Leading device for controlled encapsulation of cells, biological and active materials for labscale R&D work. Sophisticated technique enables particle production for application in numerous biotechnology and medical processes and other fields, requiring sterile conditions. View more
The sterile bead and capsule producer
Benefits

Sterile process

  • Fully autoclavable production system (reaction vessel) enables obtainment of a completely sterile environment, if required
  • Sterile delivery and removal of materials and final product due to innovative design
  • Operate under a laminar flow cabinet in open mode (no reaction vessel)
  • Possibility to integrate into a GMP process

Proven performance

  • Encapsulation of cells and biological material (enzymes, proteins, organelles etc.) under very mild and physiological conditions
  • Reproducible and continuous results
  • Viability and stability of cells and biological material is maintained throughout process
  • Production of a wide range of particle sizes (150 μm - 4 mm): 8 nozzle sizes available
  • Production of homogenous structures with a very narrow size distribution (≤ 1.5%)

Easy to use

  • Fast installation with a quick and intuitive operation and simple maintenance
  • Application booklet and database enables rapid obtainment of production parameters
  • Quick optimization due to visualization of the production process and real-time control
  • Small dimensions enables easy handling and movement
Features
Encapsulator B-390 single nozzle

Set of 8 single nozzles

0.08, 0.12, 0.15, 0.2, 0.3, 0.45, 0.75 and 1.0 mm, Stainless steel 316
Concentric Nozzle Set

Concentric nozzle set

One step core/shell capsule production

Encapsulator B-395 Pro reaction vessel

Reaction vessel

  • 2 liter working volume
  • Autoclavable
  • GMP compliant surface treatment of stainless steel
Expert Advice

What influences the final bead size?

Bead size is influenced by following parameters:
  • Nozzle size - major influence
  • Liquid flow rate - moderate influence
  • Vibration frequency - moderate influence
  • Physico-chemical properties of the encapsulation mixture - minor influence.
The most important parameter for bead production is the nozzle size. In general final bead diameter is about twice the size of the nozzle aperture.

What influences final capsule size?

Capsule size is influenced by the following parameters:
  • Shell (external) nozzle size - major influence
  • Core (internal) nozzle size – moderate influence
  • Liquid flow rate for shell - moderate influence
  • Liquid flow rate for core material – minor influence
  • Vibration frequency - moderate influence
  • Physico-chemical properties of the encapsulation mixture - minor influence.
The most important parameter for capsule production is the size of the shell nozzle. In general final capsule diameter is about twice the size of the shell nozzle aperture. What influences the core size within core-shell capsules.

How is the core size influnced?

  • Shell (external) nozzle size - minor influence
  • Core (internal) nozzle size – major influence
  • Liquid flow rate for shell - minor influence
  • Liquid flow rate for core material – major influence
  • Vibration frequency - moderate influence
  • Physico-chemical properties of the encapsulation mixture - minor influence.
The most important parameter for core size within capsules is the size of the core nozzle and the flow rate of the core material. In general final core diameter within capsules is about 1-2.5 times the size of the core nozzle aperture with increasing with increasing flow rates resulting in larger diameters.

Is scale up of the process possible and how can it be achieved?

Scale up is simply done by multiplying the number of nozzles on the machine, and is referred to as the multi-nozzle system. The parameters used for the one nozzle system should also apply to the multi-nozzle system. Therefore a special scale-up development is not required. However the process must work and be stable when using the one nozzle system before switching to a multi-nozzle system: Buchi offers such a multi-nozzle system which enables between 1 and 6 nozzles to be operated simultaneously by the operator.

What is the optimal frequency and amplitude range to work within for different nozzle size?

The optimal frequency and amplitude ranges for different nozzle sizes are given in the following table.  
  • Nozzle Diameter : 1.0 mm          Frequency Range: 40 to 200 Hz      Amplitude Range: 6 to 9
  • Nozzle Diameter : 750 microns  Frequency Range: 40 to 300 Hz       Amplitude Range: 5 to 9
  • Nozzle Diameter : 500 microns  Frequency Range: 100 to 400 Hz     Amplitude Range: 2 to 5
  • Nozzle Diameter : 400 microns  Frequency Range: 200 to 500 Hz     Amplitude Range: 1 to 4
  • Nozzle Diameter : 300 microns  Frequency Range: 400 to 800 Hz     Amplitude Range: 1 to 3
  • Nozzle Diameter : 200 microns  Frequency Range: 600 to 1200 Hz   Amplitude Range: 1 to 3
  • Nozzle Diameter : 150 microns  Frequency Range: 800 to 1800 Hz   Amplitude Range: 1 to 4
  • Nozzle Diameter : 80 microns    Frequency Range: 1300 to 3000 Hz Amplitude Range: 4 to 4

What effect(s) does the viscosity of the encapsulation mixture have on the process parameters?

The viscosity of the encapsulation mixture has the following effects:
  • The higher the viscosity the higher the minimal jet velocity
  • The higher the viscosity the higher the working flow rate
  • The higher the viscosity the lower the optimal frequency
  • The higher the viscosity the larger the beads/capsules

What types of polymers can be used to produce the bead structure and how is a polymer selected?

A range of natural and synthetic polymers are commercial available either from Buchi or chemical suppliers. Some of the common materials are follows:
  • Natural polymers: Na-Alginate, Gelatin, lamda-Carragennan, Agar, Agrose, Chitosan, Cellulose, Whey protein, Collagen, Pectin
  • Synethtic polymers: Polyacrylamide, Polyvinyl Alcohol (PVA), poly(lactic-co-glycolic acid) (PLGA), Cellulose sulphate, polyDADMAC, poly-l-lysine, Polyethylene Glycol (PEG)
  • In additional  range of waxes can also be used to produce the capsules

What type of alginate should be used?

Alginate is a natural polymer deviated from the cell wall of various different seaweed plants. On account of its natural origin the type of alginate supplied by different suppliers can vary extensively and this variable composition can have a negative effect on the quality of the alginate. This can result in the production of low quality particles or in some cases beads/capsules cannot be produced, while it also affects reproducibility of experiments. Buchi now supplies high quality alginate with a consistent composition. Each batch of alginate is pre-tested by scientists at Buchi to ensure customers can consistently produce high quality beads/capsules in a reproducible manner.

Polymer solution cannot be pumped through the nozzle and bead producing unit. What can I do?

In this case either the nozzle or the bead producing unit is blocked with dried polymer. Cleaning nozzle: See nozzle cleaning section
  • Cleaning bead production unit: If alginate is being used, soak the unit in 0.1 M NaOH for 1 hour and then pump the NaOH through the unit using a syringe pump or place the unit within a sonication bath for 1 – 5 minutes to loosen the alginate. For gelatin either soak in hot water (> 60 °C) and flush or sonication as above.
  • For most materials, sonication will help to unblock it and the unit should be flushed with a liquid with can dissolve the entrapped material i.e. for PGLA this can be dichloromethane.
  • Blocking of the pre-filter in the producing unit can also prevent the pumping of the polymer material through the bead producing unit and should be changed. See YouTube videos for more details.