Acoustofluidic-mediated molecular delivery to human T cells with a three-dimensional-printed flow chamber
Acoustofluidic-mediated molecular delivery to human T cells with a three-dimensional-printed flow chamber
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DOI：
10.1121/10.0009054
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发表时间：
2021-12-01
影响因子：
2.4
通讯作者：
Kopechek, Jonathan A.
中科院分区：
文献类型：
--
作者：
Centner, Connor S.;Moore, John T.;Kopechek, Jonathan A.
基于细胞的疗法在治疗癌症和其他疾病方面引起了极大的兴趣。声流体技术正在开发中，以通过促进经由超声和微泡（MB）穿过质膜的快速分子递送来改进细胞疗法制造。在这项研究中，使用三维（3D）打印的声流体装置将荧光分子钙黄绿素递送到人类T细胞。在改变参数如MB面电荷、MB浓度、流动通道几何形状、超声压力和超声处理后的递送时间点后评估钙黄绿素的细胞内递送。与具有中性表面电荷的MB相比，具有阳离子表面电荷的MB在声流体处理期间引起钙黄绿素递送的统计学显著增加（p < 0.001）。与直线通道几何形状相比，同心螺旋通道几何形状的钙黄绿素递送显著更高（p < 0.001）。此外，与0- 3.8MPa之间的较低超声压力相比，在5.1MPa的增加超声压力下钙黄绿素递送显著增强（p < 0.001）。这些结果表明，3D打印的声流体装置可以显著增强生物分子向T细胞的细胞内递送，这可能是推进基于细胞的疗法的可行方法。
Cell-based therapies have garnered significant interest to treat cancer and other diseases. Acoustofluidic technologies are in development to improve cell therapy manufacturing by facilitating rapid molecular delivery across the plasma membrane via ultrasound and microbubbles (MBs). In this study, a three-dimensional (3D) printed acoustofluidic device was used to deliver a fluorescent molecule, calcein, to human T cells. Intracellular delivery of calcein was assessed after varying parameters such as MB face charge, MB concentration, flow channel geometry, ultrasound pressure, and delivery time point after ultrasound treatment. MBs with a cationic surface charge caused statistically significant increases in calcein delivery during acoustofluidic treatment compared to MBs with a neutral surface charge (p < 0.001). Calcein delivery was significantly higher with a concentric spiral channel geometry compared to a rectilinear channel geometry (p < 0.001). Additionally, calcein delivery was significantly enhanced at increased ultrasound pressures of 5.1 MPa compared to lower ultrasound pressures between 0-3.8 MPa (p < 0.001). These results demonstrate that a 3D-printed acoustofluidic device can significantly enhance intracellular delivery of biomolecules to T cells, which may be a viable approach to advance cell-based therapies.