Spiral-shaped inertial stem cell device for high-throughput enrichment of iPSC-derived neural stem cells

Abstract

Stem cell enrichment plays a critical role in both research and clinical applications. The typical method for stem cell enrichment may use invasive processes and takes a long period of time. Spiral-shaped microfluidic devices, which combine lift and Dean drag forces to direct cells of different sizes into separate trajectories, can be used to noninvasively process samples at a rate of milliliters per minute. This paper presents a simple 2-loop spiral-shaped inertial microfluidic devices with the aid of sheath flow to enrich neural stem cells (NSCs), derived from induced pluripotent stem cells. NSCs and spontaneously differentiated non-neural cells were mixed and flowed through the spiral-shaped devices. Samples collected at the outlets were analyzed for purity and recovery. It was found that the device focused the NSCs into a narrow trajectory, which could then be collected in two out of the eight outlets. The device was tested at different flow rates and found that the most highly enriched fractions (2.1×) with NSCs recovery 93% were achieved at the flow rate (3 ml/min). Next, we extended our investigation from 2-loop design to 10-loop design to eliminate the use of sheath flow. NSCs were enriched to 2.5×, but only 38% of the NSCs were recovered from the most enriched fractions. Spiral-shaped microfluidic devices are capable of rapid, label-free enrichment of target stem cells, and have great potential in point-of-care tissue preparation.

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Acknowledgements

This research was sponsored by the US Army Medical Research and Materiel Command (USAMRMC) under SBIR contract No. W81XWH-12-C-0069 and W81XWH-15-C-0112. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the US Army. GJK and LMA acknowledge Dr. Alan Perantoni and Ms. Nirmala Sharma of the Cancer and Developmental Biology Laboratory providing access to specialized tissue culture facilities and for discussions regarding analysis of differentiation and development markers.

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Correspondence to Yi Wang.

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This article is part of the topical collection “2016 International Conference of Microfluidics, Nanofluidics and Lab-on-a-Chip, Dalian, China” guest edited by Chun Yang, Carolyn Ren and Xiangchun Xuan.

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Song, H., Rosano, J.M., Wang, Y. et al. Spiral-shaped inertial stem cell device for high-throughput enrichment of iPSC-derived neural stem cells. Microfluid Nanofluid 21, 64 (2017). https://doi.org/10.1007/s10404-017-1896-5

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Keywords

  • Induced pluripotent stem cells
  • Neural stem cell
  • Inertial microfluidic
  • Enrichment
  • Purification