Monolithic Silica Research Articles

Preparation of monolithic silica HPLC columns with truss-structured skeletons and embedded surfactant-templated mesopores

AbstractMonolithic macro/mesoporous silica gels have been prepared via a sol-gel process using triblock copolymer Pluronic P123 (EO20PO70EO20) as a structure-directing agent. In this synthesis, P123 not only induces phase separation to form macroporous structure but also acts as a supramolecular template to form mesopores with precisely controlled shape and size. Obtained was a monolithic silica composed of continuous truss-like columnar skeletons in which cylindrical mesopores are arranged in a 2D-hexagonal symmetry. These monolithic silica gels have extremely high porosity approaching 90% and exhibited high specific surface area and sharp pore size distribution as revealed by N2 sorption measurements. Combinations of the initial composition and the post-gelation treatment on wet gels allowed the control of physical properties of meso- and macropore structures. The monolithic HPLC columns prepared using these silica gels surface-modified by ODS (octadecylsilyl) ligands gave as many as 140,000 theoretical plates/m for the separation of alkylbenzenes in a reversed-phase mode. Very weak dependence of height equivalent to theoretical plate, H, on the mobile phase velocity was also recognized in comparison with conventional particle-packed columns. Graphical Abstract

Bifunctionalised acid-base hierarchically structured monolithic microreactor for continuous-flow tandem catalytic process of cyanocinnamate synthesis

The results on zirconia-amine bifunctional modification of hierarchically porous silica monoliths for continuous-flow processes ar presented. The study reports the synthesis and properties of the modified porous monoliths and their performance in the tandem process of deacetalization-Knoevenagel condensation reaction. The properties of the materials were studied by thermal analysis, FTIR spectroscopy, XRF and nitrogen adsorption. It was found that both active centres were uniformly distributed along the monolithic cores, and the antagonistic interaction of the acid and base centres was not observed. It was shown that hydrophobicity of the monolith surface has opposite effects on the efficiency of the studied reactions. The overall rate of the tandem process depends on the rate of the condensation reaction. The performance of the bifunctional microreactors was checked and compared with those of cascade-connected monofunctional microreactors and batch reactor. The yield of cyanocinnamate product obtained in both flow systems was ca. 78%; however, pressure drop in the bimodified reactor was only half of that in the cascade. An effective way of water supply to the reaction system has been proposed. The research demonstrates the benefits of using flow-through structured micro-/mesoreactors in tandem reaction processes.

Correction to: Plastic deformation and heat-enabled structural recovery of monolithic silica aerogels

Correction to: Plastic deformation and heat-enabled structural recovery of monolithic silica aerogels

Vacuum-Assisted MonoTrapTM Extraction for Volatile Organic Compounds (VOCs) Profiling from Hot Mix Asphalt.

MonoTrapTM was introduced in 2009 as a novel miniaturized configuration for sorptive sampling. The method for the characterization of volatile organic compound (VOC) emission profiles from hot mix asphalt (HMA) consisted of a two-step procedure: the analytes, initially adsorbed into the coating in no vacuum- or vacuum-assistance mode, were then analyzed following an automated thermal desorption (TD) step. We took advantage of the theoretical formulation to reach some conclusions on the relationship between the physical characteristics of the monolithic material and uptake rates. A total of 35 odor-active volatile compounds, determined by gas chromatography-mass spectrometry/olfactometry analysis, contributed as key odor compounds for HMA, consisting mainly of aldehydes, alcohols, and ketones. Chemometric analysis revealed that MonoTrapTM RGC18-TD was the better coating in terms of peak area and equilibrium time. A comparison of performance showed that Vac/no-Vac ratios increased, about an order of magnitude, as the boiling point of target analytes increased. The innovative hybrid adsorbent of silica and graphite carbon monolith technology, having a large surface area bonded with octadecylsilane, showed effective adsorption capability, especially to polar compounds.

Multiscale simulation of liquid chromatography: Effective diffusion in macro–mesoporous beds and the B-term of the plate height equation

We performed multiscale simulations of analyte sorption and diffusion in hierarchical porosity models of monolithic silica columns for reversed-phase liquid chromatography to investigate how the mean mesopore size of the chromatographic bed and the analyte-specific interaction with the chromatographic interface influence the analyte diffusivity at various length scales. The reproduced experimental conditions comprised the retention of six analyte compounds of low to moderate solute polarity on a silica-based, endcapped, C18 stationary phase with water‒acetonitrile and water–methanol mobile phases whose elution strength was varied via the volumetric solvent ratio. Detailed information about the analyte-specific interfacial dynamics received from molecular dynamics simulations was incorporated through appropriate linker schemes into Brownian dynamics diffusion simulations in three hierarchical porosity models received from physical reconstructions of silica monoliths with a mean macropore size of 1.23 µm and mean mesopore sizes of 12.3, 21.3, or 25.7 nm. The mean mesopore size was found to have a similar influence on the effective mesopore diffusivity as the analyte polarity and the mobile-phase elution strength, which together determine the analyte residence time on a column. A smaller mesopore size attenuated the increase of the effective mesopore diffusivity with increasing mobile-phase elution strength significantly. The effective bed diffusivity was limited by the analyte residence time rather than by morphological details of the mesopore space. The stronger an analyte was retained by the chromatographic interface inside the mesopores, the slower became the mass transfer between the pore space hierarchies and the lower was the effective bed diffusivity. The B-terms of the plate height equation were finally generated with the bed diffusivities and phase-based retention factors derived from the hierarchical porosity models using additional information about the stationary-phase limit obtained from the analysis of analyte–bonded phase contacts. The B-terms highlight analyte- and mobile phase-specific behavior relevant to isocratic and gradient elution conditions in chromatographic practice. In particular, U-shaped B-term curves are observed due to the dominating contribution of the retention factor and the bed diffusivity to the B-term at low and high elution strength of the mobile phase, respectively.

Time-of-Flight Secondary Ion Mass Spectrometry Revealing the Organocatalyst Distribution in Functionalized Silica Monoliths.

Hierarchically porous monolithic silica shows promise as a carrier material for immobilized organocatalysts. Conventional analysis usually includes physisorption, infrared spectroscopy and elemental analysis, among others, to elucidate the pore space and degree of functionalization of the material. However, these methods do not yield information about the spatial distribution of the organic species inside the monolithic reactor. In this work, time-of-flight secondary ion mass spectrometry has been applied to characterize the surface of organically functionalized silica monoliths. Cross sections of a silica monolith functionalized with 4-dimethylaminopyridine were analyzed and the results were compared with physisorption and elemental analysis experiments of the same material. This way, insight into the radial distribution of the catalyst could be achieved, which might assist in interpreting the performance of such reactors in heterogeneous flow catalysis.

Quantitation of Host Cell Proteins by Capillary LC/IMS/MS/MS in Combination with Rapid Digestion on Immobilized Trypsin Column Under Native Conditions.

Host cell protein (HCP) impurities are considered a critical quality attribute of biopharmaceuticals because of their potential to compromise safety and efficacy, and LC/MS-based analytical methods have been developed to identify and quantify individual proteins instead of employing enzyme-linked immunosorbent assay to assess total HCP levels. Native digestion enables highly sensitive detection of HCPs but requires overnight incubation to generate peptides, limiting the throughput of sample preparation. In this study, we developed an approach employing native digestion on a trypsin-immobilized column to improve the sensitivity and throughput. We examined suitable databases for the identification of HCPs derived from Chinese hamster ovary (CHO) cells and selected RefSeq's Chinese Hamster as the optimal database. Then, we investigated methods to identify HCPs with greater efficiency than that of denatured in-solution digestion. Native in-column digestion not only reduced the digestion time from overnight to 10 min but also increased the number of quantified HCPs from 154 to 226. In addition to this rapid digestion methodology, we developed high-throughput LC/MS/MS with a monolithic silica column and parallel reaction monitoring-parallel accumulation-serial fragmentation. The optimized system was validated with synthetic peptides derived from high-risk HCPs, confirming excellent linearity, precision, accuracy, and low limit of detection (LOD) and limit of quantification (LOQ) (1-3 ppm). The optimized digestion and analysis method enabled high-throughput quantification of HCPs, and is expected to be useful for quality control and characterization of HCPs in antibody drugs.

Preparation of DNA nanoflower-modified capillary silica monoliths for chiral separation.

Innovative chiral capillary silica monoliths (CSMs) were developed based on DNA nanoflowers (DNFs). Baseline separation of enantiomers such as atenolol, tyrosine, histidine, and nefopam was achieved by using DNF-modified CSMs, and the obtained resolution value was higher than 1.78. To further explore the effect of DNFs on enantioseparation, different types of chiral columns including DNA strand containing the complementary sequence of the template (DCT)-modified CSMs, DNF2-modified CSMs, and DNF3-modified CSMs were prepared as well. It was observed that DNF-modified CSMs displayed better chiral separation ability compared with DCT-based columns. The intra-day and inter-day repeatability of model analytes' retention time and resolution kept desirable relative standard deviation values of less than 8.28%. DNF2/DNF3-modified CSMs were able to achieve baseline separation of atenolol, propranolol, 2'-deoxyadenosine, and nefopam enantiomers. Molecular docking simulations were performed to investigate enantioselectivity mechanisms of DNA sequences for enantiomers. To indicate the successful construction of DNFs and DNF-modified CSMs, various charaterization approaches including scanning electron microscopy, agarose gel electrophoresis, dynamic light scattering analysis, electroosmotic flow, and Fourier-transform infrared spectroscopy were utilized. Moreover, the enantioseparation performance of DNF-modified CSMs was characterized in terms of sample volume, applied voltage, and buffer concentration. This work paves the way to applying DNF-based capillary electrochromatography microsystems for chiral separation.

Plastic deformation and heat-enabled structural recovery of monolithic silica aerogels

Drying shrinkage during ambient pressure drying of silica gels is made reversible by preventing condensation reactions of surface silanol groups via surface modification. This partial recovery of the gel volume and structure is referred to as the spring-back effect (SBE) and enables the production of monolithic silica aerogels by evaporative drying. The SBE is sometimes completed by annealing at mild temperatures. Similarities between drying-related deformations and deformations induced by mechanical stimuli suggest analogous underlying mechanisms. While the causes of drying shrinkage are relatively well-known, it remains unclear how the relaxation of the structure by drying and annealing occurs across the different length scales. Here we show a complete structural recovery of silica aerogels at the macro- and nano-scale enabled by annealing. We propose that residual deformations after drying and mechanical compression are caused by the entanglement of silica clusters that can be unraveled by annealing at 230 °C. The deformation under loading is interpreted as two different re-arrangement mechanisms for dry and annealed gels, by the sliding of the silica clusters along the loading direction and by the compression of large pores beyond the fractal structure, respectively. Our results demonstrate how the shape and structure of silica aerogels can be restored and controlled by thermal activation, broadening the various applications of these materials. We also emphasize how tuning silica gels to promote a two-step SBE by annealing can pave the way toward the production of larger monolithic aerogels by APD.Graphical

Halogen-Free Purification of Low-Solubility Compounds in Supersaturated Liquid Chromatography Using Monolithic Silica

Halogen-Free Purification of Low-Solubility Compounds in Supersaturated Liquid Chromatography Using Monolithic Silica

Solvent Cavitation during Ambient Pressure Drying of Silica Aerogels.

Ambient-pressure drying of silica gels stands out as an economical and accessible process for producing monolithic silica aerogels. Gels experience significant deformations during drying due to the capillary pressure generated at the liquid-vapor interface in submicron pores. Proper control of the gel properties and the drying rate is essential to enable reversible drying shrinkage without mechanical failure. Recent in operando microcomputed X-ray tomography (μCT) imaging revealed the kinetics of the phase composition during drying and spring-back. However, to fully explain the underlying mechanisms, spatial resolution is required. Here we show evidence of evaporation by hexane cavitation during the ambient-pressure drying of silylated silica gels by spatially resolved quantitative analysis of μCT data supported by wide-angle X-ray scattering measurements. Cavitation consists of the rupture of the pore liquid put under tension by capillary pressure, creating vapor bubbles within the gels. We found the presence of a homogeneously distributed vapor-air phase in the gels well ahead of the maximum shrinkage. The onset of this vapor/air phase corresponded to a pore volume shrinkage of ca. 50 vol % that was attributed to a critical stiffening of the silica skeleton enabling cavitation. Our results provide new aspects of the relation between the shape changes of silica gels during drying and the evaporation mechanisms. We conclude that stress release by cavitation may be at the origin of the resistance of the silica skeleton to drying stresses. This opens the path toward producing larger monolithic silica aerogels by fine-tuning the drying conditions to exploit cavitation.

A Robust Chromatographic Method for Drug Release profiling of liposomal doxorubicin HCl

Liposomes are excellent drug delivery vehicles for chemotherapeutics as they may change the pharmacokinetics of therapeutic compounds, resulting in altered tissues distribution, and in some cases, reduced cytotoxicity and enhanced distribution and efficacy of the active pharmaceutical ingredient (API) at target tissues. Drug release profiles of liposomal formulations are crucial to support equivalence evaluation and quality control in pre- and post-approval stages. We developed an automated chromatographic method for quantifying the drug release profile of liposomal formulations containing doxorubicin to overcome the shortcomings of currently available methods. The newly developed method employs nanoparticle exclusion chromatography (nPEC), using a monolithic silica column coated with polyvinylpyrrolidone to separate the released drug from liposomal encapsulated drug. We evaluated the effects of pH, temperature, and ammonium formate concentration on the drug release rate. The optimized release buffer consisting of 5 % sucrose, 20 mM l-histidine, and 200 mM ammonium formate was selected for the drug release profiling of five liposomal formulations at 47 °C. The drug release profiles of five liposomal doxorubicin formulations were similar. Our automated method requires very small amounts of the sample and provides release profiles with high sensitivity and accuracy. In addition, this method can be applied to other liposomal products to allow for simple, fast, and accurate analysis of in vitro drug release profiling.

Cosolvent-free sol–gel synthesis of macroporous silica gels from tetramethoxysilane–tetraethoxysilane mixtures

Abstract Tetramethoxysilane (TMOS), tetraethoxysilane (TEOS), and their mixtures were used for the cosolvent-free synthesis of macroporous silica gels as precursors for monolithic silica glasses. The liquid-state 29Si nuclear magnetic resonance (NMR) spectroscopy of precursor solutions indicated that cross-transesterification between TMOS and TEOS was completed in a few hours at 20 °C in the presence of an acid catalyst, whereas it was negligible when the catalyst was absent. In the precursor solutions prepared from TMOS, phase separation occurred after gelation, resulting in translucent gels. In contrast, in the solutions prepared from TEOS or a mixture of TMOS and TEOS at a TMOS mole fraction of 0.8, the phase separation can be induced before gelation, and opaque xerogels were easily obtained without fracture. The average size of macroscopic particles and macroporous structures were uniform over opaque xerogels prepared from TEOS. In contrast, in opaque xerogels prepared from the TMOS-rich mixture of TMOS and TEOS, the average particle size and macroscopic porosity inside them were notably smaller than those of the subsurface, probably because of a large exotherm upon gelation and the resulting temperature gradient in the gelling solutions. Such spatial morphology distribution made the sintering of the opaque gels into clear silica glasses difficult. Opaque gels prepared from TEOS and translucent gels prepared from solutions containing TMOS were transformed to clear silica glasses in high yields of ~99% by sintering in a helium atmosphere at 1050–1350 °C. Graphical abstract

Halloysite nanotubes-based hybrid silica monolithic spin tip for hydrophilic solid-phase extraction of sulbactam, cefoperazone, and cefuroxime in whole blood

In this study, we proposed a novel method utilizing polyethyleneimine (PEI)-modified halloysite nanotubes (HNTs)-based hybrid silica monolithic spin tip to analyze hydrophilic β-lactam antibiotics and β-lactamases inhibitors in whole blood samples for the first time. HNTs were incorporated directly into the hybrid silica monolith via a sol-gel method, which improved the hydrophilicity of the matrix. The as-prepared monolith was further modified with PEI by glutaraldehyde coupling reaction. It was found that the PEI-modified HNTs-based hybrid silica monolith enabled a large adsorption capacity of cefoperazone at 35.7 mg g−1. The monolithic spin tip-based purification method greatly reduced the matrix effect of whole blood samples and had a detection limit as low as 0.1 − 0.2 ng mL−1. In addition, the spiked recoveries of sulbactam, cefuroxime, and cefoperazone in blank whole blood were in the range of 89.3–105.4 % for intra-day and 90.6–103.5 % for inter-day, with low relative standard deviations of 1.3–7.2 % and 4.9–10.5 %, respectively. This study introduces a new strategy for preparing nanoparticles incorporated in a hybrid silica monolith with a high adsorption capacity. Moreover, it offers a valuable tool to monitor sulbactam, cefoperazone, and cefuroxime in whole blood from pregnant women with the final aim of guiding their administration.

Significant Waste Reduction in Liquid Chromatography by a Reusable Large-Volume Monolithic Silica Column

Significant Waste Reduction in Liquid Chromatography by a Reusable Large-Volume Monolithic Silica Column

Facile and Rapid Synthesis of Gold Nanoparticles on Unconventional Imine‐ Decorated Silica

AbstractWe demonstrate the reduction of gold (Au) on silica monoliths by surface decoration of amine and imine (formed by reaction of amine present in 3‐amino propyl triethoxy silane (APTES) and acetone) functionalities on the surface of silica. The reduction of Au3+ to Au0 was confirmed by X‐ray diffraction (XRD), UV‐Diffuse reflectance and X‐ray Photo electron spectroscopic techniques. Without employing the conventional strategies with reducing agents like sodium borohydride and sodium citrate, here, the surface functionalized amine and imine was found to reduce the metal ions, additionally, the surface silanols was found to anchor and serve as the adsorption sites to hold the metal ions prior to reduction. The control experiment was performed with silica monoliths without the surface functionalities displayed no evident reduction of Au3+ to their respective metallic form. Interestingly, the reduction of Au was found to be more facile on imine modified silica, due to the strong electrostatic interaction of highly polarized imine with Au3+ ions.

Bicontinuous silica-epoxy nanocomposites by aerogel infusion

Interpenetrated, bicontinuous nanocomposites are formed by fully infusing monolithic mesoporous silica (silica aerogel) with epoxy resin. The long-range connectivity of the silica network facilitates direct load transfer and enforces sample homogeneity. The silica networks are prepared using sol–gel chemistry, informed by new phase diagrams, adapted to maximise reinforcement content in the subsequent bicontinuous composite. The infusibility of the aerogels is correlated to pore characteristics determined by gas sorption, as a function of silica aerogel density. Silica reinforcement loadings of up to 22silica vol.% are fully consolidated, with only a modest reduction in glass transition temperature and no change in cure conditions. The reinforcement improves both hardness (+23 %) and reduced modulus (+17 %) of the baseline resin. These properties increase with aerogel content viaa power law relationship which demonstrates the direct role of the connected silica phase as a reinforcing network and motivates future studies to extend the applicable range.

On the modelling of the effective longitudinal diffusion in bi-continuous chromatographic beds

We report on the possibility to extend to bi-continuous packings the two models for the effective longitudinal diffusion Deff, or B-term band broadening, recently proposed for discontinuous chromatographic beds. In bi-continuous packings, like monolithic columns, solutes experience a connected end-to-end pathway in both the mobile and stationary zones, as opposed to discontinuous packings, wherein the stationary adsorptive zone is distributed over a set of isolated elements. Since it is unclear whether a densely packed bed of spherical particles should be treated as a continuous or a bi-continuous medium, this extension is also crucial to fully understand the behaviour of packed particle beds. The proposed models for the effective longitudinal diffusion Deff originate from the adoption of the Two Zone Moment Analysis (TZMA) method by which Deff can be expressed as a linear combination of two essential quantities γm and γs, referred to as effective zone-diffusion factors. In the present work we propose two analytical models for γm and γs that now cover both the discontinuous and the bi-continuous case. To validate the theory, several bi-continuous packings are investigated, including the tetrahedral skeleton model (TSM), six different Triple Periodic Minimal Surface (TPMS) monoliths and randomly packed beds of spheres. For all of these, the models provide highly accurate results for Deff over a wide range of porosities and zone retention factors k″. The comparison with literature experimental data for both monolithic silica columns and columns packed with fully porous and porous-shell particles is also presented.

An azo-receptor immobilized mesoporous honeycomb silica framework as a solid-state chromogenic sensor for capturing ultra-trace cadmium ions from environmental/industrial samples

A solid-state naked-eye sensor composed of a mesoporous honeycomb structured silica monolith impregnated with a DMTHBD receptor offers a simple, rapid and eco-benign approach for the selective sensing of trace Cd2+, with brilliant color transitions.

Silica-based monoliths functionalized with DTPA for the removal of transition and lanthanide ions from aqueous solutions.

Transition and rare earth metals serve as indispensable raw materials across a broad spectrum of technological applications. However, their utilization is frequently linked to substantial waste production. Consequently, the recycling and recovery of these metals from end-of-life products or metal-contaminated aqueous environments hold significant importance within the framework of a circular economy. In our investigation, we employed synthetic mesoporous silica monoliths, synthesized via the sol-gel method and functionalized with chelating groups, for the efficient recovery of metal ions from aqueous matrices. The monoliths were characterized using a multi-technique approach and were tested in the recovery of paramagnetic Gd3+, Cu2+ and Co2+ ions from aqueous solutions, using 1H-NMR relaxometry to evaluate their uptake performance in real time and under simple conditions. Detailed information on the kinetics of the capture process was also highlighted. Finally, the possibility to regenerate the solid sorbents was evaluated.