Sorting cells by their density.
Sorting cells by their density.
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DOI：
10.1371/journal.pone.0180520
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Grover WH
中科院分区：
文献类型：
--
作者：
Norouzi N;Bhakta HC;Grover WH
按细胞类型分选细胞是生物研究和医学诊断中的重要能力。然而，大多数细胞分选技术依赖于标记或标签，其可能具有有限的可用性和特异性。通过不同的物理性质对不同的细胞类型进行分类是一种有吸引力的标签替代方案，因为所有细胞本质上都具有这些物理性质。但是一些物理特性，如细胞大小，在一种细胞类型中，细胞与细胞之间的差异很大;这使得很难仅根据它们的大小来识别和分类细胞。在这项工作中，我们通过密度连续地对不同的细胞类型进行分类，密度是一种物理特性，与其他物理特性相比，细胞类型内的细胞间差异要小得多（因此区分不同细胞类型的潜力更大）。我们使用包含水平流动的微米级密度梯度的3D打印微流体芯片来实现这一点。当细胞流过芯片时，地球的重力使每个细胞垂直移动到细胞密度与周围流体密度相匹配的点。当水平通道然后分裂时，具有不同密度的细胞被路由到不同的出口。作为概念验证，我们使用密度分选芯片按材料（聚乙烯和聚苯乙烯）对聚合物微珠进行分选，并按类型（白色血细胞和红细胞）对血细胞进行分选。该芯片将血液样品中的白色血细胞部分从0.1%（全血中）富集到近98%（芯片输出中），1000倍富集。任何拥有3D打印机的研究人员都可以轻松复制我们的密度分选芯片，并使用作为在线支持信息提供的设计文件在自己的研究中使用。此外，研究人员还可以在自己的应用中使用基于Python的仿真软件来模拟密度分选芯片的性能。该技术的简单性、分辨率和通量使其适用于在各种不同的研究和临床应用中分离复杂生物样品中甚至罕见的细胞类型。
Sorting cells by their type is an important capability in biological research and medical diagnostics. However, most cell sorting techniques rely on labels or tags, which may have limited availability and specificity. Sorting different cell types by their different physical properties is an attractive alternative to labels because all cells intrinsically have these physical properties. But some physical properties, like cell size, vary significantly from cell to cell within a cell type; this makes it difficult to identify and sort cells based on their sizes alone. In this work we continuously sort different cells types by their density, a physical property with much lower cell-to-cell variation within a cell type (and therefore greater potential to discriminate different cell types) than other physical properties. We accomplish this using a 3D-printed microfluidic chip containing a horizontal flowing micron-scale density gradient. As cells flow through the chip, Earth’s gravity makes each cell move vertically to the point where the cell’s density matches the surrounding fluid’s density. When the horizontal channel then splits, cells with different densities are routed to different outlets. As a proof of concept, we use our density sorter chip to sort polymer microbeads by their material (polyethylene and polystyrene) and blood cells by their type (white blood cells and red blood cells). The chip enriches the fraction of white blood cells in a blood sample from 0.1% (in whole blood) to nearly 98% (in the output of the chip), a 1000x enrichment. Any researcher with access to a 3D printer can easily replicate our density sorter chip and use it in their own research using the design files provided as online Supporting Information. Additionally, researchers can simulate the performance of a density sorter chip in their own applications using the Python-based simulation software that accompanies this work. The simplicity, resolution, and throughput of this technique make it suitable for isolating even rare cell types in complex biological samples, in a wide variety of different research and clinical applications.
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影响因子：
--
作者：
Patel, Kushang V.;Ferrucci, Luigi;Ershler, William B.;Longo, Dan L.;Guralnik, Jack M.
通讯作者：
Guralnik, Jack M.
DOI：
10.1073/pnas.92.3.860
发表时间：
1995-01-31
影响因子：
11.1
作者：
BECKER, FF;WANG, XB;GASCOYNE, PRC
通讯作者：
GASCOYNE, PRC
影响因子：
6
作者：
Allen, Larry A.;Felker, G. Michael;Mehra, Mandeep R.;Chiong, Jun R.;Dunlap, Stephanie H.;Ghali, Jalal K.;Lenihan, Daniel J.;Oren, Ron M.;Wagoner, Lynne E.;Schwartz, Todd A.;Adams, Kirkwood F., Jr.
通讯作者：
Adams, Kirkwood F., Jr.
DOI：
10.1073/pnas.1218806110
发表时间：
2013-05-07
影响因子：
11.1
作者：
Byun, Sangwon;Son, Sungmin;Manalis, Scott R.
通讯作者：
Manalis, Scott R.
影响因子：
2.8
作者：
Soohoo JR;Walker GM
通讯作者：
Walker GM