Dielectric Characterization and Separation Optimization of Infiltrating Ductal Adenocarcinoma via Insulator-Dielectrophoresis

Abstract

The dielectrophoretic separation of infiltrating ductal adenocarcinoma cells (ADCs) from isolated peripheral blood mononuclear cells (PBMCs) in a ~1.4 mm long Y-shaped microfluidic channel with semi-circular insulating constrictions is numerically investigated. In this work, ADCs (breast cancer cells) and PBMCs’ electrophysiological properties were iteratively extracted through the fitting of a single-shell model with the frequency-conductivity data obtained from AC microwell experiments. In the numerical computation, the gradient of the electric field required to generate the necessary dielectrophoretic force within the constriction zone was provided through the application of electric potential across the whole fluidic channel. By adjusting the difference in potentials between the global inlet and outlet of the fluidic device, the minimum (effective) potential difference with the optimum particle transmission probability for ADCs was found. The radius of the semi-circular constrictions at which the effective potential difference was swept to obtain the optimum constriction size was also obtained. Independent particle discretization analysis was also conducted to underscore the accuracy of the numerical solution. The numerical results, which were obtained by the integration of fluid flow, electric current, and particle tracing module in COMSOL v5.3, reveal that PBMCs can be maximally separated from ADCs using a DC power source of 50 V. The article also discusses recirculation or wake formation behavior at high DC voltages (>100 V) even when sorting of cells are achieved. This result is the first step towards the production of a supplementary or confirmatory test device to detect early breast cancer non-invasively.

Dielectrophoretic ultra‐high‐frequency characterization and in silico sorting on uptake of rare earth elements by Cupriavidus necator

“…Equations associated with the physics and the boundary conditions employed for the DEP sorting of REE‐exposed C. necator from a heterogeneous mixture of both native and REE‐exposed C. necator using COMSOL are listed in Table 3. Zeta potential for PDMS is assumed to be –0.1 V [31]. A frequency domain study is used to solve for the physics contributing to electric currents at 100 kHz frequency.…”

“…It is a nondestructive and label/marker free electrokinetic technique to determine the dielectric signatures. Some of the popular methods that employ DEP to characterize and quantify the dielectric signatures of the cells are electrorotation [28–30], zero force method (also termed as crossover frequency method) [31, 32], DEP impedance spectra [33, 34], capture voltage spectra [35], and traveling wave [36, 37], which were well discussed in a recent review article by our research group [38].…”

Review: Dielectrophoresis in cell characterization

“…The reliance on fluorescent labelling of cells of this technique does increase sample preparation time and limits some of its applications. Recently, a 3D insulator‐based DEP (iDEP) device was used to characterize cells via DEP crossover frequency to optimize separation of infiltrating ductal adenocarcinoma cells (ADCs) from isolated PBMCs [93]. Here, they found total cell conductivity and permittivity for the adenocarcinoma cells (ADCs) to be 1.3 S/m and 69 ε o , respectively and for PMBCs, 0.67 S/m and 62 ε o , respectively.…”

Fine-Tuning Electrokinetic Injections Considering Nonlinear Electrokinetic Effects in Insulator-Based Devices

“…Particle streaming is particle migration primarily under linear EK effects, and particle trapping is when particle migration is stalled by nonlinear EK effects and bands of trapped particles are formed leading to significant enrichment [24]. The potential of iEK systems is significant, as their applicability for separating and analyzing valuable particles, including protein particles [25], nanovesicles [26], viruses [27], cells [8,28,29], and micro and nanoparticles [30,31], has been fully demonstrated. Given this new knowledge, the present study was focused on designing EK sample injection schemes for DC-iEK systems while considering the effects of nonlinear EP (known as the EP of the second kind or EP (3) ).…”