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A microfluidic platform for dissociating clinical scale tissue samples into single cells

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Abstract

The advancement of sample preparation techniques is essential for the field of cell-based therapeutics. To obtain cells suited for clinical applications, the entire process starting from acquiring donor tissue biopsy, all through cell transplantation into the recipient, should occur in an integrated, safe, and efficient system. The current laboratory approach for solid tissue-to-cell isolation is invasive and involves multiple incoherent manual procedures running in an open operator-dependent system. Such an approach provides a chain of events for systematic cell loss that would be unfavorable for rare cell populations such as adult and cancer stem cells. A few lab-on-chip platforms were proposed to process biological tissues, however, they were limited to partial tissue dissociation and required additional processing off-chip. Here, we report the first microfluidic platform that can dissociate native biological tissue into ready-to-use single cells. The platform can merge the successive steps of tissue dissociation, debris filtration, cell sieving, washing, and staining in one streamlined process. Performance of the platform was tested with diverse biological tissues and it could yield viable cells that were ready for on or off-chip cell culture without further processing. Microfluidic tissue dissociation using this platform produced a higher number of viable single cells (an average of 2262 cells/ml per milligram of tissue compared to 1233.25 cells/ml/mg with conventional dissociation).

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Data availability

All experimental data including data analysis, images, and videos are available on request with the corresponding author.

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Acknowledgments

We acknowledge the Center of Nanotechnology (CNT) at Zewail City of Science and Technology for utilizing the clean room during initial device fabrication and the American University in Cairo for using the scanning electron microscopy. We also acknowledge our several collaborating institutes at Sheikh Zayed Hospital, the Obstetrics Department and the Microfluidics Lab at Assiut University, and the Center of Excellence for Stem Cells and Regenerative Medicine at Zewail City for providing biological samples, the use of culture facilities, and labs in running study experiments.

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Authors and Affiliations

  1. Department of Chemistry, American University of Cairo, Cairo, Egypt

    Saif Al-Mofty

  2. Institute of Biomedical Engineering, University of Toronto, Toronto, Canada

    Mohamed Elsayed

  3. Mechanical Engineering Department, Assiut University, Asyut, Egypt

    Hassan Ali & Mohamed Abdelgawad

  4. Assiut University Hospitals, Faculty of Medicine, Assiut University, Asyut, Egypt

    Omnia Ahmed & Ahmed Wahby

  5. Future Industries Institute, University of South Australia, Adelaide, Australia

    Ahmad Altayyeb

  6. Department of Mechanical Engineering, American University of Sharjah, Sharjah, United Arab Emirates

    Mohamed Abdelgawad

  7. Department of Clinical Sciences, College of Medicine, University of Sharjah, M-27, P. O. Box 27272, Sharjah, United Arab Emirates

    Noha Mousa

Authors
  1. Saif Al-Mofty
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  2. Mohamed Elsayed
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  3. Hassan Ali
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  4. Omnia Ahmed
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  5. Ahmad Altayyeb
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  6. Ahmed Wahby
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  7. Mohamed Abdelgawad
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  8. Noha Mousa
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Contributions

SA wrote the first draft of manuscript and performed dissociation and culture experiments. ME contributed to the design of prototype 2 and fabrication of prototype 1. HA performed CAD and simulation work and contributed to design of prototypes 1 and 2. OA contributed to dissociation experiments as well as device fabrication. AA contributed to device fabrication of prototype 2 in the cleanroom. AW helped in testing the cell-trap. MA supervised device design and fabrication and contributed to manuscript writing and revision. NM conceived the idea of the platform, planned and supervised experiments, wrote the first draft and all revised versions of the manuscript.

Corresponding authors

Correspondence to Mohamed Abdelgawad or Noha Mousa.

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Al-Mofty, S., Elsayed, M., Ali, H. et al. A microfluidic platform for dissociating clinical scale tissue samples into single cells. Biomed Microdevices 23, 10 (2021). https://doi.org/10.1007/s10544-021-00544-5

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