Spatially selective cell treatment and collection for integrative drug testing using hydrodynamic flow focusing and shifting.
Spatially selective cell treatment and collection for integrative drug testing using hydrodynamic flow focusing and shifting.
复制标题
DOI：
10.1371/journal.pone.0279102
复制
发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
Lee, Steve Seung-Young
中科院分区：
文献类型：
--
作者：
Wang, Xu T.;Zheng, Jingtian;Iyer, Maheshwar Adiraj;Szmelter, Adam Henry;Eddington, David;Lee, Steve Seung-Young
能够容易地产生和控制层流的流体动力聚焦促进了现有微流体培养装置中细胞的药物处理。然而，为了将这种装置的应用扩展到多参数药物测试，必须解决当前流体动力聚焦微流体的关键限制。在这里，我们描述了流体动力学聚焦和移位作为一种先进的微流体工具，用于空间选择性药物递送和基于细胞的综合药物测试。我们设计并制作了一个共流聚焦，三通道微流控装置与宽细胞培养室。通过控制样品和两侧溶液的入口流速，我们可以产生流体动力学聚焦和移位，其介导微流体装置中试剂和药物流的路径和宽度的精确调节。我们成功地验证了一个流体动力学聚焦和移位的方法，空间选择性地交付的二碘，亲脂性荧光团，和阿霉素，化疗药物，在我们的设备中的肿瘤细胞。此外，随后使胰蛋白酶EDTA溶液流过暴露于多柔比星流的细胞，允许我们选择性地收集经处理的细胞。我们的方法使下游高分辨率显微镜的细胞悬液，以确认核交付的阿霉素进入肿瘤细胞。在该装置中，我们还可以原位评估阿霉素对通过流体动力学流动聚焦和转移选择性处理的肿瘤细胞的细胞毒性作用。这些结果表明，流体动力学聚焦和移位能够实现快速和稳健的方法来空间处理细胞，然后在优化的微流体装置中收集细胞，为有效的药物筛选和发现提供综合分析工具。
Hydrodynamic focusing capable of readily producing and controlling laminar flow facilitates drug treatment of cells in existing microfluidic culture devices. However, to expand applications of such devices to multiparameter drug testing, critical limitations in current hydrodynamic focusing microfluidics must be addressed. Here we describe hydrodynamic focusing and shifting as an advanced microfluidics tool for spatially selective drug delivery and integrative cell-based drug testing. We designed and fabricated a co-flow focusing, three-channel microfluidic device with a wide cell culture chamber. By controlling inlet flow rates of sample and two side solutions, we could generate hydrodynamic focusing and shifting that mediated precise regulation of the path and width of reagent and drug stream in the microfluidic device. We successfully validated a hydrodynamic focusing and shifting approach for spatially selective delivery of DiI, a lipophilic fluorophore, and doxorubicin, a chemotherapeutic agent, to tumor cells in our device. Moreover, subsequent flowing of a trypsin EDTA solution over the cells that were exposed to doxorubicin flow allowed us to selectively collect the treated cells. Our approach enabled downstream high-resolution microscopy of the cell suspension to confirm the nuclear delivery of doxorubicin into the tumor cells. In the device, we could also evaluate in situ the cytotoxic effect of doxorubicin to the tumor cells that were selectively treated by hydrodynamic flow focusing and shifting. These results show that hydrodynamic focusing and shifting enable a fast and robust approach to spatially treat and then collect cells in an optimized microfluidic device, offering an integrative assay tool for efficient drug screening and discovery.
登录
查看更多内容
影响因子：
62.1
作者：
Huber D;Oskooei A;Casadevall I Solvas X;Andrew deMello;Kaigala GV
通讯作者：
Kaigala GV
影响因子：
4.6
作者：
Shih, Hsiu-Chen;Lee, Tse-Ang;Tung, Yi-Chung
通讯作者：
Tung, Yi-Chung
影响因子：
2.8
作者：
Aggarwal, Varun;Lele, Tanmay P.
通讯作者：
Lele, Tanmay P.
DOI：
10.1016/j.jconrel.2010.04.006
发表时间：
2010-09-01
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Cai S;Thati S;Bagby TR;Diab HM;Davies NM;Cohen MS;Forrest ML
通讯作者：
Forrest ML
影响因子：
4.3
作者：
Golden, Joel P.;Justin, Gusphyl A.;Nasir, Mansoor;Ligler, Frances S.
通讯作者：
Ligler, Frances S.