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

Brian J. Archer, Julia J. Mack, Sara Acosta, Russell Nakasone, Fadi Dahoud, Khalid Youssef, Abraham Goldstein, Amichai Goldsman, Mathias C. Held, Martin Wiese, Bernhard Blumich, Matthias Wessling, Meike Emondts, Jurgen Klankermayer, M. Luisa Iruela-Arispe, Louis S. Bouchard

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2940-2947
Number of pages8
JournalIEEE Transactions on Biomedical Engineering
Volume68
Issue number10
DOIs
StatePublished - Oct 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 1964-2012 IEEE.

Funding

FundersFunder number
National Heart, Lung, and Blood InstituteT32HL069766

    Keywords

    • Biomanufacturing
    • MRI
    • bioreactor
    • cell density
    • hydrogel
    • noninvasive
    • proliferation
    • viability

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