Upscaling the production of microencapsulated pancreatic islets.

Presently used single-needle air-driven droplet generators are incapable of producing sufficient numbers of islet-containing droplets in a sufficiently short time-period to allow for successfully grafting alginate-poly-L-lysine encapsulated islets in large animals or humans. We have designed an air-driven multineedle droplet generator, which increases the production rate by simultaneously producing multiple droplets. Although we have tested a four-needle device, the construction is such that the number of needles, and thereby the production rate, can be readily extended. The production rate can be further extended by increasing the number of islets per millilitre alginate in the reservoir. When tested with 500 and 800 microm capsules, an increase in the number of islets per millilitre alginate was found to be associated with an increase in the number of inadequately encapsulated islets in a diameter-dependent fashion. When small instead of large capsules are produced from a given volume of alginate, larger numbers of capsules are obtained, but also a larger portion of inadequate capsules. With 10,000 islets per millimetre alginate, these combined effects can be calculated to result in a two-fold increase in the production rate of adequate capsules when 500 microm instead of 800 microm capsules are produced. Hence, substantial upscaling of the production can be achieved by combining an increase in the number of needles with a decrease in the capsule diameter.