Dielectrophoresis is a powerful technique used to distinguish distinct cellular identities in heterogeneous cell populations and to monitor changes in the cell state without the need for biochemical tags, including live and dead cells. Recent studies in the past decade have indicated that dielectrophoresis can be used to discriminate the disease state of cells by exploring the differences in the dielectric polarizabilities of the cells. Factors controlling the dielectric polarizability are dependent on the conductivity and permittivity of the cell and the suspending medium, the cell morphology, the internal structure, and the electric double layer effects associated with the charges on the cell surface. Diseased cells, such as those associated with malaria, cancer, dengue, anthrax and human African trypanosomiasis, could be spatially trapped by positive dielectrophoresis or spatially separated from other healthy cells by negative dielectrophoretic forces. The aim of this review was to provide a better and deeper understanding on how dielectrophoresis can be utilized to manipulate diseased cells. This review compiles and compares the significant findings obtained by researchers in manipulating abnormal or unhealthy cells.
Electrical properties of biological cells are useful to distinguish cells, either in their homogenous or heterogenous populations. They provide insight into the health, geometry, growth, differentiation, function, and physiological state, including death of any biological cell, i.e., phenotype and genotype of a cell. These properties play an important role in designing various microfluidic chip-based diagnostic tools that utilize electric field gradients for cell movement. Reported studies over several decades have revealed that electrorotation, dielectric spectroscopy, and dielectrophoresis are the most common cell characterization techniques to obtain electrical parameters. However, in each of these characterization techniques, several advancements have been reported especially within the last decade. Details of these advances vary from sophisticated methods like grinding electrode materials and mixing them with polymer composites for use as electrorotation electrodes to simple targeted means like using biological cells itself as electrodes. These advances in technologies are very well discussed in this review. Sequentially, a complete description of the characterized electrical properties targeted to specific bioparticles of interest is presented. The main concepts of dielectrophoresis, electrorotation, and impedance cytometry are given alongside the generated spectra including their analyses for both single and multiple cells. Also, various methods of electrode design, spacing, and fabrication are adequately discussed. The materials used for fabricating the electrodes and their advancement over time with respect to the choice of the materials are also substantially addressed. Finally, with the growing trend observed within this time frame, the future direction of bioparticle characterization could be predicted.
Babesia species are obligate intraerythrocytic tick-borne protozoan parasites that are the etiologic agents of babesiosis, a potentially life-threatening, malaria-like illness in humans and animals. Babesia-infected people have been known to suffer from complications including liver problems, severe hemolytic anemia, and kidney failure. As reported by the Food and Drug Administration, 38% of mortality cases observed in transfusion recipients were associated with transfusion transmitted diseases of which babesiosis is the chief culprit. As of now, no tests have been licensed yet for screening blood donors for babesiosis. Current diagnostic tools for babesiosis including enzyme-linked immunosorbent assay, fluorescence in situ hybridization, and polymerase chain reaction are expensive and burdened with multifarious shortcomings. In this research, a low-cost, high-specificity, quick, and easy-to-use insulator-based dielectrophoretic diagnostic tool is developed for characterizing and concentrating Babesia-infected cells in their homogenous mixture with healthy cell population. In this work, a mixture of Babesia-infected (varying parasitemia) and healthy red blood cells (RBCs or erythrocytes) was exposed to non-uniform electric fields in a fabricated microfluidic platform to manipulate and sort the Babesia-infected cells within a minute. At DC voltage configurations of 10 V and 0/6 V in the inlet and the two outlet channels, respectively, the diseased cells were seen to flow in a direction different from the healthy RBCs. Bright field and fluorescence microscopy were utilized to present qualitative differentiation of the healthy erythrocytes from the infected cells. The proposed micro device platform was able to enrich RBCs from 0.1% to ∼70% parasitemia. This device, when finally developed into a point-of-care diagnostic chip, would enhance the detection of Babesia-infected erythrocytes and as well serve as a precursor to babesiosis vaccine development.
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.
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