Introduction


Cell encapsulation is a new and powerful possibility in research and development as well as for production processes. Our Encapsulators fulfil the high requirements of animal cell encapsulation e.g.
  • bead size < 1 mm
  • low shear stress
  • narrow bead size distribution
  • batch to batch consistency
  • short production time
  • sterile working conditions.

The bead production technology is based on the principle that a laminar liquid jet is broken into equally sized droplets by a superimposed vibration.
In the late 19th century, Lord Rayleigh theoretically analyzed the instability of liquid jets. He showed that the frequency for maximum instability is related to the velocity of the jet and the nozzle orifice. The bead diameter is approximately twice the diameter of the nozzle orifice.

 

The optimal vibration parameters are determined in real time in the light of the incorporated stroboscope. Once determined, the parameters are easily reset in the future, making the process highly reproducible.
The bead diameter can be set between 0.15 to 2 mm.


Schematic Description and Principal of Operation of the Encapsulator BIOTECH

 

The product to be encapsulated (cells, microorganisms, or other biologicals and chemicals) is mixed with an encapsulating polymer (typically alginate) and the mixture put into a syringe (1) or a pressure bottle (2), see figure below. The polymer-product mixture is forced into the pulsation chamber (3) by either a syringe pump (S) or by air pressure (P). The liquid then passes through a precisely drilled nozzle (5) and separates into equal size droplets on exiting the nozzle. These droplets pass through an electrical field between the nozzle (5) and the electrode (6) resulting in a surface charge. Electrostatic repulsion forces disperse the beads as they drop to the hardening solution.

 

Optimal parameters for bead formation are indicated by visualization of real-time bead formation in the light of a stroboscope lamp (13). When optimal parameters are reached, a standing chain of droplets is clearly visible. Once established, the optimal parameters can be preset for subsequent bead production runs with the same encapsulating polymer-product mixture. Poorly formed beads, which occur at the beginning and end of production runs, are intercepted by the bead bypass collection cup (8).

 

Depending on several variables, 50 – 3000 beads are generated per second and collected in a hardening solution within the reaction vessel (7). Solutions in the reaction vessel are continuously mixed by a magnetic stir bar (M) to prevent bead clumping. At the conclusion of the production run, the hardening solution is drained off (waste port), while the beads are retained by a filtration grid (14). Washing solutions, or other reaction solutions, are added aseptically through a sterile filter (9). The beads can be further processed into microcapsules, or transferred to the bead collection flask (15).

 

  1)

Syringe

  2)

Pressure bottle

  3)

Pulsation chamber

  4)

Vibration system

  5)

Nozzle

  6)

Electrode

  7)

Reaction vessel

  8)

Bypass-cup

  9)

Liquid filter

10)

Air filter

11)

Electrostatic charge generator

12)

Frequency generator

13)

Stroboscope

14)

Filtration grid

15)

Bead collection flask

 M)

Magnetic stirrer

 P)

Pressure control system

 S)

Syringe pump