In vitro drug screening systems for pharmacological targets have been studied as substitutes for whole-animal experiments. Cultured cells or tissues provide promising substitution models when coupled with technological innovations in micro total analysis systems. In this study, we focus on an intestinal drug absorption assay, as the oral route is most frequently used for drug administration. Pharmacological studies have reported the development of artificial vessels that include tubular structures. However, it is difficult to observe the insides of these tubes in situ. To address this problem, we developed a micro-device that uses a pneumatic balloon actuator (PBA) to open and close an artificial intestinal tract. A human colon carcinoma cell line (Caco-2) was cultivated on the flat surface of the micro-device for 7 days to form the inner cellular layer of an artificial intestinal tract with which to evaluate drug transport. The artificial intestinal tract was completely actuated from a flat plate to a circular tube via a PBA with a pressure of 65 kPa, and drugs were perfused at a flow rate of 0.05 mL min −1 into the tubular artificial intestinal tract for 1 h. Using the openable artificial intestinal tract, the in vitro absorption of calcein and Texas Red were successfully estimated as models of hydrophilic and hydrophobic drugs, respectively. The artificial intestinal tract enables the effective evaluation of the in vitro intestinal absorption of drug candidates and contributes to the reduction of costs incurred during the initial stage of drug development.
In this brief, we propose a new physical design technique for a subquarter micrometer system-on-a-chip (SoC). By optimizing the individual layer's routing grid space, coupling effects such as crosstalk noise, crosstalk-induced delay variations, and coupling power consumption are almost eliminated with little runtime penalty. Experiments are performed on the design of an image processing circuit using a subquarter micron CMOS process with multilayer interconnects. Simply by employing our proposed technique, the maximum delay and the power consumption can be decreased simultaneously by up to 15% and 10%, respectively, without any other process improvements.
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