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Author Notes:

Corresponding authors: S. Nie, snie@emory.edu; C. Xu, chunhui.xu@emory.edu.

We thank Dr. Joshua T. Maxwell for kindly providing the primary rat cardiomyocytes and Ms. Marcela Preininger for carefully reviewing and editing the manuscript. We thank the Children's Healthcare of Atlanta and Emory University Pediatric Flow Cytometry Core and Animal Physiology Core.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Images from Servier Medical Art were used in Fig. 1A.

The authors indicated no potential conflicts of interest.


Research Funding:

This project was supported in part by the Center for Pediatric Nanomedicine at the Emory • Children’s • GT Pediatric Research Alliance, the NIH grant R21HL123928 to C.X, a grant No. 51373024 to Z. Y. from the National Natural Science Foundation of China, and a seed grant to C.X. from the National Center for Advancing Translational Sciences of the NIH under Award Number UL1TR000454.


  • Differentiation
  • Flow cytometry
  • Human pluripotent stem cell
  • Nanoparticle
  • SERS assay

Novel surface-enhanced Raman scattering-based assays for ultra-sensitive detection of human pluripotent stem cells


Journal Title:



Volume 105


, Pages 66-76

Type of Work:

Article | Final Publisher PDF


Human pluripotent stem cells (hPSCs) are a promising cell source for regenerative medicine, but their derivatives need to be rigorously evaluated for residual stem cells to prevent teratoma formation. Here, we report the development of novel surface-enhanced Raman scattering (SERS)-based assays that can detect trace numbers of undifferentiated hPSCs in mixed cell populations in a highly specific, ultra-sensitive, and time-efficient manner. By targeting stem cell surface markers SSEA-5 and TRA-1-60 individually or simultaneously, these SERS assays were able to identify as few as 1 stem cell in 106 cells, a sensitivity (0.0001%) which was ∼2000 to 15,000-fold higher than that of flow cytometry assays. Using the SERS assay, we demonstrate that the aggregation of hPSC-based cardiomyocyte differentiation cultures into 3D spheres significantly reduced SSEA-5+ and TRA-1-60+ cells compared with parallel 2D cultures. Thus, SERS may provide a powerful new technology for quality control of hPSC-derived products for preclinical and clinical applications.

Copyright information:

© 2016 The Authors.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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