Microfluidic Device for the Separation of Non-Metastatic (MCF-7) and Non-Tumor (MCF-10A) Breast Cancer Cells Using AC Dielectrophoresis

Summary

Breast cancer cells exhibit different dielectric properties compared to non-tumor breast epithelial cells. It has been hypothesized that, based on this difference in dielectric properties, the two populations can be separated for immunotherapy purposes. To support this, we model a microfluidic device to sort MCF-7 and MCF-10A cells.

Abstract

Dielectrophoretic devices are capable of the detection and manipulation of cancer cells in a label-free, cost-effective, robust, and accurate manner using the principle of the polarization of the cancer cells in the sample volume by applying an external electric field. This article demonstrates how a microfluidic platform can be utilized for high-throughput continuous sorting of non-metastatic breast cancer cells (MCF-7) and non-tumor breast epithelial cells (MCF-10A) using hydrodynamic dielectrophoresis (HDEP) from the cell mixture. By generating an electric field between two electrodes placed side-by-side with a micron-sized gap between them in an HDEP microfluidic chip, non-tumor breast epithelial cells (MCF-10A) can be pushed away, exhibiting negative DEP inside the main channel, while the non-metastatic breast cancer cells follow their course unaffected when suspended in cell medium due to having conductivity higher than the membrane conductivity. To demonstrate this concept, simulations were performed for different values of medium conductivity, and the sorting of cells was studied. A parametric study was carried out, and a suitable cell mixture conductivity was found to be 0.4 S/m. By keeping the medium conductivity fixed, an adequate AC frequency of 0.8 MHz was established, giving maximum sorting efficiency, by varying the electric field frequency. Using the demonstrated method, after choosing the appropriate cell mixture suspension medium conductivity and frequency of the applied AC, maximum sorting efficiency can be achieved.

Introduction

A malignant tumor that develops in and around the breast tissue is a frequent cause of breast cancer in women worldwide, causing a critical health problem¹. Breast tumors before metastasis can be treated through surgery if detected at an early stage, but if ignored, they can have severe implications on the patient's life by spreading to their lungs, brain, and bones. The treatments offered at later stages, such as radiation and chemical-based therapies, have severe side effects². Recent studies have reported that an early diagnosis of breast cancer reduces the mortality rate by 60%³. Hence, it....

Protocol

NOTE: The protocol here uses COMSOL, a multiphysics simulation software, to simulate the controlled sorting of non-metastatic breast cancer cells (MCF-7) and non-tumor breast epithelial cells (MCF-10A) using AC dielectrophoresis.

1. Chip design and parameter selection

1. Open multiphysics software and select Blank Model. Right-click on the Global Definitions and select Parameters. Import the parameters given in Table 1 into global definitions as a text file or enter the values individually.
2. Select Add Component from the h....

Results

Investigating the optimal operational parameters for effective DEP-based sorting of non-metastatic breast cancer (MCF-7) and non-tumor breast epithelial (MCF-10A) cells
To achieve a successful separation of non-metastatic breast cancer (MCF-7) and non-tumor breast epithelial (MCF-10A) cells with divergent dielectric properties when undergoing dielectrophoresis, their K factors should be distinct by keeping the applied frequency fixed^37,38. .......

Discussion

Microfluidic devices have been reported previously for cell culture, trapping, and sorting^47,52,53. The fabrication of these devices in the cleanroom is an expensive process, and it is imperative to quantify the output and efficiency of a proposed microfluidic device through CFD simulations. This study presents the design and simulations of an AC-dielectrophoretic microfluidic device for the continuous separation of non-metastat.......

Materials

Name	Company	Catalog Number	Comments
COMSOL	COMSOL		multiphysics simulation software