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A quartz crystal resonator for cellular phenotyping

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journal contribution
posted on 29.10.2020, 10:04 by Carlos Da-Silva-Granja, Katie GlenKatie Glen, Niklas Sandström, Victor P Ostanin, Rob ThomasRob Thomas, Sourav GhoshSourav Ghosh
Cell therapy manufacturing is limited by lack of online tools capable of realtime in-process monitoring, particularly of simultaneous changes in multiple orthogonal (mutually independent) parameters. Here, we studied changes in CD36 expression, number density and size (area) of erythroblasts through different stages of erythropoiesis in vitro using a quartz crystal resonator (QCR), integrated with a microscope, and flow cytometry in parallel. An analytical model was developed extending the Kanazawa-Gordon theory. Based on this model, independent correlations were established between changes in each QCR parameter, dissipation (∆Γ) and resonance frequency (〖-Δf〗_0), and CD36 expression (from flow cytometry) and cell area (from microscope). The correlation functions were used to derive an acoustic signature (-∆Γ/〖Δf〗_0) of the differentiation process that uniquely mapped the relative changes in CD36 expression and late-stage enucleation-related deviations. A method to quantify relative changes in cell area purely from the acoustic parameters was also proposed. This work demonstrated for the first time the potential of an electromechanical tool for online monitoring of concurrently varying orthogonal phenotypic parameters in cell therapy manufacturing.

Funding

Tackling Antimicrobial Resistance: An Interdisciplinary Approach

Engineering and Physical Sciences Research Council

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Engineering Biological Science - Processes and Systems for Haematopoietic Stem Cell Based Therapy Manufacture

Engineering and Physical Sciences Research Council

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History

School

  • Mechanical, Electrical and Manufacturing Engineering

Published in

Biosensors and Bioelectronics: X

Volume

6

Publisher

Elsevier BV

Version

VoR (Version of Record)

Rights holder

© The Authors

Publisher statement

This is an Open Access Article. It is published by Elsevier under the Creative Commons Attribution 4.0 International Licence (CC BY 4.0). Full details of this licence are available at: https://creativecommons.org/licenses/by/4.0/

Acceptance date

12/10/2020

Publication date

2020-10-17

Copyright date

2020

ISSN

2590-1370

Language

en

Depositor

Mr Carlos Da Silva Granja. Deposit date: 27 October 2020

Article number

100057