Fish Capsules: A System for High-Throughput Screening of Combinatorial Drugs,Advanced Science

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Fish Capsules: A System for High-Throughput Screening of Combinatorial Drugs
Advanced Science ( IF 14.3 ) Pub Date : 2022-01-27 , DOI: 10.1002/advs.202104449
Minghui Tang ₁ , Xin Duan ₁ , Anqi Yang ₁ , Shijie He ₁ , Yajing Zhou ₁ , Yuxin Liu ₁ , Lu Zhang ₁ , Xuan Luo _{2,

3} , Peng Shi _{2,

3} , Honglin Li ₄ , Xudong Lin ₁

Affiliation

Large-scale screening of molecules heavily relies on phenotyping of small living organisms during preclinical development. However, deep profiling candidate therapeutics on whole animals typically requires laborious manipulations and anesthetic treatment using traditional techniques or automated tools. Here, a novel fish capsule system that combines automated zebrafish encapsulating technology and droplet microarray strategy for in vivo functional screening of mono/polytherapies is described. This platform enables automated, rapid zebrafish orientation and immobilization in agarose to generate large-scale fish capsules by using a microfluidic device. Based on the effect of discontinuous dewetting, the prompt trapping of fish capsules in the aqueous arrays is successfully demonstrate. This system provides the capability to integrate pharmaceutical treatments with real-time multispectral microscopic imaging in a simple, pipetting-free and highly parallel manner. Coupling with machine learning algorithms, a small library of compounds is screened and analyzed, and clues about how to exploit compound combinations as therapeutic candidates are obtained. It is believed that this proposed strategy can be readily applied to multiple fields and is especially useful in the exploration of combinatorial drugs with limited amounts of samples and resources to accelerate the identification of novel therapeutics for precision medicines.

中文翻译：

鱼胶囊：组合药物的高通量筛选系统

分子的大规模筛选在很大程度上依赖于临床前开发过程中小型生物体的表型分析。然而，对整个动物进行深入分析候选疗法通常需要使用传统技术或自动化工具进行费力的操作和麻醉治疗。在这里，描述了一种新颖的鱼胶囊系统，该系统结合了自动斑马鱼封装技术和液滴微阵列策略，用于单/多疗法的体内功能筛选。该平台通过使用微流体装置实现了斑马鱼在琼脂糖中的自动化、快速定位和固定化，以生成大型鱼胶囊。基于不连续去湿的效果，成功地证明了鱼胶囊在水阵列中的迅速捕获。该系统能够以简单、无移液和高度并行的方式将药物治疗与实时多光谱显微成像相结合。结合机器学习算法，筛选和分析一个小型化合物库，并获得有关如何利用化合物组合作为治疗候选者的线索。相信该策略可以很容易地应用于多个领域，特别适用于探索具有有限样本和资源的组合药物，以加速识别精准药物的新疗法。筛选和分析了一个小型化合物库，并获得了有关如何利用化合物组合作为治疗候选者的线索。相信该策略可以很容易地应用于多个领域，特别适用于探索具有有限样本和资源的组合药物，以加速识别精准药物的新疗法。筛选和分析了一个小型化合物库，并获得了有关如何利用化合物组合作为治疗候选者的线索。相信该策略可以很容易地应用于多个领域，特别适用于探索具有有限样本和资源的组合药物，以加速识别精准药物的新疗法。

更新日期：2022-01-27

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