'Producing high-quality microcapsules opens doors to new applications'

| Hans Wolkers

Scientists from the Engineering Fluid Dynamics group at the University of Twente have succeeded in efficiently producing uniform-sized microcapsules. These capsules have many important applications, including controlled drug delivery. Their finding was published as cover article last January in Advanced Materials.

'Making high-quality microcapsules is one of the most important results of our research,’ Assistant Professor Jieke Jiang says. The capsules consist of a liquid core and a protective shell surrounded by a layer of air. Ultrasonic sound can break this layer, releasing the contents. This has many applications in food, pharmaceuticals and biotechnology. He holds a glass bottle, containing an opaque, whitish fluid with a transparent layer on top. ‘This liquid is actually oil containing millions of tiny microcapsules of very similar size.’ Together with his colleague, Associate Professor Claas-Willem Visser, he developed a state-of-the-art method to produce large amounts of such microcapsules for different purposes. ‘Producing such high-quality microcapsules, is quite an achievement’ Visser says. ‘It opens doors to many new applications, for example capturing CO2 and transport it inside these capsules to places where it is needed, for example, greenhouses.’

Protect medication

Microcapsules are small spheres, usually at the micrometer scale, consisting of a liquid core, surrounded by a protective, outer shell. This outer shell often is water-soluble or hydrophilic, and may consist of a variety of materials, like gelatin or nanoparticles with specific properties. The composition and properties of the outer shell determine the protection and eventual release of the liquid core. Many industries apply these microcapsules in their products. For example, the food industry may encapsulate edible dyes, aromatics, minerals and vitamins to protect these substances from degradation (oxidation) and extend shelf life. Also, pharmaceutical companies apply microcapsules to stabilize and protect medication, before and after administration. Subsequent breakage of the shell allows for a controlled and steady release of the active ingredient into the patient.

A special type of microcapsule consists of a water droplet, coated with a water-repellent shell, and is called dry water. It has special applications, for example, they may be used to improve hydrating properties in cosmetics, but also for storing gas. In addition, dry water may be transformed into so-called anti-bubbles: water-repellant capsules surrounded with a thin air layer, that are placed into water. Ultrasound may disrupt the air-surrounded shell in a controlled way, thereby releasing dissolved active ingredients in the core. This offers great potential for controlled and precisely timed drug delivery at a specific location, for example inside a tumor.

Complicated production

However, despite their broad applications, producing large volumes of high-quality, similarly-sized microcapsules with an aqueous core and a water-repellant shell, is still challenging. ‘One quite complicated production method for these capsules uses so-called microfluidic chips, where micro tunnels are etched into the chip’, Claas-Willem Visser explains. Visser is Associate Professor at the Engineering Fluid Dynamics Group. ‘Leading fluids through these tiny tunnels in a very controlled way, forms the basis for production of microcapsule of similar size, but at an extremely slow rate. It takes over a month to fill a single coffee beaker.’ Therefore, they are only applied for high-quality applications. A much quicker and cheaper way to fabricate capsules involves a system where the core liquid is mechanically mixed with a suspension of nanoparticles or a solution of polymers. These nanoparticles eventually form the outer shell. However, although the production rate of microcapsules is very high, their size and shape cannot be controlled, and much material is wasted in the process. Therefore, the team was looking for a more efficient method that could produce similar-sized microcapsules more quickly.

High throughput
The eureka moment came when one of the scientists observed that by ejecting a powerful stream of fluid through a layer of a nanoparticles suspension resulted in the formation of the desired microcapsules. The stream of liquid eventually formed the capsule’s aqueous core, while the nanoparticle layer, made up the outer shell. The principle of this method is quite simple: with a gently flowing top layer of a nanoparticle suspension, a vibrating nozzle forcefully ejects the liquid through this top layer and drags a coating of the nanoparticle suspension along with it. As the nozzle that ejects the liquid jet is vibrating, the liquid jet stream breaks up into tiny, individual droplets that all have an equal size. The nanoparticle suspension subsequently forms a coating around the droplets. Ultimately, the system formed microcapsules with a thin solid wall, consisting of nanoparticles and a water-containing core. An important finding was that the liquid jet stream must be much thinner than the liquid it is ejected through, to prevent clogging of the jet mouth by the nanoparticles in the coating liquid.


Initially, the layer of nanoparticles around the new droplet is unsolidified and therefore unstable. ‘We stabilized the droplets by collecting them in a hot oil bath to achieve rapid solidification’, Jiang says. ‘The suspension liquid, that is still present in the nanolayer outer shell, will now diffuse into the oil bath, and the nanoparticles will solidify, forming a firm shell.’ After the shell has hardened, the oil can be removed and the newly formed capsules are dried, forming the dry water. The method generates a continuous supply of microcapsules and is more than 100 times quicker than the micro-fluidic chip method, with similarly high quality of the microcapsules. In addition, a wider spectrum of possible shell materials can be used, enabling tailored applications for a variety of industries.

Many applications
As an icing on the cake, these ‘dry water’ microcapsules can be transformed into so-called anti-bubbles. ‘Due to the water-repellant coating, these capsules are simultaneously coated with a thin air layer, and form an anti-bubble when they are submerged into water’, Jiang explains. ‘A normal bubble has air inside, surrounded by a liquid shell, and air outside. An anti-bubble is exactly the opposite: they contain liquid inside, surrounded by air and liquid outside.’ The air layer gives the capsule contents extra protection against leakage, making it last for days. At any given moment, the shell might be broken using ultrasound, releasing the contents. Since the method allows for anti-bubble production in large quantities, with consistently high quality, there are many uses. For example, they are very suitable for controlled release of medication: once anti-bubbles have reached their target site, for example a tumor, made visible by low-intensity ultrasound, a higher ultrasound intensity may break the shell releasing the medication.

Big advantage

But there are more applications. Since the new method is very suitable to eject suspensions containing a lot of solid particles, it can also be applied to print such dense suspensions with significantly reduced risk of nozzle clogging. That’s a big advantage as clogging is a common problem faced by many applications and it wastes energy and materials and cause delays in producing products.  Jiang: ‘Additionally, our method enables 3D printing of new and complex materials, including foam-resembling solid structures with ceramic walls. Many of these materials are bio-sourced or biocompatible. These new materials open new doors in bio-engineering, acoustics, and sensing, at reasonable cost and low environmental impact.’ 

The work has been published as: Jiang, J., Poortinga, A.T., Liao, Y., Kamperman, T., Venner, C.H. and Visser, C.W., 2023. High‐Throughput Fabrication of Size‐Controlled Pickering Emulsions, Colloidosomes and Air‐Coated Particles via Clog‐Free Jetting of Suspensions. Advanced Materials, p.2208894, https://doi.org/10.1002/adma.202208894

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