Quality-by-Design Approach to Process Intensification of Bioinspired Silica Synthesis.

Characterizing nanomaterials is challenging due to their macromolecular nature, requiring suites of physicochemical analysis to fully resolve their structure. As such, their synthesis and scale-up are notoriously complex, especially when compared to small molecules or bulk crystalline materials, which can be provided a unique fingerprint from nuclear magnetic resonance (NMR) or X-ray diffraction (XRD) alone. In this study, we address this challenge by adopting a three-step quality-by-design (QbD) approach to the scale-up of bioinspired silica nanomaterials, demonstrating its utility toward synthesis scale-up and intensification for this class of materials in general. First, we identified material-specific surface area, pore-size distribution, and reaction yield as critical quality attributes (CQAs) that could be precisely measured and controlled by changing reaction conditions. We then identified the critical process parameters (CPPs) controlling bioinspired synthesis properties, exploring different process routes, incorporating commercial reagents, and optimizing reagent ratios, comparing silica properties against original CQA values to identify acceptable limits to each CPP. Finally, we intensified the synthesis by increasing reagent concentration while simultaneously incorporating the optimized CPPs, thereby modifying the bioinspired silica synthesis to make it compatible with existing manufacturing methods. We increased the specific yield from ca. 1.1 to 38 g/L and reduced the additive intensity from ca. 1 to 0.04 g/g product, greatly reducing both synthesis cost and waste production. These results identify a need for mapping the effects of critical process parameters on material formation pathways and CQAs to enable accelerated scale-up and transition from the lab to the market.

Identifying pathways to metal-organic framework collapse during solvent activation with molecular simulations.

Metal-organic framework (MOF) materials are a vast family of nanoporous solids with potential applications ranging from drug delivery to environmental remediation. Application of MOFs in these scenarios is hindered, however, by difficulties in MOF 'activation' after initial synthesis - removal of the synthesis solvent from the pores to make the pore space accessible - often leading to framework collapse if improperly performed. While experimental studies have correlated collapse to specific solvent properties and conditions, the mechanism of activation-collapse is currently unknown. Developing this understanding would enable researchers to create better activation protocols for MOFs, accelerating discovery and process intensification. To achieve this goal, we simulated solvent removal using grand-canonical Monte Carlo and free energy perturbation methods. By framing activation as a fluid desorption problem, we investigated activation processes in the isoreticular metal organic framework (IRMOF) family of MOFs for different solvents. We identified two pathways for solvent activation - the solvent either desorbs uniformly from each individual pore or forms coexisting phases during desorption. These mesophases in turn lead to large capillary stresses within the framework, corroborating experimental hypotheses for the cause of activation-collapse. Finally, we found that the activation energy of solvent removal increased with pore size and connectivity due to the increased stability of solvent mesophases, matching experimental findings. Using these simulations, it is possible to screen MOF activation procedures, enabling rapid identification of ideal solvents and conditions and thus enabling faster development of MOFs for practical applications.

Mimicking Biosintering: The Identification of Highly Condensed Surfaces in Bioinspired Silica Materials.

Interfacial interactions between inorganic surfaces and organic additives are vital to develop new complex nanomaterials. Learning from biosilica materials, composite nanostructures have been developed, which exploit the strength and directionality of specific polyamine additive-silica surface interactions. Previous interpretations of these interactions are almost universally based on interfacial charge matching and/or hydrogen bonding. In this study, we analyzed the surface chemistry of bioinspired silica (BIS) materials using solid-state nuclear magnetic resonance (NMR) spectroscopy as a function of the organic additive concentration. We found significant additional association between the additives and fully condensed (Q4) silicon species compared to industrial silica materials, leading to more overall Q4 concentration and higher hydrothermal stability, despite BIS having a shorter synthesis time. We posit that the polyfunctionality and catalytic activity of additives in the BIS synthesis lead to both of these surface phenomena, contrasting previous studies on monofunctional surfactants used in most other artificial templated silica syntheses. From this, we propose that additive polyfunctionality can be used to generate tailored artificial surfaces in situ and provide insights into the process of biosintering in biosilica systems, highlighting the need for more in-depth simulations on interfacial interactions at silica surfaces.

Preparation of Functional Silica Using a Bioinspired Method.

The goal of the protocols described herein is to synthesize bioinspired silica materials, perform enzyme encapsulation therein, and partially or totally purify the same by acid elution. By combining sodium silicate with a polyfunctional bioinspired additive, silica is rapidly formed at ambient conditions upon neutralization. The effect of neutralization rate and biomolecule addition point on silica yield are investigated, and biomolecule immobilization efficiency is reported for varying addition point. In contrast to other porous silica synthesis methods, it is shown that the mild conditions required for bioinspired silica synthesis are fully compatible with the encapsulation of delicate biomolecules. Additionally, mild conditions are used across all synthesis and modification steps, making bioinspired silica a promising target for the scale-up and commercialization as both a bare material and active support medium. The synthesis is shown to be highly sensitive to conditions, i.e., the neutralization rate and final synthesis pH, however tight control over these parameters is demonstrated through the use of auto titration methods, leading to high reproducibility in reaction progression pathway and yield. Therefore, bioinspired silica is an excellent active material support choice, showing versatility towards many current applications, not limited to those demonstrated here, and potency in future applications.

An Eco-Friendly, Tunable and Scalable Method for Producing Porous Functional Nanomaterials Designed Using Molecular Interactions.

Despite significant improvements in the synthesis of templated silica materials, post-synthesis purification remains highly expensive and renders the materials industrially unviable. In this study this issue is addressed for porous bioinspired silica by developing a rapid room-temperature solution method for complete extraction of organic additives. Using elemental analysis and N2 and CO2 adsorption, the ability to both purify and controllably tailor the composition, porosity and surface chemistry of bioinspired silica in a single step is demonstrated. For the first time the extraction is modelled using molecular dynamics, revealing that the removal mechanism is dominated by surface-charge interactions. This is extended to other additive chemistry, leading to a wider applicability of the method to other materials. Finally the environmental benefits of the new method are estimated and compared with previous purification techniques, demonstrating significant improvements in sustainability.