Breast cancer cell obatoclax response characterization using passivated‐electrode insulator‐based dielectrophoresis

Abstract

Inherent electrical properties of cells can be beneficial to characterize different cell lines and their response to experimental drugs. This paper presents a novel method to characterize the response of breast cancer cells to drug stimuli through use of off-chip passivated-electrode insulator-based dielectrophoresis (OπDEP) and the application of AC electric fields. This work is the first to demonstrate the ability of OπDEP to differentiate between two closely related breast cancer cell lines, LCC1 and LCC9 while assessing their drug sensitivity to an experimental anti-cancer agent, Obatoclax. Although both cell lines are derivatives of estrogen-responsive MCF-7 breast cancer cells, growth of LCC1 is estrogen independent and anti-estrogen responsive, while LCC9 is both estrogen-independent and anti-estrogen resistant. Under the same operating conditions, LCC1 and LCC9 had different DEP profiles. LCC1 cells had a trapping onset (crossover) frequency of 700 kHz and trapping efficiencies between 30–40%, while LCC9 cells had a lower crossover frequency (100 kHz) and showed higher trapping efficiencies of 40–60%. When exposed to the Obatoclax, both cell lines exhibited dose-dependent shifts in DEP crossover frequency and trapping efficiency. Here, DEP results supplemented with cell morphology and proliferation assays help us to understand the response of these breast cancer cells to Obatoclax.

On the recent developments of insulator‐based dielectrophoresis: A review

“…(I) Illustration of an EπDEP device depicting the embedded passivated electrodes (600 μm wide) and two columns of cylindrical insulating posts within. Reprinted with permission from , copyright (2013) Springer Nature. (J) Illustration of a cDEP channel and selective trapping of MDA‐MB‐231 human breast adenocarcinoma cells (blue color), while other similar cells (red color) are not trapped.…”

“…Another creative approach called embedded passivated‐electrode iDEP (EπDEP) was proposed by the Agah research group . This hybrid dielectrophoretic mode combines iDEP and eDEP as it employs devices that contain both electrodes and insulating structures.…”

Insulator Based Dielectrophoresis: Micro, Nano, and Molecular Scale Biological Applications

“…If the particle moves in the direction of a higher field gradient, the DEP type is called pDEP, and if the movement is away from high field gradient regions, it is termed nDEP. Both pDEP and nDEP have been utilized to manipulate cells and neutral particles [ 10 , 11 , 12 , 13 , 14 ], with various forms and shapes of electrodes, including planar [ 15 , 16 ], quadruple [ 17 , 18 ], and traveling wave [ 19 , 20 ] designs. The mechanism of particle manipulation using nDEP and pDEP is well understood, and numerous applications have been explored, including cell/particle manipulation [ 10 , 11 , 12 ], transport [ 21 ], separation [ 22 ], and sorting [ 23 ].…”

Passivated‐electrode insulator‐based dielectrophoretic separation of heterogeneous cell mixtures

“…One commonly cited method of DEP is field flow fractionation (FFF) DEP, which uses differences in the retention time of particles and DEP forces for the separation of mixtures. Although this technique has shown great promise for the identification of differently sized particles [16,19], the majority of these devices fall to the limitations of traditional electrode‐based DEP and insulator‐based DEP (iDEP) such as electrode fouling, electrolysis, and sample contamination [14,20]. Moreover, FFF DEP assays do not isolate cell populations in the microfluidic channels but rather create bands of cell populations to classify different groups.…”