Department of Electrical Engineering, Graduate Institute of Electronics Engineering, National Taiwan University, Taipei, Taiwan.
Department of Life Science, National Taiwan University, Taipei, Taiwan.
Sci Rep. 2019 Jul 12;9(1):10120. doi: 10.1038/s41598-019-46502-3.
Therapeutic drug synergism intervened in cancer treatments has been demonstrated to be more effective than using a single effector. However, it remains inherently challenging, with a limited cell count from tumor samples, to achieve potent personalized drug cocktails. To address the issue above, we herein present a nanodroplet cell processing platform. The platform incorporates an automatic nanodroplet dispenser with cell array ParaStamp chips, which were fabricated by a new wax stamping approach derived from laser direct writing. Such approach enables not only the on-demand de-wetting with hydrophobic wax films on substrates but also the mask-less fabrication of non-planar microstructures (i.e. no photolithography process). The ParaStamp chip was pre-occupied with anti-cancer drugs and their associate mixtures, enabling for the spatially addressable screening of optimal drug combinations simultaneously. Each droplet with a critical volume of 200 nl containing with 100 cells was utilized. Results revealed that the optimal combination reduces approximate 28-folds of conducted doses compared with single drugs. Tumor inhibition with the optimally selected drug combination was further confirmed by using PC-3 tumor-bearing mouse models. Together, the nanodroplet cell processing platform could therefore offer new opportunities to power the personalized cancer medicine at early-stage drug screening and discovery.
在癌症治疗中,药物协同作用已被证明比单一药物更有效。然而,从肿瘤样本中获得的细胞数量有限,这使得实现有效的个性化药物鸡尾酒仍然具有挑战性。为了解决上述问题,我们提出了一种纳米液滴细胞处理平台。该平台结合了自动纳米液滴分配器和细胞阵列 ParaStamp 芯片,该芯片是通过源自激光直写的新型蜡压印方法制造的。这种方法不仅可以按需对基底上的疏油蜡膜进行去湿,还可以实现非平面微结构的无掩模制造(即无需光刻工艺)。ParaStamp 芯片预先填充有抗癌药物及其相关混合物,能够同时进行空间寻址的最佳药物组合筛选。每个具有 200nl 关键体积的液滴包含 100 个细胞。结果表明,与单药相比,最佳组合降低了约 28 倍的药物浓度。使用 PC-3 荷瘤小鼠模型进一步证实了最佳选择的药物组合的肿瘤抑制作用。总之,纳米液滴细胞处理平台为早期药物筛选和发现阶段的个性化癌症医学提供了新的机会。