A novel 96well-formatted micro-gap plate enabling drug response profiling on primary tumour samples.

A novel 96well-formatted micro-gap plate enabling drug response profiling on primary tumour samples.
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一种新型的96固有形式的微间隙板,可在原发性肿瘤样品上进行药物反应分析。

DOI:
10.1038/srep09656
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发表时间:
2015-04-13
期刊:
影响因子:
4.6
通讯作者:
Wo AM
Wo AM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ma WY;Hsiung LC;Wang CH;Chiang CL;Lin CH;Huang CS;Wo AM

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基于药物的治疗是癌症管理中最广泛使用的干预措施。由于肿瘤样本细胞计数低,个性化药物反应分析仍然具有固有的挑战性。我们提出了一个96格式良好的微流控板,内置微间隙,在多次分析/洗涤操作中保留高达99.2%的细胞,单试剂测试只需要9000个细胞(即每个测试点1000个细胞× 3个选定的浓度×三次),实现药物筛选和与传统自动化工作站的兼容性。对MCF7和MDA-MB-231细胞株的实验结果显示,该装置与常规96孔板对照的剂量效应无统计学意义。在该设备中测试的乳腺癌患者的原发性肿瘤样本也显示出良好的IC50预测。由于原发癌细胞的药物筛选必须考虑广泛的情况,例如悬浮/附着细胞类型和罕见/丰富的细胞可用性,该设备即使对细胞计数低的悬浮细胞也能进行高通量筛选,因为其标志性的微流体细胞捕获功能确保了细胞在多种溶液交换协议中的保存。
Drug-based treatments are the most widely used interventions for cancer management. Personalized drug response profiling remains inherently challenging with low cell count harvested from tumour sample. We present a 96well-formatted microfluidic plate with built-in micro-gap that preserves up to 99.2% of cells during multiple assay/wash operation and only 9,000 cells needed for a single reagent test (i.e. 1,000 cells per test spot x 3 selected concentration x triplication), enabling drug screening and compatibility with conventional automated workstations. Results with MCF7 and MDA-MB-231 cell lines showed that no statistical significance was found in dose-response between the device and conventional 96-well plate control. Primary tumour samples from breast cancer patients tested in the device also showed good IC50 prediction. With drug screening of primary cancer cells must consider a wide range of scenarios, e.g. suspended/attached cell types and rare/abundant cell availability, the device enables high throughput screening even for suspended cells with low cell count since the signature microfluidic cell-trapping feature ensures cell preservation in a multiple solution exchange protocol.
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