This paper introduces the first results of dielec-7 tric spectroscopy characterization of glioblastoma cells, measur-8 ing their crossover frequencies in the ultra-high-frequency range 9 (above 50 MHz) by dielectrophoresis (DEP) techniques. Exper-10 iments were performed on two glioblastoma lines U87-MG and 11 LN18 that were cultured following different conditions, in order 12 to achieve different phenotypic profiles. We demonstrate here that 13 the presented DEP electrokinetic method can be used to discrim-14 inate the undifferentiated from the differentiated cells. In this 15 study, microfluidic lab-on-chip systems implemented on bipolar-16 complementary oxide semiconductor technology are used allowing 17 single cell handling and analysis. Based on the characterizations 18 of their own intracellular features, both the selected glioblastoma 19 (GBM) cell lines cultured in distinct culture conditions have shown 20 clear differences of DEP crossover frequency signatures compared 21 to the differentiated cells cultured in a normal medium. These re-22 sults support the concept and validate the efficiency for cell char-23 acterization in glioblastoma pathology. 24 Index Terms-BiCMOS chip, biological cell manipulation, 25 glioblastoma cells, high frequency dielectrophoresis. 26 I. INTRODUCTION 27 G LIOBLASTOMA (GBM) is one of the most frequent and 28 the most aggressive tumors of the central nervous system.
This paper demonstrates the superior capabilities of Ultra-High Frequency dielectrophoresis (UHF-DEP) to sort populations of biological cells based on their intracellular dielectric characteristics. The proposed concept combines both hydrofluidic and repulsive dielectrophoresis forces into a microfluidic lab-on-chip to create a UHF-DEP cytometer. The main objective is to sort different types of cells using only negative dielectrophoresis principle. The idea is to select proper frequency for the applied electric field in order to produce different intensity of repulsive DEP forces related to the cell type. This sorting principle, without positive DEP, limits strong interaction of cells with the electric field, which could induce their permanent trapping during cytometer operation and reduces the efficiency of the cell sorting. Results presented in this paper demonstrate the capability of an effective sorting for mesenchymal cells.
This paper presents a microfluidic radiofrequency device operating at a few hundred MHz, which is able to sort biological cells. It uses a non-invasive and label-free technic based on intracellular dielectric specificities of biological cells. The sorting principle relies on a dynamic dielectrophoresis (DEP) deviation resulting from the interaction between a high frequency electric signal and the cell cytoplasm content. Driven in a microfluidic channel by a continuous flow, cells are individually deflected from their primary trajectories after having entered a non-uniform electric field generated by a microelectrode system. Designed with different slopes, these electrodes allow a selective guiding of cells to different outlets depending on the dielectrophoresis deviation efficiency. To allow a successful cell sorting, the intensity of deviation forces acting on cells is modulated according to the particle speed, the dielectrophoresis signal frequency and the electrode slope angles related to the Clausius-Mossotti factor of each cell. As proof of concept, experiments with cells from glioblastoma line were carried out, using different DEP signal frequencies to highlight system ability to sort cells from heterogeneous basal population into less disparate sub-populations.
In this paper, we introduce a method to exploit ultra-high dielectrophoresis (UHF-DEP) with a microfluidic radio frequency device able to sort biological cells by deflecting the trajectory of the targeted population in a continuous flow. This study highlights the capability of a high frequency lab-on-chip implemented UHF-DEP cytometer to isolate cancer stem cells (CSCs). Actually, CSCs sorting by an efficient, fast and low-cost method remains an issue. Above 20 MHz, the intracellular dielectric properties of cells determine the dielectrophoretic behavior of cells and is then very sensitive to the cell cytoplasm content. The proposed cell sorting principle exploits the combination of the fluidic drag and the repulsive dielectrophoretic forces in order to isolate CSCs hidden within differentiated cancer cells. We previously demonstrated the UHF-DEP behavior of cells, as a new type of electromagnetic biomarkers to discriminate cancer stem cells among a tumor population from colorectal cancer cell line.
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