membrane that is exerted by airflow and fluidic flow respectively via the two
channels separated by the membrane. The mechanical forces are operated by two
channels beside the main channel. Though complex geometries have been applied
to MF system, the models are still small and simple. This device provides a
comprehensive tool for lung disease research and related drug screening.
Recently brain on a chip has been reconstructed on MF chip using co-cultured
endothelial cells and astrocytes by combining the fluidic shear stress and thin
membrane (Fig. 8.5A). This fabricated blood–brain barrier (μBBB) model
addresses the previous limitations of fluidic shear stress (static transwell models)
and thin dual cell layer interface (conventional dynamic in vitro BBB model). The
results indicate that this proposed model might be a valid prototype for simulating
the function ofμBBB. The fabricated multi-layered microfluidicμBBB device
consists of four PDMS substrates, two glass layers, and in the center between the
PDMS layers there is a porous polycarbonate membrane (Fig.8.5A). To ensure the
laminar flow the height of the channel is 200μm, and the width at the cell culture
interface is 2 mm (luminal) or 5 mm (abluminal). The porous membrane located at
the channel junction has an area of 10 mm^2. To introduce dynamic flow the
assembled device houses two perpendicularly crossing channels with a porous
membrane at the intersection of the flow channels for cell culture, and to monitor
trans-endothelial electrical resistance (TEER) multiple embedded electrodes are
introduced across the barrier. Opposite to the membrane on each side are two sets of
two AgCl thin-film TEER electrode pairs forming a four-point sensing structure.
The fabricatedμBBB platform was sterilized and adhesion seeded by steadily
perfusing for up to 7 days. The developedμBBB successfully mimicked the
dynamic cerebrovascular environment with fluid shear stress. Further, thisμBBB
model can be effectively used to monitor the changes in the barrier function such as
barrier-enhancing or barrier opening drugs [ 31 , 32 ].
Researchers have also fabricated an MF cell culture device mimicking the
microscopic structure in liver tissue (hepatic cords) (Fig.8.5B). The MF device
consists of a medium flow channel with a width of 100μm and a height of 30μm,
with a cell loading channel (200μm width and 30μm height), a cell culture area
(37μm width and 30μm height), and an endothelial-like barrier [ 35 ]. For the
smooth alignment of the hepatocytes in two lines, the tip of the cell culture area was
asymmetrical design with a width of 37μm which can accommodate two cells side-
by-side. To avoid the deformation of the cells the cross-sectional area of the slits
was minimize, (2μm wide and 2μm high). For efficient simulation of the flow in
the device COMSOL MULTIPHYSICS COMSOL, Inc. was used (Fig.8.5B). The
obtained simulation results show that the flow velocity in the medium flow channel
is 1 mm s^1 , which is nearly same as the velocity of blood flow in vivo. Under
perfusion condition, the flow velocity in the cell culture area is 0 mm/s whereas the
flow rate determined is 0.1μL min^1. To further, avoid the greater fluidic resistance
of the endothelial-like barrier in comparison to the medium flow channel both the
cell inlet and cell outlet were sealed [ 33 ].
A recent human gut-on-a-chip (GoC) model tried to build a more physiologically
relevant in vitro model of the human intestine that undergoes peristalsis,
202 S. Solanki and C.M. Pandey