Selective trapping of single mammalian breast cancer cells by insulator-based dielectrophoresis

Abstract

The trapping or immobilization of individual cells at specific locations in microfluidic platforms is essential for single cell studies, especially those requiring cell stimulation and downstream analysis of cellular content. Selectivity for individual cell types is required when mixtures of cells are analyzed in heterogeneous and complex matrices, such as the selection of metastatic cells within blood samples. Here, we demonstrate a microfluidic device based on direct current (DC) insulator-based dielectrophoresis (iDEP) for selective trapping of single MCF-7 breast cancer cells from mixtures with both mammalian peripheral blood mononuclear cells (PBMC) as well MDA-MB-231 as a second breast cancer cell type. The microfluidic device has a teardrop iDEP design optimized for the selective capture of single cells based on their differential DEP behavior under DC conditions. Numerical simulations adapted to experimental device geometries and buffer conditions predicted the trapping condition in which the dielectrophoretic force overcomes electrokinetic forces for MCF-7 cells, whereas PBMCs were not trapped. Experimentally, selective trapping of viable MCF-7 cells in mixtures with PBMCs was demonstrated in good agreement with simulations. A similar approach was also executed to demonstrate the selective trapping of MCF-7 cells in a mixture with MDA-MB-231 cells, indicating the selectivity of the device for weakly invasive and highly invasive breast cancer cells. The DEP studies were complemented with cell viability tests indicating acceptable cell viability over the course of an iDEP trapping experiment.

Experimental and theoretical study of dielectrophoretic particle trapping in arrays of insulating structures: Effect of particle size and shape

“…15 and 16 is intuitive: it represents that the velocities vectors are equal in magnitude but have opposite directions. While other authors have similar derivations for this trapping condition, we found this representation to be simpler to understand. For instance, in the case where particles exhibit negative DEP, the DEP mobility is less than zero.…”

“…Thus, the mobilities ratio in Eqs. 15 and 16 is less than zero and the trapping condition becomes the same as others reported in the literature : …”

A Numerical Approach for Dielectrophoretic Characterization and Separation of Human Hematopoietic Cells

“…Therefore, our model might be improved further to provide more realistic cellular dielectric models. The more accurate and precise cellular data gained, the smarter DEP devices and experimental conditions might be 2.8 [27] 3.29 [28] 3.29 [28] 7 [29] Membrane thickness (d, nm) 4.5 [25] 7.5 [30] 7.5 [30] 7 [29] Medium conductivity (σm, S/m) 5.6x 10 -5 [32] 1x10 -6 [33] Membrane permittivity (ℇmem, F/m) 4.44ℇ0 [31] 8.89ℇ0 [28] 10.67ℇ0 [28] 12.5ℇ0 [29] Cytoplasm conductivity (σint, S/m) 0.31 [31] 0.65 [28] 0.73 [28] 0.5 [29] Cytoplasm permittivity (ℇint, F/m) 59ℇ0 [31] 103.9ℇ0 [28] 154.4ℇ0 [28] 50ℇ0 [29] Measured surface area of the cells (A, µm 2 ) --265 [34] 280 [35] Membrane folding factor (Ф) 1 [27] 1.22 [36] 1.94 0.45 designed. Thus, complex biological interactions might be uncovered and applied to precision medicine in the near future.…”

Microfluidic dielectrophoretic sorter using gel vertical electrodes

“…Proposed alternatives include DEP devices employing various forms of insulating barriers to sculpt the electric field; these DEP devices are known as insulator-based dielectrophoresis (iDEP), electrodeless dielectrophoresis (eDEP), or contactless dielectrophoresis (cDEP) devices. 58,[62][63][64][65][66][67][68] In cDEP devices, planar electrodes are isolated from the main flow channel by thin polydimethylsiloxane (PDMS) walls. When the device is activated, field lines emanate from the electrodes towards the walls: these thin walls then translate these field lines into a vertically uniform electric field in the main channel via their capacitive properties.…”