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Microfabricated airflow nozzle for microencapsulation of living cells into 150 micrometer microcapsules

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Abstract

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.

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Acknowledgments

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.

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Authors and Affiliations

  1. Food Engineering Division, National Food Research Institute, 2-1-12 Kannondai, Tsukuba, Ibaraki, 305-8642, Japan

    Shinji Sugiura & Mitsutoshi Nakajima

  2. Research Center of Advanced Bionics, National Institute of Advanced Industrial Science and Technology (AIST), Central 5th, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8565, Japan

    Shinji Sugiura

  3. Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan

    Tatsuya Oda, Yasuyuki Aoyagi, Ryota Matsuo, Tsuyoshi Enomoto & Nobuhiro Ohkohchi

  4. Division of Molecular Regenerative Medicine, Course of Advanced Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Japan

    Kunio Matsumoto & Toshikazu Nakamura

  5. Diagnostics Radiology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Mitsuo Satake

  6. Pathology Division, National Cancer Center Research Institute East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan

    Atsushi Ochiai

Authors
  1. Shinji Sugiura
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  2. Tatsuya Oda
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  3. Yasuyuki Aoyagi
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  4. Ryota Matsuo
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  5. Tsuyoshi Enomoto
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  6. Kunio Matsumoto
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  7. Toshikazu Nakamura
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  8. Mitsuo Satake
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  9. Atsushi Ochiai
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  10. Nobuhiro Ohkohchi
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  11. Mitsutoshi Nakajima
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Correspondence to Mitsutoshi Nakajima.

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Sugiura, S., Oda, T., Aoyagi, Y. et al. Microfabricated airflow nozzle for microencapsulation of living cells into 150 micrometer microcapsules. Biomed Microdevices 9, 91–99 (2007). https://doi.org/10.1007/s10544-006-9011-9

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  • DOI: https://doi.org/10.1007/s10544-006-9011-9

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