Manufacturing toolbox for porous silica is good news for production of medicine

The chemical and pharmaceutical industry heavily relies on porous silica for the purification and conversion of raw materials into products. While silica materials with a range of different pore sizes are commercially available, a toolbox for large scale manufacturing that combines both flexibility and low cost, has thus far been lacking. Researchers from TU/e and Nouryon have developed a scalable strategy to synthesize silica microspheres with precisely tunable porosity and pore size. Their studies advance the understanding of microsphere assembly in emulsions and provide the next generation of tailor-made silica microspheres for use in purification applications and beyond. The results have been published in the leading journal Advanced Functional Materials.

Many natural substances such as rock, soil, or wood are porous and allow liquids to flow through them. In a similar fashion, but on a much smaller scale, porous silica is often used in the chemical industry to filter, separate and even (with the help of catalyst nanoparticles) convert raw materials into products.

To increase resource efficiency and purity of products, silica materials with a pore size and porosity that is optimized for a specific raw material and separation process are needed. However, large-scale manufacturing of porous silica technology have so far been limited in the range of achievable pore sizes and porosities.

Sol-Gel Emulsions

Porous silica can be made through a technology known as sol-gel emulsion technology. It uses silica particles in a water emulsion (so-called colloids) (sol) as building blocks to form a porous silica network – the gel. The benefits of making porous silica from nano particles are that no additional template molecules are needed to guide the formation of a porous network. The process can also easily be scaled up. Furthermore, a high level of control over the gelation reaction can be achieved via controlling sol concentration, acidity, temperature or addition of salts (ionic strength).

As the gelation reaction takes place in the confinement of a water in oil emulsion, special attention was given to the conditions inside the water droplets. Porous silica can be made by either shrinking the emulsion droplets (dewatering) under vacuum conditions (evaporation-driven assembly) or greatly increasing the reaction temperature in combination with high concentrations of salt (gelation-driven assembly).

By changing the size of the silica particles from 4 nm to 25 nm, the researchers were able to reach different but well-defined pore sizes of up to 40 nm. When mixing two types of silica mixtures any pore size between 4 and 50 nm could be made. In this way also porosity and pore size could be changed independently, which was not possible before.

“The new toolbox adds flexibility and reduces costs”, says Heiner Friedrich, who co-wrote the paper together with his colleague Remco Fijneman and others. “We expect our method to enable the next generation of tailor-made silica microspheres for use in purificaction, separation, catalysis and other applications”.

Development of drugs and medicine

One of the most promising applications of this technology is in the field of medicine and drug development, where separation and purification of molecules are a crucial step. This is commonly done using a technique called high-performance liquid chromatography (HPLC). The general principle of HPLC is simple: a fluid containing a mixture of molecules is passed through a fixed stationary bed consisting of porous silica microspheres and is separated into different fractions based on a difference in affinity between the molecules and the microspheres.

An important yet notoriously difficult class of molecules to separate are biomacromolecules such as peptides and antibodies, mainly due to their different sizes and diverse properties. Imagine a lock-and-key process. If the lock (the microsphere) and key (the molecule) do not fit, no efficient separation can take place. The silica microspheres produced by the researchers can be tuned specifically to the size and shape of the macromolecule of interest. This is much more efficient than conventional industrial processes, in which generic microspheres are produced from one sized building blocks, which then have to undergo multiple time-consuming post-treatment steps to tune the microsphere properties.

This research was done in collaboration with chemical company Nouryon.

Andreas J. Fijneman, Gijsbertus de With, Heiner Friedrich et al. Multiscale Colloidal Assembly of Silica Nanoparticles into Microspheres with Tunable Mesopores. Advanced Functional Materials. DOI: 10.1002/adfm.202002725.

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