extracellular matrix (ECM) and are lined by human intestinal epithelial (Caco-2)
mimicking the physiology of human intestine. To create, the gut microenvironment
the fluid is flown at a lower rate (30μLh^1 ) that results in low shear stress
(0.02 dyne cm^2 ) over the microchannels. These conditions lead to the change in
columnar epithelium that polarizes rapidly and spontaneously into folds resulting in
the recapitulation of the structure of intestinal villi and the formation of high
integrity barrier to small molecules that mimics whole intestine than cells in
cultured static Transwell models [ 36 ]. A cyclic suction controlled by a computer
vacuum manifold was used on both sides of the microchannels that repeatedly
stretch and relax the elastic ECM-coated porous membrane. The created rhythmic
mechanical deformations of the epithelial cell monolayer are similar to those
caused by peristaltic motions of the human intestine, (Fig.8.5C). Under this
condition, the phase contrast microscopic analysis of cell shape in human intestinal
epithelial monolayers increased linearly (0–30 %) for both substrate distortion and
cell deformation when the level of suction pressure was raised from 0 to 45 kPa.
Thus, the GoC microdevice provides a micro controlled- platform to study and
perturb critical gut functions in the presence of relevant physiological cues, includ-
ing cyclic mechanical strain, fluid flow, and coexistence of microbial flora.
An attempt has also been made to constitute a four organ chip system for
studying the homeostasis between the organs recapitulated [ 37 ]. The authors tried
to reconstruct kidney, liver, small intestine and skin equivalents on a multi-organ
chip and conducted studies related to barrier integrity, continuous molecular trans-
port against gradients and metabolic activity [ 28 ]. Researchers have even micro-
fabricated‘Body-on-a-Chip’devices that contain multiple micro-chambers each
containing cultured cells of different origin (e.g., liver epithelium vs. brain neurons)
that is connected to a network of micro-channels which permit the recirculation and
exchange in a physiologically relevant manner [ 38 , 39 ].
The technologies promise to have the potential to be more relevant functional
models for testing toxicity and efficacy, and allow a better insight into metabolic
activities at the tissue and organ levels. The several organ on chip devices, their
fabrication and operation parameters as well as applications have been summarized
in Tables8.1and8.2.
2.5 Single Cell Analysis
Considerable biochemical heterogeneity exists among cells of the same type caused
by many mechanisms including damage, mutations, stages in the cell cycle, and
differential exposure to external stimuli [ 50 ]. To better understand how and why
these differences arise is crucial in cell biology and early detection of disease
conditions. Many fascinating examples have been reported in the literature showing
the cell-cell variability and its significance to biological phenomena. For example,
the transcription events in mammalian cells are affected by random fluctuations,
leading to significant variations in mRNA copy numbers. In a clonal population of
204 S. Solanki and C.M. Pandey