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基于超高频介电泳的微流控芯片用于干性表型特征分析和胶质母细胞瘤细胞的鉴别

Microfluidic Lab-on-a-Chip Based on UHF-Dielectrophoresis for Stemness Phenotype Characterization and Discrimination among Glioblastoma Cells.

机构信息

XLIM-UMR 7252, University of Limoges/CNRS, 87060 Limoges, France.

CAPTuR-EA 3842, University of Limoges, 87025 Limoges, France.

出版信息

Biosensors (Basel). 2021 Oct 13;11(10):388. doi: 10.3390/bios11100388.

DOI:10.3390/bios11100388
PMID:34677344
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8534203/
Abstract

Glioblastoma (GBM) is one of the most aggressive solid tumors, particularly due to the presence of cancer stem cells (CSCs). Nowadays, the characterization of this cell type with an efficient, fast and low-cost method remains an issue. Hence, we have developed a microfluidic lab-on-a-chip based on dielectrophoresis (DEP) single cell electro-manipulation to measure the two crossover frequencies: in the low-frequency range (below 500 kHz) and in the ultra-high-frequency range (UHF, above 50 MHz). First, in vitro conditions were investigated. An U87-MG cell line was cultured in different conditions in order to induce an undifferentiated phenotype. Then, ex vivo GBM cells from patients' primary cell culture were passed through the developed microfluidic system and characterized in order to reflect clinical conditions. This article demonstrates that the usual exploitation of low-frequency range DEP does not allow the discrimination of the undifferentiated GBM cells from the differentiated one. However, the presented study highlights the use of UHF-DEP as a relevant discriminant parameter. The proposed microfluidic lab-on-a-chip is able to follow the kinetics of U87-MG phenotype transformation in a CSC enrichment medium and the cancer stem cells phenotype acquirement.

摘要

胶质母细胞瘤(GBM)是最具侵袭性的实体肿瘤之一,特别是由于存在癌症干细胞(CSC)。如今,用一种高效、快速且低成本的方法来对这种细胞类型进行特征描述仍然是一个问题。因此,我们开发了一种基于介电泳(DEP)的微流控片上实验室单细胞电操作技术,用于测量两个交叉频率:在低频范围(低于 500 kHz)和超高频范围(UHF,高于 50 MHz)。首先,研究了体外条件。将 U87-MG 细胞系在不同条件下培养,以诱导未分化表型。然后,将患者原代细胞培养的 GBM 细胞通过开发的微流控系统传递并进行特征描述,以反映临床情况。本文表明,通常对低频DEP 的利用不允许区分未分化的 GBM 细胞与分化的细胞。然而,本研究强调了使用 UHF-DEP 作为相关的鉴别参数。所提出的微流控片上实验室能够在 CSC 富集培养基中跟踪 U87-MG 表型转化的动力学和癌症干细胞表型获得。

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