One‐Step Generation of a Drug‐Releasing Hydrogel Microarray‐On‐A‐Chip for Large‐Scale Sequential Drug Combination Screening,Advanced Science

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One‐Step Generation of a Drug‐Releasing Hydrogel Microarray‐On‐A‐Chip for Large‐Scale Sequential Drug Combination Screening
Advanced Science ( IF 14.3 ) Pub Date : 2018-11-20 , DOI: 10.1002/advs.201801380
Seo Woo Song ₁ , Su Deok Kim ₁ , Dong Yoon Oh ₂ , Yongju Lee ₁ , Amos Chungwon Lee ₃ , Yunjin Jeong ₁ , Hyung Jong Bae ₄ , Daewon Lee ₅ , Sumin Lee ₁ , Jiyun Kim ₆ , Sunghoon Kwon ₁

Affiliation

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.

中文翻译：

用于大规模连续药物组合筛选的药物释放水凝胶芯片微阵列的一步生成

大规模筛选连续药物组合，其中细胞内途径的动态重新布线可带来有希望的治疗效果并改善生活质量，这对于个性化医疗至关重要，以确保现实的成本和时间要求以及更少的样品消耗。然而，大规模筛选需要昂贵且复杂的自动化液体处理系统，因此降低了临床医生或生物学家的可及性，限制了顺序药物组合在临床应用和学术研究中的全部潜力。在这里，提出了一个用于高通量组合药物筛选的小型化平台，该平台是“免移液”且可扩展用于顺序药物组合的筛选。该平台通过载药水凝胶微粒的自组装，采用并行和自下而上的方式形成异质药物释放水凝胶微阵列。这种方法消除了高通量大规模筛选中对液体处理系统和耗时操作的需求。此外，药物释放芯片微阵列的连续替换促进了每个微孔中以简单且高度并行的方式进行不同的药物交换，支持多步骤组合筛选的可扩展实施。该策略可应用于有限样本和资源的多种形式的组合药物筛选，这将拓宽精准医学大规模筛选的用途。

更新日期：2018-11-20

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