High-Throughput Methods for Miniaturization of Implantable Artificial Cells

Document Type

Book Chapter

Publication Date



Imperial College Press


Using three different fabrication methods, namely Electrostatic Spraying, On-Chip Synthesis and Inkjet Bio-Printing, miniaturization of alginatebased microcapsules ranging from 20–100 μm has been achieved. With a limited amount of published cell and drug-delivery data, the projected therapeutic applications differ by miniaturization technique, dependent in turn on the starting alginate concentration. The capsules miniaturized using the On-Chip Synthesis method would be ideal for implantation in tumors in non-invasive drug delivery applications. As for the other two methods with documented cell encapsulation feasibility, the benefits would be in the areas of programmed cell delivery, metabolic disorders and wider bio-membrane porosity studies. The effect of miniaturization on the strength, porosity and permeability of alginate capsules using Inkjet Bio-Printing with a throughput of 1.8 × 106 microcapsules/hr are the following: (1) Strength has been enhanced by a higher degree of cross-linking, thickening the cross-linking solution or subsequent coating steps as shown by results of spectrophotometric measurements; (2) Neither porosity nor the reflection coefficients have been affected for blue dextran (MW = 2000 kDa) and FITC dextran (MW = 4 kDa), as shown by results of Atomic Force Microscopy measurements of pore sizes; and (3) Permeability has been enhanced as a result of miniaturization when comparing standard 1000 μm macrocapsules (1.5% MV alginate cross-linked with 1.5% CaCl2) to 30 μm minicapsules (0.5% LV alginate cross-linked with 15% CaCl2 and coated with 0.5% chitosan) as shown by results of the Fluorescence Microscopy measurements. In light of these preliminary findings, the hypothesis of diffusion across the membrane being inversely correlatedto the surface to volume ratio (S/V) has been confirmed for artificial cell miniaturization, and the membrane strength and porosity can be tuned for a wide array of promising applications in cutting-edge areas of nanomedicine.


Thomas Ming Swi Chang