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.
Highlights
Noncommunicable diseases (NCDs) kill more than 36 million people annually representing 63% of global deaths [1]
We explore the use of peripheral blood mononuclear cells (PBMCs) to detect these cancerous cells since they are known to circulate in the peripheral blood of patients, especially when breast cancer is spread beyond the ducts into other parts of the breast tissues or other organs through blood [8]
Our results are categorized into sections demonstrating: (1) experimental evidence of electrophysiological characterization of both healthy PBMCs and breast cancer adenocarcinoma cells (ADCs), (2) validation of our microwell technique by comparing with studies from literature and (3) modeling and simulation parameters like meshing, stationary analysis, transient analysis
Summary
Noncommunicable diseases (NCDs) kill more than 36 million people annually representing 63% of global deaths [1]. A subset of NCDs, accounts for over 500,000 of these deaths [2] with an incidence of about 1.1 million new cases being reported per year [3]. When breast cancer cells break away from the original cancer, they can enter the blood or lymph vessels. Traveling through these vessels, cancer cells may settle in other areas of the breast or in the lymph nodes of the breast tissue, forming new tumors. Cancer cells may settle in other areas of the breast or in the lymph nodes of the breast tissue, forming new tumors These adenocarcinomas are the most difficult tumor to accurately identify the primary site [7]
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