CASE
STUDY

Extrusion dripping
generating Hydrogel
beads

July 2022
Author:Florian Siemenroth

Case study: Extrusion dripping generating Hydrogel beads
July 2022

Encapsulating bioactive
agentsEmulation of bioactive
components

Hydrogel beads is a widely known technology in pharmaceutical or cosmetic development andproduction. The task of theses droplets is to encapsulate bioactive reagents in stable spheres. Later,
they release that material at defined working points on the patient or consumer end.
This case study shall share the idea of generating alginate beads utilizing a microfluidic pressure
driven flow setup based on piezo electric micropumps.

What is microfluidics?
Microfluidics is the fine art of creation and manipulation of small portions of fluids, often realized by flow
within small, sub-millimetre-scale channels. These small dimensions allow the fluid flow to be controlledwith exquisite precision (Seifert, Thiele; 2020).

About the mp6 micropump
The available, industrialized and commercialized example is the mp6 micropump by Bartels MikrotechnikGmbH. This micro pump is a positive displacement membrane pump utilizing piezo buzzers. The alternating
displacement of the piezo acutators lead to the following typical fluidic values of the pump:▪
▪

Liquids (eta = 1 mPas): q = 5 - 8000 µl/min in free flow and p > 600 mbar
Gas: q > 25 ml/min in free flow and p > 150 mbar

Introduction
Hydrogel microparticles are well-known and often utilized in pharmaceutical applications or the food andbeverage industry. They are usually used as a matrix to encapsulate biological and chemical reagents likedrugs, proteins or cells for diagnostics, bioreactors or medical treatment. Also, due to its size, shape,deformability and mechanical properties, hydrogel particles are often used to emulate biologicalcomponents like cells.
All values are approximate and no guarantee of specific technical properties.
Changes in the course of technical progress are possible without notice.

Case study: Extrusion dripping generating Hydrogel beads
July 2022
Standard, accessible materials for hydrogels are biopolymers e.g., gelatin, agarose, alginate, pectin, etc.
Alginate is a preferred material because of its low cost, non-toxicity and the simple methods for thecrosslinking options. There are many production procedures, such as emulsification, extrusion dripping or
droplet generation by flow focusing or T-junction in microfluidic chips.

I. Alginate hydrogel microparticles
Typical or beneficial Alginate hydrogel characteristics are mainly based on their hydrophilic polymeric
networks. The networks can absorb and retain a huge amount of water within the structure and it isgenerated by polymer crosslinking. There are mainly four different cross-linking options, such as ionic, Hbonding, hydrophobic covalent and vor covalent.

II. Extrusion Dripping
The extrusion dripping method is based on the pendant drop method. The force between a fluid and anozzle or tubing depends on the diameter d of the nozzle and the surface tension 𝛾 of the fluid.
𝐹𝛾 = 𝜋𝑑𝛾
Equating this with gravity generates the link to the mass of the droplet.
𝑚𝑔 = 𝜋𝑑𝛾
Idealizing the shape as spheroid and including the fluid’s density 𝜌 one can calculate the radius r of thedroplet.
4𝜋𝑟 3 𝑔= 𝜋𝑑𝛾3𝜌III. Experiment
For the alginate beads production, a microfluidic pressure driven flow setup is used within the experiments
as shown in figure 1. The setup consists of four mp6 micropumps, two in a series setup for an increased
pressure and two of those series setups in parallel for an increased flow rate. Now the pressure is generated
in Fluid Reservoir 1, which contains Alginate in a liquid form. The liquid is transported to the nozzle where
the droplets are generated. Falling into Fluid Reservoir 2, which contains a Ca2+-solution, the cross-linking
takes place and Alginate beads are generated as solid spheroids. Changing the diameter of the nozzle leads
to different Alginate bead sizes. As shown in figures 3 and 4.

Figure 1 Sketch of experimental setup
All values are approximate and no guarantee of specific technical properties.
Changes in the course of technical progress are possible without notice.

Case study: Extrusion dripping generating Hydrogel beads
July 2022

Alginate droplets
4Diametre [mm]3,532,52
1,510,50Droplets

Nozzle ID

Figure 2 Alginate droplets compared to nozzle diameters

Figure 3 Generated Alginate beads; From left to right: 3.75 mm, 3 mm, 2.6 mm, 2.5 mm in diameterAs a conclusion, a microfluidic pressure driven flow system in combination with the correct selection ofnozzle diameters can be a very powerful tool for generating alginate beads of different sizes in high batches
decreasing development and production efforts. Due to its small system size the alginate bead generation
can take place at the point of need.

Components and systems used:••••

mp6 micropump by Bartels Mikrotechnik
mp-Multiboard2 incl. mp-Highdriver4 by Bartels Mikrotechnik
Pressurized reservoir
Dispensing nozzle with different diameterAll values are approximate and no guarantee of specific technical properties.
Changes in the course of technical progress are possible without notice.

Case study: Extrusion dripping generating Hydrogel beads
July 2022

Bartels Mikrotechnik is a globally active manufacturer and development service provider inthe field of microfluidics. In the microEngineering division, the company supports industrial
customers in the modification, adaptation and new development of high-performance andmarket-oriented product solutions through the innovative means of microsystems technology.
The second division, microComponents, produces and distributes microfluidic products andsystems, especially for miniaturized and portable applications. Our key products aremicropumps that convey smallest quantities of gases or liquids and are used in a variety ofways in biotechnology, pharmaceuticals, medical technology and numerous other applications.
Bartels Mikrotechnik with passion for microfluidics!

Follow Bartels:

Contact us:
Bartels Mikrotechnik GmbH
Konrad-Adenauer-Allee 1144263 Dortmund Germany

www.bartels-mikrotechnik.de
info@bartels-mikrotechnik.de
Tel: +49-231-47730-500

All values are approximate and no guarantee of specific technical properties.
Changes in the course of technical progress are possible without notice.