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Abstract Cell culture encompasses procedures for extracting cells from their natural tissue and cultivating them under controlled artificial conditions. During this process, various factors, including cell physiological/morphological properties, culture environments, metabolites, and contaminants, have to be precisely controlled and monitored for the survival of cells and the pursuit of the desired properties of the cells. This review summarizes recent advances in sensor technologies and manufacturing strategies for various cell culture platforms using traditional plastics, microfluidic chips, and scalable bioreactors. We share the details of newly developed biological sensors, chemical sensors, optical sensors, electronic chip technologies, and material integration methods. The precise control of parameters based on the feedback by these sensors and electronics enhances cell culture quality and throughput.
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Single‐Use, Metabolite Absorbing, Resonant Transducer (SMART) Culture Vessels for Label‐Free, Continuous Cell Culture Progression Monitoring
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, andE. colicells 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.
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- Award ID(s):
- 2042503
- PAR ID:
- 10516201
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Science
- Volume:
- 11
- Issue:
- 32
- ISSN:
- 2198-3844
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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