High Aspect Ratio Sub-Micrometer Channels Using Wet Etching: Application to the Dynamics of Red Blood Cell Transiting through Biomimetic Splenic Slits
High Aspect Ratio Sub-Micrometer Channels Using Wet Etching: Application to the Dynamics of Red Blood Cell Transiting through Biomimetic Splenic Slits
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DOI：
10.1002/smll.201700967
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发表时间：
2017-08-25
期刊：
影响因子：
13.3
通讯作者：
Charrier, Anne
中科院分区：
文献类型：
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作者：
Gambhire, Priya;Atwell, Scott;Charrier, Anne
在脾过滤期间递送药物、散布癌细胞和红细胞（RBC）的纳米颗粒必须变形并穿过内衬血管的内皮细胞之间的亚微米和高纵横比间隙。颗粒/细胞通过这些狭缝状间隙的动力学仍然知之甚少，因为在与光学显微镜观察兼容的装置中具有生理尺寸的狭缝的体外再现需要昂贵的技术。在这里，新的微流体PDMS装置含有高纵横比狭缝与亚微米宽度的硅主模使用一个简单的，廉价的，高度灵活的方法结合标准的UV光刻和各向异性湿法蚀刻。这些装置能够揭示健康和患病红细胞在生理间质压力下挤压通过脾样狭缝（0.6-2 x 5-10 x 1.6-11 μ m（3））的新变形模式。在狭缝出口处，球形红细胞的细胞骨架似乎与脂质膜分离，而来自健康供体和镰状细胞病患者的红细胞在其前部显示出特殊的尖端。这些尖端在患者细胞中消失得慢得多，允许估计镰状细胞病中RBC细胞质粘度增加三倍。在狭缝中RBC隔离的时间和速率的测量允许量化球形红细胞RBC的大量捕获。
Nanoparticles delivering drugs, disseminating cancer cells, and red blood cells (RBCs) during splenic filtration must deform and pass through the sub-micrometer and high aspect ratio interstices between the endothelial cells lining blood vessels. The dynamics of passage of particles/cells through these slit-like interstices remain poorly understood because the in vitro reproduction of slits with physiological dimensions in devices compatible with optical microscopy observations requires expensive technologies. Here, novel microfluidic PDMS devices containing high aspect ratio slits with sub-micrometer width are molded on silicon masters using a simple, inexpensive, and highly flexible method combining standard UV lithography and anisotropic wet etching. These devices enabled revealing novel modes of deformations of healthy and diseased RBCs squeezing through splenic-like slits (0.6-2 x 5-10 x 1.6-11 mu m(3)) under physiological interstitial pressures. At the slit exit, the cytoskeleton of spherocytic RBCs seemed to be detached from the lipid membrane whereas RBCs from healthy donors and patients with sickle cell disease exhibited peculiar tips at their front. These tips disappeared much slower in patients' cells, allowing estimating a threefold increase in RBC cytoplasmic viscosity in sickle cell disease. Measurements of time and rate of RBC sequestration in the slits allowed quantifying the massive trapping of spherocytic RBCs.