made with very small core–shell particles (1.0–1.4μm) were investigated over a wide experimental space using state-of-the-art ultra high performance liquid chromatography (UHPLC) instruments. Among the columns tested is one that is now commercially available and is made with 1.3μm core–shell particles consisting of non-porous cores about 0.9μm in size and porous shells <0.2μm thick. This work demonstrated that exceptionally low observed minimum plate heights of 2.2μm could be obtained using columns packed with 1.3μm particles, corresponding to a plate count of over 450,000 plates/m. It was shown that only low volume columns allow operation under optimal conditions with current top-of-the-line UHPLC instruments. It was also demonstrated that the loss in performance caused by frictional heating effects remains negligible. Finally, the practical utility of these columns was confirmed with several real-world applications requiring extreme resolving power (i.e. peptide mapping, sample typical of metabolomic studies and crude human insulin). The performance achieved was compared to that of a reference UHPLC column packed with 1.7μm fully porous particles. The column packed with 1.3μm particles gave peak capacity values that were 20–40% higher than the reference column for the same analysis time.

Core shell stationary phases for a novel separation of triglycerides in plant oils by high performance liquid chromatography with electrospray-quadrupole-time of flight mass spectrometer

A new method for the analysis of triglycerides (TAGs) in vegetable oils was developed using a Poroshell 120 EC-C18 column (3.0mm×50mm, 2.7μm) with a high resolution ESI-Q-ToF tandem mass spectrometer as detection system. We used an Agilent Poroshell column, which is characterized by a recently developed stationary phase based on non-porous core particles. The results highlighted the advantages of this column in terms of the dramatic improvement in the number of theoretical plates and in low column backpressure. The developed method enabled us to analyze complex mixtures of more than 40 TAGs within less than 25min and with a low backpressure (lower than 100bar), and represents the first application of a core-shell stationary phase in reverse phase HPLC using an ESI-Q-ToF as detection system. The method was optimized on standards of TAGs, validated and applied to several plant oils. By a quantitative point of view, the method showed a very good linearity (r2>0.999) in the range 0.1–2.4μg/g; high intra- and inter-day precision both in terms of retention times (RSD%<0.04%) and peak areas (RSD%<0.3%). Limits of detection and quantitation were lower than 0.03μg/g and 0.10μg/g, respectively.

A Fast and Effective Method for Packing Nano-LC Columns with Solid-Core Nano Particles Based on the Synergic Effect of Temperature, Slurry Composition, Sonication and Pressure

Nano-LC columns of different lengths (14–35 cm), 75 μm i.d., were packed with solid-core C18 particles using a conventional HPLC system at low pressure (375 bar) and without expensive tools and fittings. Solid-core particles consist of a solid, non-porous core surrounded with a shell of a porous layer with a very narrow particle size distribution. This geometry allows a faster diffusion of the analytes compared to porous particles, reducing the C term of the Knox plot. Different slurries of packing material were evaluated and tested. The packing procedure was carried out at room temperature and at 70 °C to evaluate the influence of this parameter on the overall process. The synergic action of pressure, temperature and sonication contributed to columns of various lengths in the packing process. The columns were tested at room temperature taking into account the following parameters: Knox plots, specific permeability and peak capacity. Reduced heights of theoretical plates, h, ranged between 3.8 and 5.1 at ν between 2 and 6. An LC-MS test was carried out with a Direct-EI LC-MS instrument.

Glutathione-sensitive nanoplatform for monitored intracellular delivery and controlled release of Camptothecin

We report the design, synthesis, characterization and in vitro testing of a novel nanodrug based on a covalent linking model that allows intracellular controlled release of the pharmaceutical payload. A new synthetic strategy is implemented by direct coupling of as-synthesized (pyridin-2-yldisulfanyl)alkyl carbonate derivatives of camptothecin (CPT) with thiol groups of silica hybrid nanoparticles containing a non-porous core and a mesoporous shell. Upon reaction with thiols in physiological conditions, disulfide bridge cleavage occurs, releasing the naked drug after an intramolecular cyclization mechanism. Additional incorporation of a fluorophore into particles core facilitates imaging at the subcellular level for the monitoring of uptake and delivery. Confocal microscopy experiments in HeLa cervix cancer cells confirms that nanoparticles enter the cells by endocytosis but are able to escape from endo-lysosomes and enter the cytosolic compartment to release their cargo. The incorporation to cells of L-buthionine-sulfoximine, a glutathione inhibitor allows concluding that the intracellular releasing mechanism is mainly driven by the reducing activity of this tripeptide. This camptothecin nanoplatform shows the same cytotoxic activity than the free drug and is clearly superior to those release systems depending on enzymatic hydrolysis (as determined by calculation of the IC50 ratios).

Enhanced luminescence of photosensitizer-based mesoporous silica nanocomposites via energy transfer from conjugated polymer

A unique assembly approach was developed to fabricate conjugated polymer and photosensitizer-doped mesoporous silica nanoparticles with effective Förster resonance energy transfer (FRET) from poly[(9,9-di(3,30-N,N0-trimethylammonium)-propylfluorenyl-2,7-diyl)-alt-co-(1,4-phenylene)] (PFP) to porphyrin-based photosensitizers (PSs). PFP and silica nanoparticles form a complex through electrostatic interactions, and efficient energy transfer from PFP to porphyrin-based PSs occurs upon irradiation. This approach is stable, effective, and diversified. PS-doped mesoporous silica nanoparticles showed three- to four-fold enhanced emission with the excitation of the maximum absorption wavelength of PS in the presence of PFP in comparison to the case without PFP. Doping fluorescence dyes into the nonporous core and adjusting the content of PS conjugated with the shell can endow the silica nanoparticles with a combinational optical signal of dyes and PS. These silica nanoparticles exhibit further improved performance on the basis of enhanced energy transfer offered by light-harvesting conjugated polymers.

Repeatability of the efficiency of columns packed with sub-3 μm core–shell particles: Part I. 2.6 μm Kinetex-C18 particles in 4.6 mm and 2.1 mm × 100 mm column formats

The column-to-column repeatability of the mass transfer mechanism in columns packed with sub-3μm shell particles was investigated. The parameters of this mechanism were measured for twelve columns (six 2.1mm×100mm and six 4.6mm×100mm) packed with the same batch of 2.6μm Kinetex-C18 particles (Phenomenex, CA, USA). For both series, the manufacturer provided columns at different positions in the efficiency distribution given by the quality test control. Three compounds were used, uracil, naphthalene and insulin. The reduced longitudinal diffusion term was measured with the peak parking (PP) method, the reduced solid–liquid mass transfer resistance term was given by a combination of the PP results and a model of effective diffusion in ternary composite materials (non-porous cores, concentric porous shell, and eluent matrix), validated previously. The overall eddy diffusion term was obtained by subtraction of these two HETP terms from the overall reduced HETP measured by numerical integration of the entire peak profiles. The results demonstrate that the dispersion of the column efficiencies is only due to the random nature of the packing process. At the highest reduced velocity achieved, the relative standard deviations (RSDs) of the eddy diffusion term for the 2.1mm I.D. columns were ca. 7% and 3% for the low molecular weight compounds and for insulin, respectively. For the 4.6mm I.D. columns, these RSDs were 15% and 5%, respectively. The larger RSDs for the 4.6mm I.D. columns is explained by the exceptionally low value of the eddy diffusion term.

Validation of BET specific surface area for heterogeneous Ziegler-Natta catalysts based on αS-plot

Specific surface area based on the BET method in N2 adsorption has historically posed poor correlation with olefin polymerization activity of heterogeneous Ziegler-Natta (ZN) catalysts. We have investigated the validity of the BET surface area for ZN catalysts based on the αS-plot method, where non-porous core–shell MgO/MgCl2/TiCl4 catalysts were used as a reference material. The αS-plots for typical industrial ZN catalysts clarified the presence of two classes of micropores and resultant difficulty to isolate a multilayer adsorption region for the BET method. The results cast doubt on the application of the BET method to evaluate the surface area of heterogeneous ZN catalysts.

Repeatability of the efficiency of columns packed with sub-3 μm core–shell particles: Part II. 2.7 μm Halo-ES-Peptide-C18 particles in 4.6 mm and 2.1 mm × 100 mm column formats

The column-to-column repeatability of the mass transfer kinetics in columns packed with sub-3μm shell particles was investigated. The parameters of this kinetics were measured for twelve columns (six 2.1mm×100mm and six 4.6mm×100mm) packed with the same batch of 2.7μm Halo-ES-Peptide-C18 particles (Advanced Material Technologies, Wilmington, DE, USA). For both series, the manufacturer provided columns at different positions in the efficiency distribution given by the quality test control. Three compounds were used, uracil, naphthalene and insulin. The reduced longitudinal diffusion term was measured with the peak parking (PP) method; the reduced solid–liquid mass transfer resistance term was given by a combination of the PP results and the most accurate model of effective diffusion in ternary composite materials (non-porous cores, concentric porous shell, and eluent matrix), validated previously. The overall eddy diffusion term was obtained by subtraction of these two HETP terms from the overall reduced HETP measured by numerical integration of the entire peak profiles. The results demonstrate that the dispersion of the column efficiencies is mostly due to the random nature of the packing process and the associated eddy diffusion term. At the highest reduced velocity achieved, the relative standard deviations (RSDs) of the eddy diffusion term for the 2.1mm I.D. columns were ca. 5 and 10% (with average values A(ν)=2.3 and 8.5) for naphthalene and uracil, respectively. For the 4.6mm I.D. columns, these RSDs were 3 and 5%, respectively, with average values A(ν)=1.5 and 2.7.

Nano-liquid chromatography coupled with mass spectrometry: Separation of sulfonamides employing non-porous core–shell particles

In this paper, nano-liquid chromatography coupled with mass spectrometry was used for the simultaneous determination of 18 sulfonamides. Preliminary experiments were carried out to investigate selectivity of three different stationary phases. Best results were achieved utilizing a capillary column (100μm I.D.) packed in our laboratory following the slurry packing procedure with a recent commercialized stationary phase, Kinetex® C18 core–shell. A binary mobile phase, consisting of water and acetonitrile and both containing 0.1% (v/v) formic acid, was employed in a gradient mode at a low flow rate (190nL/min). Applying these conditions, baseline separation of studied compounds was obtained in about 35min. Although sulfathiazole and sulfapyridine were resolved from the other drugs, they were not separated from each other. Sensitivity was improved by on-column focusing evaluating the appropriate sample solvent and establishing the maximum injection volume. Comparison between UV and mass spectrometric detection was done. Milk samples spiked with sulfonamides were subjected to a rapid pre-treatment by means of acidic deproteinization followed by solid-phase extraction, and analyzed with the developed method. The detection limits obtained in milk were in the range of 8–96μg/kg, however they were low enough according to the regulations set-up by the European Commission. Calibration curves showed good linearity (R2>0.995) in the studied concentration ranges.

Kinetic investigation of narrow-bore columns packed with prototype sub-2 μm superficially porous particles with various shell thickness

The recent successful breakthrough of sub-3 μm shell particles in HPLC has triggered considerable research efforts toward the design of new brands of core-shell particles. We investigated the mass transfer mechanism of a few analytes in narrow-bore columns packed with prototype 1.7 μm shell particles, made of 1.0, 1.2, and 1.4 μm solid nonporous cores surrounded by porous shells 350, 250, and 150 nm thick, respectively. Three probe solutes, uracil, naphthalene, and insulin, were chosen to assess the kinetic performance of these columns. Inverse size exclusion chromatography, peak parking experiments, and the numerical integration of the experimental peak profiles were carried out in order to measure the external, internal, and total column porosities, the true bulk diffusion coefficients of these analytes, the height equivalent to a theoretical plate, the longitudinal diffusion term, and the trans-particle mass transfer resistance term. The residual eddy diffusion term was measured by difference. The results show the existence of important trans-column velocity biases (7%) possibly due to the presence of particle multiplets in the slurry mixture used during the packing process. Our results illustrates some of the difficulties encountered by scientists preparing and packing shell particles into narrow-bore columns.

Engineering and optimization of nano- and mesoporous silica fibers using sol–gel and electrospinning techniques for sorption of heavy metal ions

In this paper, we report on a novel design strategy of an efficient sorbent for removal of trace contaminants from water. This kind of sorbent is composed of a nonporous core of SiO 2 nanofiber and a mesoporous shell (denoted as nSiO 2@mSiO 2 (“n” means “nonporous” and “m” means “mesoporous”)). The nSiO 2@mSiO 2 fiber possesses a continuously long fibrous shape and mesoporous micromorphology, thus, showing both high sorption capacity and separability. The flexible nonporous SiO 2 nanofiber was prepared with electrospinning first, followed by covering a mesoporous SiO 2 shell based on a modified Stöber method using CTAB (cetyltrimethylammonium bromide) as the directing agent for formation of the mesopores. Also, functional thiol groups were grafted on the nSiO 2@mSiO 2 to enhance its performance. With a large specific surface area and long fibrous morphology, the nSiO 2@mSiO 2 fiber and its thiol-functionalized counterpart exhibit impressive performance on removal of Pb 2+ and Cd 2+ from water. Furthermore, the flexible texture and fibrous morphology of the nSiO 2@mSiO 2 fiber also made the removal of metal ions and the separation process more convenient and efficient, implying that the nSiO 2@mSiO 2 fiber could have great potential for industrial applications.

Some practical comparisons of the efficiency and overloading behaviour of sub-2 μm porous and sub-3 μm shell particles in reversed-phase liquid chromatography

At their optimum flow, sub-3 μm superficially porous or “shell” particles demonstrate similar efficiency to sub-2 μm totally porous particles. The performance of 0.21 cm i.d shell columns is however inferior to those of 0.46 cm i.d., presumably due to packing difficulties. At high flow, shell columns can give flatter Knox curves due to lower operating pressure (half or less of that of the totally porous particles) producing less frictional heating, which combined with the increased thermal conductivity of their non-porous core, gives more efficient heat dissipation. However, the effects of frictional heating for sub-2 μm columns are considerably exaggerated when using pure ACN as mobile phase, as it has a thermal conductivity 3 times less than that of pure water, leading to poorer heat dissipation. Overloading is already problematic for ionised solutes, a group which contains many pharmaceuticals and compounds of clinical relevance, on conventional columns (5 μm porous particles). However, it becomes a more serious issue for both new column types, partially as a result of their very high efficiency, which concentrates the sample as a very narrow band. The sample capacity of one type of shell particle was estimated to be 60% of that of the small totally porous particles, in line with the fraction of the particle volume that is porous. Due to overloading, it is barely possible to achieve perfect peak symmetry for ionised acids or bases with either of these new column types, even by injecting the lowest amounts of sample detectable by UV. While ammonium formate and potassium phosphate buffers gave similar results in overloading studies, use of formic acid as sole mobile phase additive is not recommended for these solutes, as its ionic strength is too low, leading to a catastrophic deterioration in efficiency when sample concentrations of even a few mg/L are injected.

Solvent Effects on Morphologies of Mesoporous Silica Spheres Prepared by Pseudomorphic Transformations

In surfactant-induced, pseudomorphic transformations of submicrometer-sized nonporous spheres to mesoporous silica spheres, the surface morphologies of the products depend on the solvent used during the initial Stöber synthesis. After hydrothermal transformations employing cetyltrimethylammonium bromide (CTAB) as a surfactant, pseudomorphic products of parent silica spheres synthesized in ethanol (HT-SiO2-EtOH) are mesoporous throughout and have smooth surfaces. In contrast, products from spheres synthesized in isopropanol (HT-SiO2-iPrOH) or butanol (HT-SiO2-BuOH) possess highly corrugated shells surrounding a nonporous core. On the basis of 29Si solid-state magic angle spinning (MAS) NMR spectra, this significant change in surface morphology after the hydrothermal transformation is related to small differences in the degree of condensation of the parent silica spheres. In the case of HT-SiO2-EtOH, the higher degree of condensation of the parent spheres limits sphere dissolution, and the transformation is mostly pseudomorphic. For the other two systems, parent spheres are more reactive and release more silica into solution. Porous shells are therefore formed on the surface of the remaining spheres. Morphological changes were investigated by scanning and transmission electron microscopy. The porosity of the mesoporous silica spheres produced by these reactions was determined by nitrogen sorption measurements and small-angle X-ray scattering. The diffusion depth of CTAB was revealed by nanocasting carbon into the mesoporous silica spheres via phenol-paraformaldehyde gas-phase polymerization and subsequently removing the silica structure. As a result of limited surfactant penetration into the cores of HT-SiO2-iPrOH spheres, replicated mesoporous carbon spheres possess a corrugated mesoporous shell and a hollow core.

Comparative study of new shell-type, sub-2 μm fully porous and monolith stationary phases, focusing on mass-transfer resistance

Today sub-2 μm packed columns are very popular to conduct fast chromatographic separations. The mass-transfer resistance depends on the particle size but some practical limits exist not to reach the theoretically expected plate height and mass-transfer resistance. Another approach applies particles with shortened diffusion path to enhance the efficiency of separations. In this study a systematical evaluation of the possibilities of the separations obtained with 5 cm long narrow bore columns packed with new 2.6 μm shell particles (1.9 μm nonporous core surrounded by a 0.35 μm porous shell, Kinetex™, Core-Shell), packed with other shell-type particles (Ascentis Express™, Fused-Core), totally porous sub-2 μm particles and a 5 cm long narrow bore monolith column is presented. The different commercially available columns were compared by using van Deemter, Knox and kinetic plots. Theoretical Poppe plots were constructed for each column to compare their kinetic performance. Data are presented on polar neutral real-life analytes. Comparison of a low molecular weight compounds (MW = 270–430) and a high molecular weight one (MW ∼ 900) was conducted. This study proves that the Kinetex column packed with 2.6 μm shell particles is worthy of rivaling to sub-2 μm columns and other commercially available shell-type packings (Ascentis Express or Halo), both for small and large molecule separation. The Kinetex column offers a very flat C term. Utilizing this feature, high flow rates can be applied to accomplish very fast separations without significant loss in efficiency.

Mesoporous “core–shell” adsorbents and catalysts with controllable morphology

A simple geometrical model is applied to predict the thickness of mesoporous shells over monodisperse spherical particles. As an example, mesoporous Ti-silicate nearly monodisperse particles with the “core–shell” structure, synthesized via the one-pot procedure are considered. The unique features of the materials are orientation of mesopores perpendicularly to the surface of non-porous cores and uniformity of mesoporous shells structure and thickness. This allows considering these materials as interesting catalysts for partial oxidation of bulk organic molecules with hydrogen peroxide.