Microfluidic device to attain high spatial and temporal control of oxygen

Area of Science:

• Biotechnology and Biomedical Engineering
• Cell Biology and Physiology
• Vascular Biology and Angiogenesis

Background:

• Microfluidic devices are valuable for recreating in vitro biological microenvironments.
• A key limitation is the inability to replicate physiological oxygen levels (typically ~5% O2) compared to atmospheric levels (21% O2).
• Oxygen gradients are critical for understanding in vivo biological processes and disease states.

Purpose of the Study:

• To develop a microfluidic device capable of controlling spatial and temporal oxygen variations.
• To validate the biological relevance of the device using a 3D sprouting angiogenesis assay.
• To investigate the effects of hypoxia on vascular network formation.

Main Methods:

• A microfluidic device with three parallel tissue chambers and an adjacent oxygen scavenger channel was designed.
• Oxygen levels were mapped using phosphorescent lifetime imaging microscopy and validated with computational modeling.
• A 3D sprouting angiogenesis assay involved co-culturing endothelial and fibroblast cells, followed by induction of oxygen gradients using sodium sulfite.

Main Results:

• The microfluidic device successfully created controlled spatial and temporal oxygen gradients.
• Both constant chronic and intermittent hypoxia were shown to bias vessel growth.
• Constant chronic hypoxia induced a greater degree of biased angiogenesis compared to intermittent hypoxia.

Conclusions:

• The developed microfluidic platform offers precise control over oxygen gradients in engineered tissues.
• This system can be used to study oxygen-dependent biological processes, including angiogenesis under hypoxic conditions.
• The platform has potential applications in modeling diseases like cancer and ischemic heart disease.