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Biosens Bioelectron. 2019 Jan 1;123:131-140. doi: 10.1016/j.bios.2018.07.035. Epub 2018 Jul 21.

Integrated phosphorescence-based photonic biosensor (iPOB) for monitoring oxygen levels in 3D cell culture systems.

Author information

1
Joint Department of Biomedical Engineering, North Carolina State University and University of North Carolina at Chapel Hill, 911 Oval Dr., Raleigh, NC 27695, USA.
2
Department of Electrical & Computer Engineering, North Carolina State University, 890 Oval Dr., Raleigh, NC 27695, USA.
3
Profusa, Inc., 345 Allerton Ave., South San Francisco, CA 94080, USA.
4
Joint Department of Biomedical Engineering, North Carolina State University and University of North Carolina at Chapel Hill, 911 Oval Dr., Raleigh, NC 27695, USA; Department of Cell Biology & Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
5
Joint Department of Biomedical Engineering, North Carolina State University and University of North Carolina at Chapel Hill, 911 Oval Dr., Raleigh, NC 27695, USA; Department of Electrical & Computer Engineering, North Carolina State University, 890 Oval Dr., Raleigh, NC 27695, USA. Electronic address: mdaniel6@ncsu.edu.

Abstract

Physiological processes, such as respiration, circulation, digestion, and many pathologies alter oxygen concentration in the blood and tissue. When designing culture systems to recapitulate the in vivo oxygen environment, it is important to integrate systems for monitoring and controlling oxygen concentration. Herein, we report the design and engineering of a system to remotely monitor and control oxygen concentration inside a device for 3D cell culture. We integrate a photonic oxygen biosensor into the 3D tissue scaffold and regulate oxygen concentration via the control of purging gas flow. The integrated phosphorescence-based oxygen biosensor employs the quenching of palladium-benzoporphyrin by molecular oxygen to transduce the local oxygen concentration in the 3D tissue scaffold. The system is validated by testing the effects of normoxic and hypoxic culture conditions on healthy and tumorigenic breast epithelial cells, MCF-10A cells and BT474 cells, respectively. Under hypoxic conditions, both cell types exhibited upregulation of downstream target genes for the hypoxia marker gene, hypoxia-inducible factor 1α (HIF1A). Lastly, by monitoring the real-time fluctuation of oxygen concentration, we illustrated the formation of hypoxic culture conditions due to limited diffusion of oxygen through 3D tissue scaffolds.

KEYWORDS:

Biosensors; Hypoxia; Microdevice; Organs-on-chips; Oxygen; Oxygen biosensor

PMID:
30060990
PMCID:
PMC6376985
DOI:
10.1016/j.bios.2018.07.035
[Indexed for MEDLINE]
Free PMC Article

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