한빛사논문
Seo Woo Songa, Su Deok Kima, Dong Yoon Ohb, Yongju Leea, Amos Chungwon Leec, Yunjin Jeonga, Hyung Jong Baed, Daewon Leee, Sumin Leea, Jiyun Kimf,* and Sunghoon Kwona,*
aDepartment of Electrical and Computer Engineering, Seoul National University, Seoul 08826, South Korea
bInstitutes of Entrepreneurial BioConvergence , Seoul National University, Seoul 08826, South Korea
cInterdisciplinary Program in Bioengineering, Seoul National University, Seoul 08826, South Korea
dDepartment of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
eNano Systems Institute, Seoul National University, Seoul 08826, South Korea
fSchool of Materials Science and Engineering, Ulsan National Institute of Science and Technology, Ulsan 44919, South Korea
S.W.S., S.D.K., J.K., and S.K. contributed equally to this work.
*To whom correspondence should be addressed.
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.
Keywords : drug‐laden hydrogel, encoded microparticle, high‐throughput screening, self‐assembly, sequential combination
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