Currently, culturing Caco-2 cells in a Gut-on-a-chip
(GOC) is well-accepted
for developing intestinal disease models and drug screening. However,
Caco-2 cells were found to overexpress surface proteins (e.g., P-gp)
compared with the normal intestinal epithelial cells in vivo. To critically evaluate the challenge and suitability of Caco-2
cells, a GOC integrated with a carcinoembryonic antigen (CEA) biosensor
was developed. This three-electrode system electrochemical sensor
detects CEA by antigen–antibody specific binding, and it exhibits
high selectivity, excellent stability, and good reproducibility. Under
dynamic culturing in the GOC, Caco-2 cells exhibited an intestinal
villus-like structure and maintained tissue barrier integrity. Meanwhile,
CEA was discovered to be secreted from 0 to 0.22 ng/mL during the
10-day culturing of Caco-2 cells. Especially, CEA secretion increased
significantly with the differentiation of Caco-2 cells after 6 days
of culturing. The sustained high-level CEA secretion may induce cells
to avoid apoptotic stimuli, which faithfully reflects the efficacy
of a new drug and the mechanism of intestinal disease. Different kinds
of cell types (e.g., intestinal primary cells, stem cell-induced differentiation)
in the GOC should be attempted for drug screening in the future.