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无标记惯性-铁磁流体动力学高通量高分辨率细胞分离。

Label-free inertial-ferrohydrodynamic cell separation with high throughput and resolution.

机构信息

Department of Chemistry, The University of Georgia, Athens, Georgia, USA.

FCS Technology LLC, Athens, Georgia, USA.

出版信息

Lab Chip. 2021 Jul 13;21(14):2738-2750. doi: 10.1039/d1lc00282a.

Abstract

Rapid and label-free separation of target cells from biological samples provided unique opportunity for disease diagnostics and treatment. However, even with advanced technologies for cell separation, the limited throughput, high cost and low separation resolution still prevented their utility in separating cells with well-defined physical features from a large volume of biological samples. Here we described an ultrahigh-throughput microfluidic technology, termed as inertial-ferrohydrodynamic cell separation (inertial-FCS), that rapidly sorted through over 60 milliliters of samples at a throughput of 100 000 cells per second in a label-free manner, differentiating the cells based on their physical diameter difference with ∼1-2 μm separation resolution. Through the integration of inertial focusing and ferrohydrodynamic separation, we demonstrated that the resulting inertial-FCS devices could separate viable and expandable circulating tumor cells from cancer patients' blood with a high recovery rate and high purity. We also showed that the devices could enrich lymphocytes directly from white blood cells based on their physical morphology without any labeling steps. This label-free method could address the needs of high throughput and high resolution cell separation in circulating tumor cell research and adoptive cell transfer immunotherapy.

摘要

快速且无需标记的靶细胞与生物样本分离为疾病诊断和治疗提供了独特的机会。然而,即使采用了先进的细胞分离技术,其有限的通量、高成本和低分离分辨率仍然限制了它们在从大量生物样本中分离具有明确物理特征的细胞方面的应用。在这里,我们描述了一种超高通量微流控技术,称为惯性-铁磁流体动力学细胞分离(inertial-FCS),它可以以 100,000 个细胞/秒的通量、无需标记的方式快速对超过 60 毫升的样品进行分类,基于其物理直径差异以约 1-2 μm 的分离分辨率对细胞进行区分。通过惯性聚焦和铁磁流体动力学分离的集成,我们证明了所得到的惯性-FCS 设备可以从癌症患者的血液中以高回收率和高纯度分离出有活力和可扩增的循环肿瘤细胞。我们还表明,该设备可以直接根据其物理形态从白细胞中富集淋巴细胞,而无需任何标记步骤。这种无需标记的方法可以满足循环肿瘤细胞研究和过继细胞转移免疫治疗中高通量和高分辨率细胞分离的需求。

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