One‐Step Generation of a Drug‐Releasing Hydrogel Microarray‐On‐A‐Chip for Large‐Scale Sequential Drug Combination Screening. Issue 3 (20th November 2018)

• Record Type: Journal Article
• Authors: Song, Seo Woo; Kim, Su Deok; Oh, Dong Yoon; Lee, Yongju; Lee, Amos Chungwon; Jeong, Yunjin; Bae, Hyung Jong; Lee, Daewon; Lee, Sumin; Kim, Jiyun; Kwon, Sunghoon
• Is Part Of: Advanced science. Volume 6:Issue 3(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-11-20
• Subjects: drug‐laden hydrogel -- encoded microparticle -- high‐throughput screening -- self‐assembly -- sequential combination; Science -- Periodicals; 505
• DOI: 10.1002/advs.201801380
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: Large‐scale screening of sequential drug combinations, wherein the dynamic rewiring of intracellular pathways leads to promising therapeutic effects and improvements in quality of life, is essential for personalized medicine to ensure realistic cost and time requirements and less sample consumption. However, the large‐scale screening requires expensive and complicated liquid handling systems for automation and therefore lowers the accessibility to clinicians or biologists, limiting the full potential of sequential drug combinations in clinical applications and academic investigations. Here, a miniaturized platform for high‐throughput combinatorial drug screening that is "pipetting‐free" and scalable for the screening of sequential drug combinations is presented. The platform uses parallel and bottom‐up formation of a heterogeneous drug‐releasing hydrogel microarray by self‐assembly of drug‐laden hydrogel microparticles. This approach eliminates the need for liquid handling systems and time‐consuming operation in high‐throughput large‐scale screening. In addition, the serial replacement of the drug‐releasing microarray‐on‐a‐chip facilitates different drug exchange in each and every microwell in a simple and highly parallel manner, supporting scalable implementation of multistep combinatorial screening. The proposed strategy can be applied to various forms of combinatorial drug screening with limited amounts of samples and resources, which will broaden the use of the large‐scale screening for precision medicine. Abstract : A high‐throughput, pipetting‐free platform for screening sequential combinatorial drugs is presented. Self‐assembly of encoded drug‐laden microparticles enables simple generation of large‐scale drug microarrays, and sequential replacement of drug chips achieves multistep drug treatment. Superior to previous miniaturized screening platforms, no automatic liquid handler is required for the whole process. Screening of sequential drug combinations against triple‐negative breast cancer is demonstrated.