This invention is aimed at controlling the pressure in 3D cell cultures. It consists of a combination of microfluidic channels, which surround the extracellular matrix (ECM), tunable pressure-regulated valves, which activate when a threshold pressure is reached in the ECM, and a repository, to direct excess gel away from the cell culture if the threshold pressure is exceeded. It can prevent leakage of gel between adjacent cell cultures in high-throughput arrays and is compatible with various cell culture materials and injection equipment.
Cell cultures are methods of extracting cells from an organism and fostering their proliferation in a suitable, non-native environment. They are especially useful to the both detection of microbes and the modeling of cellular biological phenomena such as tissue growth, both typical and atypical. In particular, 3D cell culture techniques are gaining traction over 2D techniques for their superior ability to mimic in vivo microenvironments.
In 3D cell cultures, the target cells are embedded in a three dimensional hydrogel, which acts as an artificial extracellular matrix (ECM) and fluid, containing nutrients, is often provided through microfluidic channels placed on either side of the ECM. As cell cultures are often batch-processed, it is important to keep the ECM hydrogel material from one cell culture from leaking into and blocking the channel supplying neighboring cell cultures. This can be especially challenging, as the nutrient delivery process may result in increased pressure and/or bubble formation in the ECM. There is a need for a pressure-regulated, automated technology for controlling fluid delivery into the ECM of 3D cell cultures that is compatible with different hydrogel materials and cell types, robust to gel leakage, and simple to use in high-throughput arrays.
Researchers at UCI have created a microfluidic device, which contains pressure-regulated valves capable of being customized to meet the pressure demands of each cell culture. As fluid is passed through the microfluidic channels into the gel ECM, if the pressure exceeds the pressure needed to burst the gel, the pressure valves will be activated and excess gel will be directed to an attached repository, instead of leaking into an adjacent cell culture. The system can be run automatically, or can be controlled manually, and it is also compatible with different types of fluid injection equipment (micropipettes, syringe pumps).
3D cell culture, microfluidics
Versatile, compatible with many different hydrogel and cell types, customizable pressure regulators, automated gel loading possible
A device has been tested and validated on a 3D cell culture using both manual and automated injection.
3D Cell Culture, Microfluidic Pressure Valve, Perfusion Cell Culture