AC electrokinetic isolation and detection of extracellular vesicles from dental pulp stem cells: Theoretical simulation incorporating fluid mechanics

Abstract

Extracellular vesicles (EVs) are cell‐derived nanoscale vesicles involved in intracellular communication and the transportation of biomarkers. EVs released by mesenchymal stem cells have been recently reported to play a role in cell‐free therapy of many diseases. However, the demand for better research tools to replace the tedious conventional methods used to study EVs is getting stronger. EVs' manipulation using alternating current (AC) electrokinetic forces in a microfluidic device has appeared to be a reliable and sensitive diagnosis and trapping technique. Given that different AC electrokinetic forces may contribute to the overall motion of particles and fluids in a microfluidic device, EVs' electrokinetic trapping must be examined considering all dominant forces involved depending on the experimental conditions. In this paper, AC electrokinetic trapping of EVs using an interdigitated electrode arrays is investigated. A 2D numerical simulation incorporating the two significant AC electrokinetic phenomena (Dielectrophoresis and AC electroosmosis) has been performed. Theoretical predictions are then compared with experimental results and allow for a plausible explanation of observations inconsistent with DEP theory. It is demonstrated that the inconsistencies can be attributed to a significant extent to the contribution of the AC electroosmotic effect.

Potential neuroprotective effect of stem cells from apical papilla derived extracellular vesicles enriched by lab-on-chip approach during retinal degeneration

“…Another aspect of the novelty of this work lies in the microelectromechanical micro uidics (MEMS) device that we exploit to enrich the precise population of small EVs. Our previous work characterized and designed the MEMS device capable of enrichment of sEVs 34 . Brie y, this device offers a label-free and relatively fast method to isolate and enrich particles using AC electrokinetic phenomena.…”

Microfluidic Strategies for Extracellular Vesicle Isolation: Towards Clinical Applications

“…The latter has been exploited by Davies et al in a device that takes advantage of the electrophoretic interaction with a pressure-driven filtration stage of porous polymer monolithic membranes (PPMs), which have variable size pores, to isolate vesicles from 240 µL of whole blood in two hours. In addition to DEP, other examples of electrokinetic phenomena already exploited to trap and concentrate vesicles are electrophoresis [102,103] or electro-osmosis [104,105]. For example, Cho et al developed a device to enrich plasma EVs by coupling a porous membrane with a dedicated electrode (Figure 4b), in order to remove free proteins and debris subjected to electrophoretic migration through 30 nm pores, with an efficiency of approximately 85% [106].…”

“…Electrokinetic force [98][99][100][101][102][103][104][105][106][107][152][153][154] Charge separation by electric fields Chemical: Fixed support Functionalized fixed support [108][109][110][111][112][113][114][115][116][117][118][119][120][121][122]130, EV capture by specific antibodies on fixed substrate Chemical: Floating Beads Magnetic beads [125][126][127][128][129][130][131][132][133][134][135][181][182][183][184][185][186] EV capture by specific antibodies on beads for magnetic manipulation…”