TY - JOUR
T1 - Every breath you take
T2 - Non-invasive real-time oxygen biosensing in two- and three-dimensional microfluidic cell models
AU - Zirath, Helene
AU - Rothbauer, Mario
AU - Spitz, Sarah
AU - Bachmann, Barbara
AU - Jordan, Christian
AU - Müller, Bernhard
AU - Ehgartner, Josef
AU - Priglinger, Eleni
AU - Mühleder, Severin
AU - Redl, Heinz
AU - Holnthoner, Wolfgang
AU - Harasek, Michael
AU - Mayr, Torsten
AU - Ertl, Peter
PY - 2018/7/3
Y1 - 2018/7/3
N2 - Knowledge on the availability of dissolved oxygen inside microfluidic cell culture systems is vital for recreating physiological-relevant microenvironments and for providing reliable and reproducible measurement conditions. It is important to highlight that in vivo cells experience a diverse range of oxygen tensions depending on the resident tissue type, which can also be recreated in vitro using specialized cell culture instruments that regulate external oxygen concentrations. While cell-culture conditions can be readily adjusted using state-of-the-art incubators, the control of physiological-relevant microenvironments within the microfluidic chip, however, requires the integration of oxygen sensors. Although several sensing approaches have been reported to monitor oxygen levels in the presence of cell monolayers, oxygen demands of microfluidic three-dimensional (3D)-cell cultures and spatio-temporal variations of oxygen concentrations inside two-dimensional (2D) and 3D cell culture systems are still largely unknown. To gain a better understanding on available oxygen levels inside organ-on-a-chip systems, we have therefore developed two different microfluidic devices containing embedded sensor arrays to monitor local oxygen levels to investigate (i) oxygen consumption rates of 2D and 3D hydrogel-based cell cultures, (ii) the establishment of oxygen gradients within cell culture chambers, and (iii) influence of microfluidic material (e.g., gas tight vs. gas permeable), surface coatings, cell densities, and medium flow rate on the respiratory activities of four different cell types. We demonstrate how dynamic control of cyclic normoxic-hypoxic cell microenvironments can be readily accomplished using programmable flow profiles employing both gas-impermeable and gas-permeable microfluidic biochips.
AB - Knowledge on the availability of dissolved oxygen inside microfluidic cell culture systems is vital for recreating physiological-relevant microenvironments and for providing reliable and reproducible measurement conditions. It is important to highlight that in vivo cells experience a diverse range of oxygen tensions depending on the resident tissue type, which can also be recreated in vitro using specialized cell culture instruments that regulate external oxygen concentrations. While cell-culture conditions can be readily adjusted using state-of-the-art incubators, the control of physiological-relevant microenvironments within the microfluidic chip, however, requires the integration of oxygen sensors. Although several sensing approaches have been reported to monitor oxygen levels in the presence of cell monolayers, oxygen demands of microfluidic three-dimensional (3D)-cell cultures and spatio-temporal variations of oxygen concentrations inside two-dimensional (2D) and 3D cell culture systems are still largely unknown. To gain a better understanding on available oxygen levels inside organ-on-a-chip systems, we have therefore developed two different microfluidic devices containing embedded sensor arrays to monitor local oxygen levels to investigate (i) oxygen consumption rates of 2D and 3D hydrogel-based cell cultures, (ii) the establishment of oxygen gradients within cell culture chambers, and (iii) influence of microfluidic material (e.g., gas tight vs. gas permeable), surface coatings, cell densities, and medium flow rate on the respiratory activities of four different cell types. We demonstrate how dynamic control of cyclic normoxic-hypoxic cell microenvironments can be readily accomplished using programmable flow profiles employing both gas-impermeable and gas-permeable microfluidic biochips.
KW - 3D culture
KW - Biosensor
KW - Hydrogel
KW - Lab-on-a-chip
KW - Microfluidics
KW - Organ-on-a-chip
KW - Oxygen
KW - Oxygen gradient
UR - http://www.scopus.com/inward/record.url?scp=85049848781&partnerID=8YFLogxK
U2 - 10.3389/fphys.2018.00815
DO - 10.3389/fphys.2018.00815
M3 - Article
AN - SCOPUS:85049848781
VL - 9
JO - Frontiers in Physiology
JF - Frontiers in Physiology
IS - JUL
M1 - 815
ER -