Transport and shear in a microfluidic membrane bilayer device for cell culture

Abstract

Microfluidic devices have been established as useful platforms for cell culture for a broad range of applications, but challenges associated with controlling gradients of oxygen and other soluble factors and hemodynamic shear forces in small, confined channels have emerged. For instance, simple microfluidic constructs comprising a single cell culture compartment in a dynamic flow condition must handle tradeoffs between sustaining oxygen delivery and limiting hemodynamic shear forces imparted to the cells. These tradeoffs present significant difficulties in the culture of mesenchymal stem cells ͑MSCs͒, where shear is known to regulate signaling, proliferation, and expression. Several approaches designed to shield cells in microfluidic devices from excessive shear while maintaining sufficient oxygen concentrations and transport have been reported. Here we present the relationship between oxygen transport and shear in a "membrane bilayer" microfluidic device, in which soluble factors are delivered to a cell population by means of flow through a proximate channel separated from the culture channel by a membrane. We present an analytical model that describes the characteristics of this device and its ability to independently modulate oxygen delivery and hemodynamic shear imparted to the cultured cells. This bilayer configuration provides a more uniform oxygen concentration profile that is possible in a single-channel system, and it enables independent tuning of oxygen transport and shear parameters to meet requirements for MSCs and other cells known to be sensitive to hemodynamic shear stresses.

Bioreactor technologies to support liver function in vitro

“…Primary hepatocytes increased their per-cell rate of albumin secretion over a week of culture in the device, and secreted albumin at higher rates than in control static cultures [75]. Subsequent diffusion-reaction modeling of oxygen transport and consumption in this device suggests that oxygen may become limited at high cell densities [88], however experimental verification of oxygen gradients would shed more light on the apparent high viability of dense hepatocyte monolayers. To our knowledge, these devices have not been commercialized.…”

Membrane-integrated microfluidic device for high-resolution live cell imaging

“…However, in previous work, 4 viable cell culture has been sustained in a similar membrane-integrated dual cell chamber system for weeks supporting the viability hypothesis of our device. In addition, the effective membrane permeability has been modeled for dual chamber device 20 in a similar configuration and a similar membrane. The model predicted sufficient oxygen concentrations for cells in the lower chamber, suggesting sufficient oxygen gas transfer in this device.…”

Integrated hiPSC-based liver and heart microphysiological systems predict unsafe drug-drug interaction

“…Small flows within cell culture chambers in membrane bilayer microfluidic devices have been considered elsewhere 88,89 .…”