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ABSTRACT Accurate cancer cell analysis is critical across a wide range of medical fields, including clinical diagnostics, personalized medicine, drug development, and cancer research. The ability to rapidly analyze and characterize cancer cells is key to understanding tumor characteristics, developing targeted therapies, and improving patient outcomes. Microscale electrokinetic (EK) techniques have demonstrated their effectiveness and reliability as powerful tools for cell analysis, including cancerous cells. The applications of dielectrophoresis (DEP), an EK technique, in cancer cell analysis are discussed here with a focus on carcinomas, cancer that develops in epithelial tissue. In this review article, the working mechanism of DEP is first introduced, followed by an in‐depth review of recent studies published between 2015 and 2024. The concluding remarks section provides a summary of the key points discussed in this review and offers insights into potential future advancements in DEP‐based systems for analyzing cancerous cells. 

Nonlinear electrokinetic phenomena offer label-free, portable, and robust approaches for particle and cell assessment, including selective enrichment, separation, sorting, and characterization. The field of electrokinetics has evolved substantially since the first separation reports by Arne Tiselius in the 1930s. The last century witnessed major advances in the understanding of the weak-field theory, which supported developments in the use of linear electrophoresis and its adoption as a routine analytical technique. More recently, an improved understanding of the strong-field theory enabled the development of nonlinear electrokinetic techniques such as electrorotation, dielectrophoresis, and nonlinear electrophoresis. This review discusses the operating principles and recent applications of these three nonlinear electrokinetic phenomena for the analysis and manipulation of particles and cells and provides an overview of some of the latest developments in the field of nonlinear electrokinetics. 

Analyte migration order is a major aspect in all migration-based analytical separations methods. Presented here is the manipulation of the migration order of microparticles in an insulator-based electrokinetic separation. Three distinct particle mixtures were studied: a binary mixture of particles with similar electrical charge and different sizes, and two tertiary mixtures of particles of distinct sizes. Each one of the particle mixtures was separated twice, the first separation was performed under low voltage (linear electrokinetic regime) and the second separation was performed under high voltage (nonlinear electrokinetic regime). Linear electrophoresis, which discriminates particles by charge, is the dominant electrokinetic effect in the linear regime; while nonlinear electrophoresis, which discriminates particles by size and shape, is the dominant electrokinetic effect in the nonlinear regime. The separation results obtained with the three particle mixtures illustrated that particle elution order can be changed by switching from the linear electrokinetic regime to the nonlinear electrokinetic regime. Also, in all cases, better separation performances in terms of separation resolution (Rs) were obtained by employing the nonlinear electrokinetic regime allowing nonlinear electrophoresis to be the discriminatory electrokinetic mechanism. These findings could be applied to analyze complex samples containing bioparticles of interest within the micron size range. This is the first report where particle elution order is altered in an iEK system. 

An empirical model predicts particle retention time in iEK devices by integrating linear and nonlinear EK effects. 

Electrokinetic (EK) microsystems, which are capable of performing separations without the need for labeling analytes, are a rapidly growing area in microfluidics. The present work demonstrated three distinct binary microbial separations, computationally modeled and experimentally performed, in an insulator-based EK (iEK) system stimulated by DC-biased AC potentials. The separations had an increasing order of difficulty. First, a separation between cells of two distinct domains (Escherichia coli and Saccharomyces cerevisiae) was demonstrated. The second separation was for cells from the same domain but different species (Bacillus subtilis and Bacillus cereus). The last separation included cells from two closely related microbial strains of the same domain and the same species (two distinct S. cerevisiae strains). For each separation, a novel computational model, employing a continuous spatial and temporal function for predicting the particle velocity, was used to predict the retention time (tR,p) of each cell type, which aided the experimentation. All three cases resulted in separation resolution values Rs>1.5, indicating complete separation between the two cell species, with good reproducibility between the experimental repetitions (deviations < 6%) and good agreement (deviations < 18%) between the predicted tR,p and experimental (tR,e) retention time values. This study demonstrated the potential of DC-biased AC iEK systems for performing challenging microbial separations. 

This study proposes a strategy for improving the separation resolution of binary microparticle mixtures by modifying the post array arrangement in insulator-based electrokinetic devices. 

Bacteriophage therapy presents a promising avenue for combating antibiotic-resistant bacterial infections. Yet, challenges exist, particularly, the lack of a straightforward purification pipeline suitable for widespread application to many phage types, as some phages are known to undergo significant titer loss when purified via current techniques. Electrokinetic methods offer a potential solution to this hurdle, with nonlinear electrophoresis emerging as a particularly appealing approach due to its ability to discern both the size and shape of the target phage particles. Presented herein is the electrokinetic characterization of the mobility of nonlinear electrophoresis for two phages (SPN3US and ϕKZ) and three types of polystyrene nanoparticles. The latter served as controls and were selected based on their sizes and surface charge magnitude. Particle tracking velocimetry experiments were conducted to characterize the mobility of all five particles included in this study. The results indicated that the selected nanoparticles effectively replicate the migration behavior of the two phages under electric fields. Further, it was found that there is a significant difference in the nonlinear electrophoretic response of phages and that of host cells, as first characterized in a previous report, illustrating that electrokinetic-based separations are feasible. The findings from this work are the first characterization of the behavior of phages under nonlinear electrophoresis effects and illustrate the potential for the development of electrokinetic-based phage purification techniques that could aid the advancement of bacteriophage therapy.