Figure 1.

Large‐scale sequential combination screening by serial replacement of a drug‐releasing hydrogel microarray‐on‐a‐chip. a) Principle of rewiring cellular pathways by effective sequential drug treatment, and schematic illustration of multistep drug treatment in a highly parallel manner to find an efficient sequential drug pair. The drug‐releasing hydrogel microarray‐on‐a‐chip is combined with the cell chip to facilitate the multiplexed bioassay. Simple exchange of the microarray‐on‐a‐chip enables sequential delivery of heterogeneous drug combinations to corresponding microwells in a parallel manner. b) Schematic illustration of how the large‐scale, drug‐releasing hydrogel microarray‐on‐a‐chip is constructed by fully manual operation with a reduced workload. (i) Encoded drug‐laden microparticles (DLPs) are moved from the library to the assembly chip by one‐step pipetting. (ii) Encoded DLPs are simply assembled into microwells on the assembly chip by scraper‐assisted directed assembly. (iii) Array of DLPs is transferred to the transfer chip by stamping. (iv) Codes of encoded DLP are decoded automatically to identify which drug treatment was applied to each microwell.