Scalable Multiplexed Drug‐Combination Screening Platforms Using 3D Microtumor Model for Precision Medicine,Small

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Scalable Multiplexed Drug‐Combination Screening Platforms Using 3D Microtumor Model for Precision Medicine
Small ( IF 13.0 ) Pub Date : 2018-09-21 , DOI: 10.1002/smll.201703617
Zhixiong Zhang ₁ , Yu-Chih Chen _{1,

2} , Sumithra Urs ₃ , Lili Chen ₁ , Diane M. Simeone ₃ , Euisik Yoon _{1,

4}

Affiliation

Cancer heterogeneity is a notorious hallmark of this disease, and it is desirable to tailor effective treatments for each individual patient. Drug combinations have been widely accepted in cancer treatment for better therapeutic efficacy as compared to a single compound. However, experimental complexity and cost grow exponentially with more target compounds under investigation. The primary challenge remains to efficiently perform a large‐scale drug combination screening using a small number of patient primary samples for testing. Here, a scalable, easy‐to‐use, high‐throughput drug combination screening scheme is reported, which has the potential of screening all possible pairwise drug combinations for arbitrary number of drugs with multiple logarithmic mixing ratios. A “Christmas tree mixer” structure is introduced to generate a logarithmic concentration mixing ratio between drug pairs, providing a large drug concentration range for screening. A three‐layer structure design and special inlets arrangement facilitate simple drug loading process. As a proof of concept, an 8‐drug combination chip is implemented, which is capable of screening 172 different treatment conditions over 1032 3D cancer spheroids on a single chip. Using both cancer cell lines and patient‐derived cancer cells, effective drug combination screening is demonstrated for precision medicine.

中文翻译：

使用3D微型肿瘤模型的可扩展多重药物组合筛选平台用于精密医学

癌症的异质性是该疾病的臭名昭著的标志，因此希望为每位患者量身定制有效的治疗方法。与单一化合物相比，药物组合已在癌症治疗中被广泛接受，以提供更好的治疗效果。但是，随着研究中更多目标化合物的出现，实验的复杂性和成本呈指数增长。首要的挑战仍然是使用少量患者的原始样本进行测试来有效地进行大规模药物组合筛选。此处报道了一种可扩展，易于使用，高通量的药物组合筛选方案，该方案可以筛选所有可能的成对药物组合，以筛选具有多种对数混合比的任意数量的药物。引入“圣诞树混合器”结构以在药物对之间产生对数浓度混合比，从而为筛选提供了较大的药物浓度范围。三层结构设计和特殊的进样口布置简化了简单的药物装载过程。作为概念验证，实现了8药组合芯片，该芯片能够在单个芯片上筛选1032个3D癌症球体中的172种不同治疗条件。同时使用癌细胞系和患者来源的癌细胞，已证明对精密医学有效的药物组合筛选。实施了8药组合芯片，该芯片能够在单个芯片上筛选1032个3D癌症球体中的172种不同治疗条件。同时使用癌细胞系和患者来源的癌细胞，已证明对精密医学有效的药物组合筛选。实施了8药组合芯片，该芯片能够在单个芯片上筛选1032个3D癌症球体中的172种不同治疗条件。同时使用癌细胞系和患者来源的癌细胞，已证明对精密医学有效的药物组合筛选。

更新日期：2018-09-21

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