Ma Wei-Yuan, Hsiung Lo-Chang, Wang Chen-Ho, Chiang Chi-Ling, Lin Ching-Hung, Huang Chiun-Sheng, Wo Andrew M
Institute of Applied Mechanics, National Taiwan University, Taipei, Taiwan.
Institute of Zoology, National Taiwan University, Taipei, Taiwan.
Sci Rep. 2015 Apr 13;5:9656. doi: 10.1038/srep09656.
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.
基于药物的治疗方法是癌症管理中使用最广泛的干预措施。对于从肿瘤样本中获取的少量细胞,个性化药物反应分析仍然具有内在的挑战性。我们展示了一种具有内置微间隙的96孔格式微流控板,在多次检测/洗涤操作过程中可保留高达99.2%的细胞,单次试剂测试仅需9000个细胞(即每个测试点1000个细胞×3个选定浓度×一式三份),可实现药物筛选并与传统自动化工作站兼容。MCF7和MDA-MB-231细胞系的结果表明,该设备与传统96孔板对照之间在剂量反应方面未发现统计学显著差异。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。由于对原发性癌细胞进行药物筛选必须考虑多种情况,例如悬浮/贴壁细胞类型以及稀有/丰富细胞的可用性,该设备即使对于细胞数量少的悬浮细胞也能实现高通量筛选,因为独特的微流控细胞捕获功能可确保在多次溶液交换方案中细胞得以保存。