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A three-dimensional microfluidic approach to scaling up microencapsulation of cells

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Abstract

Current applications of the microencapsulation technique include the use of encapsulated islet cells to treat Type 1 diabetes, and encapsulated hepatocytes for providing temporary but adequate metabolic support to allow spontaneous liver regeneration, or as a bridge to liver transplantation for patients with chronic liver disease. Also, microcapsules can be used for controlled delivery of therapeutic drugs. The two most widely used devices for microencapsulation are the air-syringe pump droplet generator and the electrostatic bead generator, each of which is fitted with a single needle through which droplets of cells suspended in alginate solution are produced and cross-linked into microbeads. A major drawback in the design of these instruments is that they are incapable of producing sufficient numbers of microcapsules in a short-time period to permit mass production of encapsulated and viable cells for transplantation in large animals and humans. We present in this paper a microfluidic approach to scaling up cell and protein encapsulations. The microfluidic chip consists of a 3D air supply and multi-nozzle outlet for microcapsule generation. It has one alginate inlet and one compressed air intlet. The outlet has 8 nozzles, each having 380 micrometers inner diameter, which produce hydrogel microspheres ranging from 500 to 700 μm in diameter. These nozzles are concentrically surrounded by air nozzles with 2 mm inner diameter. There are two tubes connected at the top to allow the air to escape as the alginate solution fills up the chamber. A variable flow pump 115 V is used to pump alginate solution and Tygon® tubing is used to connect in-house air supply to the air channel and peristaltic/syringe pump to the alginate chamber. A pressure regulator is used to control the flow rate of air. We have encapsulated islets and proteins with this high throughput device, which is expected to improve product quality control in microencapsulation of cells, and hence the outcome of their transplantation.

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Acknowledgements

The authors acknowledge the financial support of the National Institutes of Health (GRANT # RO1DK080897), the Rosenfeld Estate, Greenville, NC for research in Dr. Opara’s laboratory and the National Science Foundation IR/D Program for providing travel support for Dr. M. K. Ramasubramanian to direct the research at North Carolina State University. Any opinion, findings, and conclusions or recommendations expressed in this material are those of the authors and not necessarily reflect the views of the funding organizations.

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Authors and Affiliations

  1. Department of Mechanical & Aerospace Engineering, North Carolina State University, Raleigh, NC, USA

    Sameer Tendulkar & Melur K. Ramasubramanian

  2. Biomedical Engineering, North Carolina State University, Raleigh, NC, USA

    Melur K. Ramasubramanian

  3. Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC, USA

    Sayed-Hadi Mirmalek-Sani, Charles Childers, Justin Saul & Emmanuel C. Opara

  4. School of Biomedical Engineering & Sciences, Wake Forest University Health Sciences, Winston-Salem, NC, USA

    Justin Saul & Emmanuel C. Opara

  5. Department of Mechanical & Aerospace Engineering, North Carolina State University, Engineering Bldg III, Campus Box 7910, 911 Oval Drive, Raleigh, NC, 27695-7910, USA

    Melur K. Ramasubramanian

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  1. Sameer Tendulkar
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  2. Sayed-Hadi Mirmalek-Sani
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  3. Charles Childers
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  4. Justin Saul
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  5. Emmanuel C. Opara
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  6. Melur K. Ramasubramanian
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Correspondence to Melur K. Ramasubramanian.

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Tendulkar, S., Mirmalek-Sani, SH., Childers, C. et al. A three-dimensional microfluidic approach to scaling up microencapsulation of cells. Biomed Microdevices 14, 461–469 (2012). https://doi.org/10.1007/s10544-011-9623-6

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