Massively-Parallelized, Deterministic Mechanoporation for Intracellular Delivery.
Massively-Parallelized, Deterministic Mechanoporation for Intracellular Delivery.
复制标题
DOI：
10.1021/acs.nanolett.9b03175
复制
发表时间：
2020-02-12
期刊：
影响因子：
10.8
通讯作者：
Rao MP
中科院分区：
文献类型：
--
作者：
Dixit HG;Starr R;Dundon ML;Pairs PI;Yang X;Zhang Y;Nampe D;Ballas CB;Tsutsui H;Forman SJ;Brown CE;Rao MP
基于质膜穿孔的微流控细胞内给药方法在生物和医学的广泛应用中显示出解决传统细胞工程技术局限性的前景。然而，在许多这些方法中，分配过程固有的随机性往往导致在传递效率和细胞生存能力之间的权衡，从而潜在地限制了它们的用途。在这里，我们提出了一种新的微流控器件概念，通过为整体细胞的确定性机械操作(DMP)提供机会来减轻这种权衡。这是通过在基于吸入的捕获过程中每个细胞撞击到单个针状穿透器上实现的，然后一旦细胞通过反向流动被释放，外源货物就通过产生的膜孔扩散地流入。大规模平行化可以实现高通量操作，而单位点穿孔允许在难以转染的细胞中传递小分子和大分子货物，其效率和存活率都超过了传统和新兴的转基因技术。因此，DMP显示出在总体上推进细胞工程实践，特别是工程细胞产品制造的前景。
Microfluidic intracellular delivery approaches based on plasma membrane poration have shown promise for addressing the limitations of conventional cellular engineering techniques in a wide range of applications in biology and medicine. However, the inherent stochasticity of the poration process in many of these approaches often results in a trade-off between delivery efficiency and cellular viability, thus potentially limiting their utility. Herein, we present a novel microfluidic device concept that mitigates this trade-off by providing opportunity for deterministic mechanoporation (DMP) of cells en masse. This is achieved by the impingement of each cell upon a single needle-like penetrator during aspiration-based capture, followed by diffusive influx of exogenous cargo through the resulting membrane pore, once the cells are released by reversal of flow. Massive parallelization enables high throughput operation, while single-site poration allows for delivery of small and large-molecule cargos in difficult-to-transfect cells with efficiencies and viabilities that exceed both conventional and emerging transfection techniques. As such, DMP shows promise for advancing cellular engineering practice in general and engineered cell product manufacturing in particular.
登录
查看更多内容
影响因子：
7.8
作者：
McNeil, PL;Steinhardt, RA
通讯作者：
Steinhardt, RA
影响因子：
19
作者：
Elnathan, Roey;Delalat, Bahman;Voelcker, Nicolas H.
通讯作者：
Voelcker, Nicolas H.
影响因子：
4.6
作者：
Meacham JM;Durvasula K;Degertekin FL;Fedorov AG
通讯作者：
Fedorov AG
影响因子：
17.1
作者：
Peng, Jinliang;Garcia, Mitch Andre;Choi, Jin-sil;Zhao, Libo;Chen, Kuan-Ju;Bernstein, James R.;Peyda, Parham;Hsiao, Yu-Sheng;Liu, Katherine W.;Lin, Wei-Yu;Pyle, April D.;Wang, Hao;Hou, Shuang;Tseng, Hsian-Rong
通讯作者：
Tseng, Hsian-Rong
影响因子：
5.2
作者：
Lakshmipathy, U;Pelacho, B;Verfaillie, CM
通讯作者：
Verfaillie, CM