Alginate Microbeads Production

Microencapsulation is one of the most interesting fields in pharmaceutical technology since its inception many years ago. Microencapsulation products (microparticles, microbeads) are small entities that contain an active agent or core material surrounded by a shell or embedded into a matrix structure. [1] Among all these materials, alginate remains a suitable candidate for many applications. Alginate Microbeads are one of the most widely investigated cell encapsulation materials as they are biocompatible, non-toxic, biodegradable, and cost effective. [2]

Following is a method for encapsulation of reagent into alginate spheres with total control of bead formation. The generation is performed with the RayDrop developed and manufactured by Secoya, this droplet-based microfluidic method is used to precisely control the production of microbeads without the drawbacks of large size distribution found in other methods.

Secoya developed and manufactured the RayDrop used to perform this application note.

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Features of alginate microbeads production station

Complete system

The package contains all the necessary components  to begin generating alginate droplets.

Engineered solution

 The package contains accurate pressure controllers, microfluidic chips, and valves for the highest flexibility in terms of droplet size and generation rate.

Dedicated protocol

A protocol is available to assist you in setting up your experiments.

Customization possible

We can adapt the package to fulfil your needs (alginate microbeads size, generation rate) .

System setup

ALGINATE MICROBEADs generation setup

How to produce mono-dispersed alginate microbeads?

Microencapsulation is a technique by which solid, liquid, or gaseous active ingredients are packaged within a second material for the purpose of shielding the active ingredient from the surrounding environment. This technique has been employed in a diverse range of fields from chemicals and pharmaceuticals to cosmetics and printing.

Alginate is a natural polymer, extracted from seaweed, which is able to form a gel when dissolved in water and exposed to certain salts. The gelation reaction can be manipulated to create wet or dry spherical beads for visual effect, encapsulation of other materials or agglomeration of powders. Alginate microbeads are biodegradable, biocompatible, and non-toxic, which allows them to be used as drug delivery systems for controlled release of both hydrophobic and hydrophilic drugs.

Several methods and techniques are potentially useful for the preparation of polymeric microparticles in the broad field of microencapsulation, including extrusion, batch method or spray drying. The preparation method will determinate the type and the size of alginate microbead and influence the ability of the interaction among the components used in microbead formulations. Although there are multiple methods for the production, each presents numerous technical challenges, most commonly the high viscosity of the polymer fluids.

The critical design considerations of alginate microbeads are highly dependent on the applications. Among the considerations are the size, size distribution, shape, mass transport properties, biocompatibility, swelling properties, solubility, and mechanical and chemical stability. The carrier qualities can be influenced by the alginate composition and concentration, the presence of impurities, the type and concentration of gelling ions and non-gelling ions as well as the production process conditions.

The most popular way to produce mono-dispersed alginate microbeads is by using the dripping technique. In this method, the alginate solution is extruded through a capillary at a low volumetric rate and allowed to drip under gravity. Although this method has been used for many years, formation of the beads with desired size and spherical-shaped often requires some trial-and-error work on the liquid formulation and experimental set-up (e.g., solution viscosity or surface tension, tip size, collecting distance etc.). If the conditions are not optimum, deformed alginate beads or beads with tail could be produced, and this is a big limitation because in microbead production, particle size is key parameter.

As the reproducibility of such methods is low, there is demand for better techniques and control of the process to produce alginate microbeads.

Droplet-based microfluidics offers an efficient method for improvement of this process. It is a powerful tool which allows the production of micrometric monodispersed droplets, without the disadvantage of the irregular particle sizes of the other methods. Therefore, with microfluidics, it’s possible to have  more optimal control over the production and encapsulation process, reaching a higher monodispersity of microbeads than the other methods (extrusion methods, batch…). In addition, a higher reproducibility is obtained as it is a continuous (in-line) production.

ALGINATE MICROBEADs GENERATION PACK fluigent

Following is a method for encapsulation of reagent into alginate microbeads with total control of bead formation. The generation is performed with the RayDrop, a device developed and manufactured by Secoya. This droplet-based microfluidic method is used to precisely control the production of microbeads without the drawbacks of large size distribution common in other methods. The RayDrop is an emulsion generator based on the alignment of two capillaries immersed in pressure containing the continuous phase that controls the generation of alginate droplets. The dispersed phase exits one of the capillaries through a 3D printed nozzle placed in front of the extraction capillary for collecting the droplets. This particular geometry solves all wettability issues that sometimes appear in other microfluidic chips.

With the combination of the RayDrop device and Fluigent’s LineUP microfluidics pumps, Fluigent has developed an innovative system for the production of monodisperse alginate beads.

Conclusion

In this application note, we have demonstrated that using our setup, Fluigent was able to produce alginate microbeads with a dispersion in bead size lower than 2%. Microbeads of 95-160µm diameter are generated with standard RayDrop configuration (Nozzle of 30µm and outlet capillary 150µm) using alginate solution at 1% in water. By using the same procedure, other alginate concentrations, including 2%, which is frequently used in biological applications, have also been tested successfully. In this last case, a more viscous solution necessitates the use of tubing with a larger internal diameter. This set up and protocol can therefore be used to encapsulate bacteria, mammalian cells, and other reagents into alginate microbeads. We have successfully shown that using Fluigent products enables precise control over the production of high monodispersity alginate beads. As demonstrated, using the RayDrop with various nozzle sizes enables greater versatility. To target various droplet sizes, the user can easily change the capillary size.

alginate MICROBEADs generation chip
alginate MICROBEADs generation
alginate MICROBEADs generation monodispercity
alginate MICROBEADs production high monodispercity

References

[1] Obeidat, W. M. (2009). Recent Patents Review in Microencapsulation of Pharmaceuticals Using the Emulsion Solvent Removal Methods, 178–192.

[2] Andersen, Therese & Strand, Berit & Formo, K. & Alsberg, Eben & Christensen, B.E.. (2011). Alginates as biomaterials in tissue engineering. Carbohydrate Chemistry. 37. 227-258. 10.1039/9781849732765-00227.

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