Microfabricated airflow nozzle for microencapsulation of living cells into 150 micrometer microcapsules
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Microencapsulation of genetically engineered cells has attracted much attention as an alternative nonviral strategy to gene therapy. Though smaller microcapsules (i.e. less than 300 μm) theoretically have various advantages, technical limitations made it difficult to prove this notion. We have developed a novel microfabricated device, namely a micro-airflow-nozzle (MAN), to produce 100 to 300 μm alginate microcapsules with a narrow size distribution. The MAN is composed of a nozzle with a 60 μm internal diameter for an alginate solution channel and airflow channels next to the nozzle. An alginate solution extruded through the nozzle was sheared by the airflow. The resulting alginate droplets fell directly into a CaCl2 solution, and calcium alginate beads were formed. The device enabled us to successfully encapsulate living cells into 150 μm microcapsules, as well as control microcapsule size by simply changing the airflow rate. The encapsulated cells had a higher growth rate and greater secretion activity of marker protein in 150 μm microcapsules compared to larger microcapsules prepared by conventional methods because of their high diffusion efficiency and effective scaffold surface area. The advantages of smaller microcapsules offer new prospects for the advancement of microencapsulation technology.
KeywordsMaterial fabrication Cell encapsulation Microcapsule Size control Microfluidic device
We thank Mr. Y. Sando for helping with fabrication of the silicon plate. We also thank Kimica Corp. (Tokyo, Japan) for providing sodium alginate. This work was supported by the Nanotechnology Project, Ministry of Agriculture, Forestry and Fisheries, and the Program for Promotion of Fundamental Studies in Health Sciences of the Organization for Pharmaceutical Safety and Research of Japan.
- D. Chicheportiche and G. Reach, Diabetologia 31, 54 (1988).Google Scholar
- C. Dulieu, D. Poncelet, and R.J. Neufeld, in Encapsulation and Immobilization Techniques, edited by W.M. Kuhtreiber, R.P. Lanza and W.L. Chick (Birkhauser, Boston, 1999), p. 3.Google Scholar
- G. Hortelano, A. AlHendy, F.A. Ofosu, and P.L. Chang, Blood 87, 5095 (1996).Google Scholar
- K. Kuba, K. Matsumoto, K. Date, H. Shimura, M. Tanaka, and T. Nakamura, Cancer Res. 60, 6737 (2000).Google Scholar
- F.A. Leblond, G. Simard, N. Henley, B. Rocheleau, P.M. Huet, and J.P. Halle, Cell Transplant. 8, 327 (1999).Google Scholar
- R. Nir, R. Lamed, L. Gueta, and E. Sahar, Appl. Environ. Microbiol. 56, 2870 (1990).Google Scholar
- J. Schrezenmeir, L. Gero, C. Laue, J. Kirchgessner, A. Muller, A. Huls, R. Passmann, H.J. Hahn, L. Kunz, W. Mueller-Klieser, and et al., Transplant. Proc. 24, 2925 (1992).Google Scholar
- D. Tomioka, N. Maehara, K. Kuba, K. Mizumoto, M. Tanaka, K. Matsumoto, and T. Nakamura, Cancer Res. 61, 7518 (2001).Google Scholar