The classic theory of direct-current (DC) insulator-based dielectrophoresis (iDEP) considers that, in order to elicit particle trapping, dielectrophoretic (DEP) velocity counterbalances electrokinetic (EK) motion, that is, electrophoresis (EP) and electro-osmotic flow (EOF). However, the particle velocity DEP component requires empirical correction factors (sometimes as high as 600) to account for experimental observations, suggesting the need for a refined model. Here, we show that, when applied to particle suspensions, a high-magnitude DC uniform electric field induces nonlinear particle velocities, leading to particle flow reversal beyond a critical field magnitude, referred to as the EK equilibrium condition. We further demonstrate that this particle motion can be described through an exploratory induced-charge EP nonlinear model. The model predictions were validated under an insulator-based microfluidic platform demonstrating predictive particle trapping for three different particle sizes (with an estimation error < 10%, not using correction factors). Our findings suggest that particle motion and trapping in “DC-iDEP” devices are dominated by EP and EOF, rather than by DEP effects.

Exosomes are nanovesicles secreted by most cellular types that carry important biochemical compounds throughout the body with different purposes, playing a preponderant role in cellular communication. Because of their structure, physicochemical properties and stability, recent studies are focusing in their use as nanocarriers for different therapeutic compounds for the treatment of different diseases ranging from cancer to Parkinson's disease. However, current bioseparation protocols and methodologies are selected based on the final exosome application or intended use and present both advantages and disadvantages when compared among them. In this context, this review aims to present the most important technologies available for exosome isolation while discussing their advantages and disadvantages and the possibilities of being combined with other strategies. This is critical since the development of novel exosome‐based therapeutic strategies will be constrained to the effectiveness and yield of the selected downstream purification methodologies for which a thorough understanding of the available technological resources is needed.

Exosomes are a specific subpopulation of extracellular vesicles that have gained interest because of their many potential biomedical applications. However, exosome isolation and characterization are the first steps toward designing novel applications. This work presents a direct current−insulator-based dielectrophoretic (DC-iDEP) approach to simultaneously capture and separate exosomes by size. To do so, a microdevice consisting of a channel with two electrically insulating post sections was designed. Each section was tailored to generate different nonuniform spatial distributions of the electric field and, therefore, different dielectrophoretic forces acting on exosomes suspended in solution. Side channels were placed adjacent to each section to allow sample recovery. By applying an electric potential difference of 2000 V across the length of the main channel, dielectrophoretic size-based separation of exosomes was observed in the device. Analysis of particle size in each recovered fraction served to assess exosome separation efficiency. These findings show that iDEP can represent a first step toward designing a high-throughput, fast, and robust microdevice capable of capturing and discriminating different subpopulations of exosomes based on their size.

Dielectrophoresis (DEP) is the motion of particles due to polarization effects in nonuniform electric fields. DEP has great potential for handling cells and is a non-destructive phenomenon. It has been utilized for different cell analysis, from viability assessments to concentration enrichment and separation. Insulator-based DEP (iDEP) provides an attractive alternative to conventional electrode-based systems; in iDEP, insulating structures are used to generate nonuniform electric fields, resulting in simpler and more robust devices. Despite the rapid development of iDEP microdevices for applications with cells, the fundamentals behind the dielectrophoretic behavior of cells has not been fully elucidated. Understanding the theory behind iDEP is necessary to continue the progress in this field. This work presents the manipulation and separation of bacterial and yeast cells with iDEP. A computational model in COMSOL Multiphysics was employed to predict the effect of direct current-iDEP on cells suspended in a microchannel containing an array of insulating structures. The model allowed predicting particle behavior, pathlines and the regions where dielectrophoretic immobilization should occur. Experimental work was performed at the same operating conditions employed with the model and results were compared, obtaining good agreement. This is the first report on the mathematical modeling of the dielectrophoretic response of yeast and bacterial cells in a DC-iDEP microdevice.

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