Label‐free detection of multidrug resistance in K562 cells through isolated 3D‐electrode dielectrophoresis

Abstract

Dielectrophoresis (DEP), a technique used to separate particles based on different sizes and/or dielectric properties under nonuniform electric field, is a promising method to be applied in label-free, rapid, and effective cell manipulation and separation. In this study, a microelectromechanical systems-based, isolated 3D-electrode DEP device has been designed and implemented for the label-free detection of multidrug resistance in K562 leukemia cells, based on the differences in their cytoplasmic conductivities. Cells were hydrodynamically focused to the 3D-electrode arrays, placed on the side walls of the microchannel, through V-shaped parylene-C obstacles. 3D-electrodes extruded along the z-direction provide uniformly distributed DEP force through channel depth. Cell suspension containing resistant and sensitive cancer cells with 1:100 ratio was continuously flown through the channel at a rate of 10 μL/min. Detection was realized at 48.64 MHz, the cross-over frequency of sensitive K562 cells, at which sensitive cells flow with the fluid, while the resistant ones are trapped by positive DEP force. Device can be operated at considerably low voltages (<9 Vpp ). This is achieved by means of a very thin (0.5 μm) parylene coating on electrodes, providing the advantages offered by the isolation of electrodes from the sample, while the working voltage can still be kept low. Results prove that the presented DEP device can provide an efficient platform for the detection of multidrug resistance in leukemia, in a label-free manner.

Examination of the dielectrophoretic spectra of MCF7 breast cancer cells and leukocytes

“…These electrodes were placed in a parylene chamber to ease the experiments. Electrodes were isolated from the chamber by means of a thin parylene layer that eliminates electrolysis and cell damage without remarkable loss in the DEP force . Besides, the proposed microdevice structure was easily built using standard MEMS microfabrication processes.…”

“…The reciprocal V‐shaped planar electrodes placed at the bottom of the chamber provided the nonuniform electric field required to create the DEP force for cell movement. Electrodes were isolated from the chamber by means of a thin parylene layer that eliminates electrolysis and cell damage without remarkable loss in the DEP force . DEP spectrum devices were fabricated in METU‐MEMS cleanroom facilities (Ankara, Turkey).…”

Simultaneous and continuous particle separation and counting via localized DC-dielectrophoresis in a microfluidic chip

“…One popular approach is to integrate DEP with an impedance detection system. [6][7][8][9][10][11][12][13][14][15][16] The DEP force is utilized to enrich the target particles at the detection region or deplete the unwanted ones from the suspension. Due to the greatly concentrated sample, the detection sensitivity was improved.…”

“…Such a concept was successfully applied for the detection of bacteria, 6,7 DNA, 8,9,17 amyloid beta 10,16 and cancer cells. 15,16 There are some other types of detection means which were combined with DEP also. Do et al 18 designed a device which utilizes DEP to enrich and immobilize the target cells on an electrode covered with specic anti-EGFR biomarker.…”

An Insulating Constriction Dielectrophoresis Based Microfluidic Device for Protein Biomolecules Concentration

“…As a non-destructive particle manipulation method, dielectrophoresis (DEP) has been applied in microfluidic-based devices to manipulate and concentrate bioparticles, including cells [10][11][12], bacteria [13,14], viruses [15], DNA [16,17], and proteins [18,19]. Specifically, DEP occurs when the particles respond to an inhomogeneous electric field, where the particles in aqueous solution become polarizable thus exhibiting an induced dipole moment.…”