Mapping Cell Viability Quantitatively and Independently From Cell Density in 3D Gels Noninvasively

IEEE Transactions on Biomedical Engineering, vol. 68, pp. 2940–2947

Abstract

Objective:In biomanufacturing there is a need for quantitative methods to map cell viability and density inside 3D bioreactors to assess health and proliferation over time. Recently, noninvasive MRI readouts of cell density have been achieved. However, the ratio of live to dead cells was not varied. Herein we present an approach for measuring the viability of cells embedded in a hydrogel independently from cell density to map cell number and health.Methods:Independent quantification of cell viability and density was achieved by calibrating the$\boldsymbol{^1}$H magnetization transfer- (MT) and diffusion-weighted NMR signals to samples of known cell density and viability using a multivariate approach. Maps of cell viability and density were generated by weighting NMR images by these parameters post-calibration.Results:Using this method, the limits of detection (LODs) of total cell density and viable cell density were found to be$\boldsymbol{3.88 \times 10^{8}}$cells$\boldsymbol{\cdot }$mL$\boldsymbol{^{-1}\cdot }$Hz$\boldsymbol{^{-1/2}}$and$\boldsymbol{2.36 \times 10^{9}}$viable cells$\boldsymbol{\cdot }$mL$\boldsymbol{^{-1}\cdot }$Hz$\boldsymbol{^{-1/2}}$respectively.Conclusion:This mapping technique provides a noninvasive means of visualizing cell viability and number density within optically opaque bioreactors.Significance:We anticipate that such nondestructive readouts will provide valuable feedback for monitoring and controlling cell populations in bioreactors.

Authors 14

1. Brian J. Archer

   University of California, Los Angeles

   Affiliation as printed

   Department of Bioengineering, University of California, Los Angeles, USA

2. Julia J. Mack

   University of California System

   Affiliation as printed

   Department of Medicine, Division of Cardiology, University of California, USA

3. Russell Nakasone

   University of California, Los Angeles

   Affiliation as printed

   Department of Chemistry and Biochemistry, University of California, Los Angeles, USA

4. Fadi Dahoud

   University of California, Los Angeles

   Affiliation as printed

   Department of Chemistry and Biochemistry, University of California, Los Angeles, USA

5. Khalid Youssef

   Cedars-Sinai Medical Center

   Affiliation as printed

   Cedars-Sinai Medical Center, USA

6. Amichai Goldsman

   University of California, Los Angeles

   Affiliation as printed

   Department of Chemistry and Biochemistry, University of California, Los Angeles, USA

7. Mathias Held Aachen Department of Chemical Engineering

   RWTH Aachen University

   Affiliation as printed

   Department of Chemical Engineering, Chemical Process Engineering, RWTH Aachen University, Germany

8. Martin Wiese Aachen Department of Chemical Engineering

   RWTH Aachen University

   Affiliation as printed

   Department of Chemical Engineering, Chemical Process Engineering, RWTH Aachen University, Germany

9. Bernhard Blümich Aachen Institute of Technical and Macromolecular Chemistry

   RWTH Aachen University

   Affiliation as printed

   Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Germany

10. Matthias Weßling Aachen Department of Chemical Engineering

    RWTH Aachen University

    Affiliation as printed

    Department of Chemical Engineering, Chemical Process Engineering, RWTH Aachen University, Germany

11. Meike Emondts Aachen Institute of Technical and Macromolecular Chemistry

    RWTH Aachen University

    Affiliation as printed

    Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Germany

12. Jürgen Klankermayer Aachen Institute of Technical and Macromolecular Chemistry

    RWTH Aachen University

    Affiliation as printed

    Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Germany

13. M. Luisa Iruela‐Arispe

    Northwestern University

    Affiliation as printed

    Department of Cell and Developmental Biology, Northwestern University, USA

14. Louis‐S. Bouchard

    University of California, Los Angeles

    Affiliation as printed

    Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA

    Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, USA