Single-Use, Metabolite Absorbing, Resonant Transducer (SMART) Culture Vessels for Label-Free, Continuous Cell Culture Progression Monitoring.

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  • Additional Information
    • Source:
      Publisher: WILEY-VCH Country of Publication: Germany NLM ID: 101664569 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2198-3844 (Electronic) Linking ISSN: 21983844 NLM ISO Abbreviation: Adv Sci (Weinh) Subsets: MEDLINE
    • Publication Information:
      Original Publication: Weinheim : WILEY-VCH, [2014]-
    • Subject Terms:
      Cell Culture Techniques*/methods ; Cell Culture Techniques*/instrumentation ; Cricetulus* ; Transducers*; Humans ; Animals ; CHO Cells ; HeLa Cells ; Cricetinae ; HEK293 Cells ; Equipment Design/methods ; Escherichia coli/metabolism ; Cell Proliferation/physiology
    • Abstract:
      Secreted metabolites are an important class of bio-process analytical technology (PAT) targets that can correlate to cell conditions. However, current strategies for measuring metabolites are limited to discrete measurements, resulting in limited understanding and ability for feedback control strategies. Herein, a continuous metabolite monitoring strategy is demonstrated using a single-use metabolite absorbing resonant transducer (SMART) to correlate with cell growth. Polyacrylate is shown to absorb secreted metabolites from living cells containing hydroxyl and alkenyl groups such as terpenoids, that act as a plasticizer. Upon softening, the polyacrylate irreversibly conformed into engineered voids above a resonant sensor, changing the local permittivity which is interrogated, contact-free, with a vector network analyzer. Compared to sensing using the intrinsic permittivity of cells, the SMART approach yields a 20-fold improvement in sensitivity. Tracking growth of many cell types such as Chinese hamster ovary, HEK293, K562, HeLa, and E. coli cells as well as perturbations in cell proliferation during drug screening assays are demonstrated. The sensor is benchmarked to show continuous measurement over six days, ability to track different growth conditions, selectivity to transducing active cell growth metabolites against other components found in the media, and feasibility to scale out for high throughput campaigns.
      (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
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    • Grant Information:
      2042503 National Science Foundation
    • Contributed Indexing:
      Keywords: continuous cell growth monitoring; inductive‐capacitive sensor; non‐destructive metabolite sensing; polyacrylate; process analytical technology
    • Publication Date:
      Date Created: 20240620 Date Completed: 20240827 Latest Revision: 20240829
    • Publication Date:
      20240830
    • Accession Number:
      PMC11348071
    • Accession Number:
      10.1002/advs.202401260
    • Accession Number:
      38900081