Demonstration of gut chip and QuadTC linked culture using estrogen as a model. A) Schematic overview of linked culture experiments. Gut chips are cultured to form villus structures followed by removal of estrogen from inlet media. ER+, MCF7 spheroids are grown for three days and then transitioned to estrogen‐free media. At day 7 of gut chip culture, spheroids are loaded into QuadTC and connected to gut chip circulatory effluent. Gut chips may be fed with model molecules, such as a fluorescently labeled estradiol, through the lumen compartment to model absorption and circulation of metabolites. B) Example of simple tubing interconnects to enable linked culture using a gut chip (left) and SCTC (right). C) Following two days of linked culture, significantly increased expression of GREB1, an estrogen‐responsive gene transcript, was detected in spheroids downstream of gut chips fed a fluorescently labeled estradiol, Estradiol Glow, *, p = 0.013, Welch's t‐test, n = 8–11 over two experiments.