Every Breath You Take: Non-invasive Real-Time Oxygen Biosensing in Two- and Three-Dimensional Microfluidic Cell Models

Abstract

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.

Fabrication and Functionalization of 3D Printed Polydimethylsiloxane‐Based Microfluidic Devices Obtained through Digital Light Processing

“…[ 42 ] Moreover, a truly 3D microchannel architecture was obtained, which can be exploited for different applications such as for the manufacturing of complex and passive microfluidic mixer with various 3D configurations [ 55 ] or the fabrication of a 3D lab‐on‐a‐chip for cell culture and biological analysis. [ 56 ]…”

A compression transmission device for the evaluation of bonding strength of biocompatible microfluidic and biochip materials and systems

“…To investigate the bonding strength of advanced microfluidic and biochip structures two established and published systems were used. To evaluate the bonding strength of cell-based microfluidic device composed of glass and biocompatible pressure sensitive adhesive tapes (ARseal 90880 and ARcare 8259) the design and fabrication used as previousl 29 . The single channel system was manufactured with in base dimensions of 20 × 15 mm to be mounted within the device.…”

“…After evaluating the bonding strength between different combinations of biocompatible materials,entire advanced cell-based microfluidic and biochip systems are tested. To investigate non-invasive real-time oxygen biosensing in two-and three-dimensional microfluidic cell models a bio chip composed out of glass and biocompatible pressure sensitive adhesive tapes was developed29 . The single microfluidic system within the dimensions of 20 × 15 mm was rebuilt for the bonding testing device, mounted and tested (seeFig.…”

Cultivation and characterization of human midbrain organoids in sensor integrated microfluidic chips

“…After drying for 2 h at room temperature, the microparticles were immobilized to the glass substrate and the fluidic structures were sealed, employing air plasma. 9 Prior to use microfluidic devices were sterilized employing 70 % ethanol as well as UV plasma.…”