Skip to main content
SpringerLink
Log in

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

  • Research Paper
  • Published:
Microfluidics and Nanofluidics Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • Bhagat AAS, Kuntaegowdanahalli SS, Papautsky I (2008) Continuous particle separation in spiral microchannels using dean flows and differential migration. Lab Chip 8(11):1906–1914

    Article  Google Scholar 

  • Bhagat AAS et al (2011) Pinched flow coupled shear-modulated inertial microfluidics for high-throughput rare blood cell separation. Lab Chip 11(11):1870–1878

    Article  Google Scholar 

  • Burridge PW et al (2014) Chemically defined generation of human cardiomyocytes. Nat Methods 11(8):855–860

    Article  Google Scholar 

  • Davis JA et al (2006) Deterministic hydrodynamics: taking blood apart. Proc Natl Acad Sci 103(40):14779–14784

    Article  Google Scholar 

  • Di Carlo D (2009) Inertial microfluidics. Lab Chip 9(21):3038–3046

    Article  Google Scholar 

  • Di Carlo D et al (2007) Continuous inertial focusing, ordering, and separation of particles in microchannels. Proc Natl Acad Sci 104(48):18892–18897

    Article  Google Scholar 

  • Geng Z et al (2013) Continuous blood separation utilizing spiral filtration microchannel with gradually varied width and micro-pillar array. Sens Actuators B Chem 180:122–129

    Article  Google Scholar 

  • Ghaedi M et al (2013) Human iPS cell–derived alveolar epithelium repopulates lung extracellular matrix. J Clin Investig 123(11):4950

    Article  Google Scholar 

  • Gossett DR et al (2010) Label-free cell separation and sorting in microfluidic systems. Anal Bioanal Chem 397(8):3249–3267

    Article  Google Scholar 

  • Gregoratto I, McNeil CJ, Reeks MW (2007) Micro-devices for rapid continuous separation of suspensions for use in micro-total-analysis-systems (μTAS). In: MOEMS-MEMS 2007 Micro and Nanofabrication. International Society for Optics and Photonics

  • Hou HW et al (2013) Isolation and retrieval of circulating tumor cells using centrifugal forces. Sci Rep 3:1259

    Google Scholar 

  • Hu B-Y et al (2010) Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. Proc Natl Acad Sci 107(9):4335–4340

    Article  Google Scholar 

  • Huang LR et al (2004) Continuous particle separation through deterministic lateral displacement. Science 304(5673):987–990

    Article  Google Scholar 

  • Hur SC et al (2011) Deformability-based cell classification and enrichment using inertial microfluidics. Lab Chip 11(5):912–920

    Article  Google Scholar 

  • Hur SC et al (2012) Label-free enrichment of adrenal cortical progenitor cells using inertial microfluidics. PLoS One 7(10):46550

    Article  Google Scholar 

  • Inglis DW et al (2006) Critical particle size for fractionation by deterministic lateral displacement. Lab Chip 6(5):655–658

    Article  Google Scholar 

  • Jeon K et al (2012) Differentiation and transplantation of functional pancreatic beta cells generated from induced pluripotent stem cells derived from a type 1 diabetes mouse model. St Cells Dev 21(14):2642–2655

    Article  Google Scholar 

  • Johnston I et al (2014) Dean flow focusing and separation of small microspheres within a narrow size range. Microfluid Nanofluidics 17(3):509–518

    Article  Google Scholar 

  • Kim YW, Yoo JY (2008) The lateral migration of neutrally-buoyant spheres transported through square microchannels. J Micromec Microeng 18(6):065015

    Article  Google Scholar 

  • Kuntaegowdanahalli SS et al (2009) Inertial microfluidics for continuous particle separation in spiral microchannels. Lab Chip 9(20):2973–2980

    Article  Google Scholar 

  • Lee WC et al (2011) High-throughput cell cycle synchronization using inertial forces in spiral microchannels. Lab Chip 11(7):1359–1367

    Article  Google Scholar 

  • Lian Q et al (2010) Future perspective of induced pluripotent stem cells for diagnosis, drug screening and treatment of human diseases. Thromb Haemost 104(1):39

    Article  Google Scholar 

  • Liu Z et al (2013) Rapid isolation of cancer cells using microfluidic deterministic lateral displacement structure. Biomicrofluidics 7(1):011801

    Article  Google Scholar 

  • Martel JM, Toner M (2012) Inertial focusing dynamics in spiral microchannels. Phys Fluids 24(3):032001 (1994-present)

    Article  Google Scholar 

  • Nivedita N, Papautsky I (2013) Continuous separation of blood cells in spiral microfluidic devices. Biomicrofluidics 7(5):054101

    Article  Google Scholar 

  • Risbud SR, Drazer G (2014) Mechanism governing separation in microfluidic pinched flow fractionation devices. Microfluid Nanofluidics 17(6):1003–1009

    Article  Google Scholar 

  • Srivastav A, Podgorski T, Coupier G (2012) Efficiency of size-dependent particle separation by pinched flow fractionation. Microfluid Nanofluidics 13(5):697–701

    Article  Google Scholar 

  • Sun J et al (2012) Double spiral microchannel for label-free tumor cell separation and enrichment. Lab Chip 12(20):3952–3960

    Article  Google Scholar 

  • Sun J et al (2013) Size-based hydrodynamic rare tumor cell separation in curved microfluidic channels. Biomicrofluidics 7(1):011802

    Article  Google Scholar 

  • Svendsen CN (2013) Back to the future: how human induced pluripotent stem cells will transform regenerative medicine. Hum Mol Genet 22(R1):R32–R38

    Article  Google Scholar 

  • Warkiani ME et al (2014) Slanted spiral microfluidics for the ultra-fast, label-free isolation of circulating tumor cells. Lab Chip 14(1):128–137

    Article  Google Scholar 

  • Yamada M, Nakashima M, Seki M (2004) Pinched flow fractionation: continuous size separation of particles utilizing a laminar flow profile in a pinched microchannel. Anal Chem 76(18):5465–5471

    Article  Google Scholar 

  • Zhang B et al (2012) Label-free enrichment of functional cardiomyocytes using microfluidic deterministic lateral flow displacement. PLoS ONE 7(5):e37619

    Article  Google Scholar 

  • Zhang J et al (2014) Particle inertial focusing and its mechanism in a serpentine microchannel. Microfluid Nanofluidics 17(2):305–316

    Article  MathSciNet  Google Scholar 

  • Zuvin M et al (2016) Human breast cancer cell enrichment by Dean flow driven microfluidic channels. Microsyst Technol 22(3):645–652

    Article  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. CFD Research Corporation, 701 McMillian Way NW, Huntsville, AL, 35806, USA

    Hongjun Song, Jenna M. Rosano, Yi Wang, Charles J. Garson, Balabhaskar Prabhakarpandian & Kapil Pant

  2. Cancer and Developmental Biology Laboratory, National Cancer Institute, Frederick, MD, 21702, USA

    George J. Klarmann & Luis M. Alvarez

  3. Department of Chemistry and Life Sciences, United States Military Academy, West Point, NY, 10996, USA

    Luis M. Alvarez

  4. Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD, 21218, USA

    Eva Lai

  5. Telemedicine and Advanced Technology Research Center (TATRC), U.S. Army Medical Research and Materiel Command (USAMRMC), 1054 Patchel Street, Fort Detrick, MD, 21702, USA

    Eva Lai

Authors
  1. Hongjun Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jenna M. Rosano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Charles J. Garson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Balabhaskar Prabhakarpandian
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kapil Pant
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. George J. Klarmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Luis M. Alvarez
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Eva Lai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yi Wang.

Additional information

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10404-017-1896-5

Keywords

Search

Navigation