UHF-Dielectrophoresis Crossover Frequency as a New Marker for Discrimination of Glioblastoma Undifferentiated Cells

Abstract

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.

Human Medulloblastoma Cell Lines: Investigating on Cancer Stem Cell-Like Phenotype

“…Importantly, we exploited a novel method to discriminate the cell differentiation status using real-time measurements in a microfluidic lab-on-chip (LOC) platform implemented in CMOS technology [31,59,60]. This method was proven to be an efficient approach to identify circulating tumor cells [61] and physiological cell changes [62].…”

“…This method was proven to be an efficient approach to identify circulating tumor cells [61] and physiological cell changes [62]. Notably, differentiated cells can be identified and separated from an undifferentiated subpopulation, on the basis of their different dielectric signature, which determines different crossover frequencies [31,63]. The ability to discriminate CSCs through this technique has been recently proved on CSCs enriched and non-enriched populations of two different glioblastoma cell lines (U87 and LN18), showing differences in the intracellular dielectric characteristics [31].…”

“…Potential differences in stemness features were analyzed by classical approaches as gene, protein, and flow cytometry analysis of specific stem cell markers. Furthermore, since physical characterization was recently reported as complementary to cell biological features, to identify CSCs, we used high-frequency dielectrophoresis (HF-DEP) crossover frequency, a label-free, accurate, fast, and low-cost diagnostic technique that exploits the polarization and consequent motion of bio-particles in an applied electric fields [31].…”

Parallel single‐cell optical transit dielectrophoresis cytometer

“…Although this is an effective analysis tool, it is highly manual, has low throughput, and is not easily automated. There is also a number of approaches that use DEP trapping to infer dielectric properties [27,41–43]. There are DEP trapping‐based systems to measure the dielectrophoretic collection rate [9,40].…”

“…However, cell repulsion (negative DEP, nDEP) cannot be quantified by this method and moreover, there is a need for a microscope, video camera, and complex image analysis. Trapping‐based DEP systems have the advantage of being scalable and have been demonstrated in complementary metal oxide semiconductor (CMOS) technology [43]. However, trapping is a slow process and also exposes the cells to electric field magnitudes that could alter the cell via processes such as electroporation and in many cases are limited to positive DEP (pDEP) [44].…”