Dielectrophoretic-Field Flow Fractionation Analysis of Dielectric, Density, and Deformability Characteristics of Cells and Particles

Abstract

Dielectrophoretic field-flow fractionation (DEP-FFF) has been used to discriminate between particles and cells based on their dielectric and density properties. However, hydrodynamic lift forces (HDLF) at flow rates needed for rapid separations were not accounted for in the previous theoretical treatment of the approach. Furthermore, no method was developed to isolate particle or cell physical characteristics directly from DEP-FFF elution data. An extended theory of DEP-FFF is presented that accounts for HDLF. Using DS19 erythroleukemia cells as model particles with frequency-dependent dielectric properties, it is shown that the revised theory accounts for DEP-FFF elution behavior over a wide range of conditions and is consistent with sedimentation-FFF when the DEP force is zero. Conducting four elution runs under specified conditions, the theory allows for the derivation of the cell density distribution and provides good estimates of the distributions of the dielectric properties of the cells and their deformability characteristics that affect HDLF. The approach allows for rapid profiling of the biophysical properties of cells, the identification and characterization of subpopulations and the design of optimal DEP-FFF separation conditions. The extended DEP-FFF theory is widely applicable and the parameter measurement methods may be adapted easily to other types of particles.

Dielectrophoresis has broad applicability to marker-free isolation of tumor cells from blood by microfluidic systems

“…A heterogeneous mixture of cells, therefore, gives rise to an elution profile that reflects the density, dielectric, and hydrodynamic lift distributions of the cells. 27,31,32 For a mammalian cell, Eq. (1) may be expressed 32 in terms of the height h at which the force balance occurs as…”

“…A, B, and C are constants defined by the chosen experimental conditions and depend on the acceleration due to gravity (g), the DEP microelectrode element width and spacing (d), the electric permittivity of the suspending medium (e s e 0 ), the frequency-dependent electrode polarization factor (Pðf Þ), the applied DEP voltage (V) of alternating frequency (f ), the dynamic viscosity of the suspending medium (g), and the shear rate of fluid flow at the DEP chamber floor ( _ v 0 ). 27,31,32 The hydrodynamic lift force term is based on the equation derived by Abkarian et al [33][34][35] from exhaustive studies on vesicles. These authors describe the mechanical deformation factor U, which accounts for variations in shape that impact hydrodynamic lift at different heights under Poisseiulle flow conditions.…”

“…To derive cell biophysical parameters from the three resulting cell elution profiles, we applied an approach modified from earlier work 27,31,32 employing MATLAB scripts. Starting with seed values of the crossover frequency f co ¼ 50 kHz and mechanical deformability factor U ¼ 0:1, (a) Cell elution times for the 15 kHz fixed frequency run were mapped to cell densities Dq based on f co and U; (b) Using the Dq value derived from (a), cell elution times for the "no DEP" run were mapped to determine revised cell mechanical deformability factors U; (c) Using the Dq and U values derived from (a) and (b), cell elution times for the "sweptfrequency" run were mapped to determine revised cell crossover frequencies f co .…”

Enhanced contactless dielectrophoresis enrichment and isolation platform via cell-scale microstructures

“…[1][2][3] Typically, samples from primary tumor sites consist of tumor-associated cells and cancer cells with differences in diverse properties such as gene expression, size, phenotype, and tumorigenic potential. A pure sample of specific subpopulations could be used to develop an optimal individualized treatment regimen for patients by targeting the most aggressive tumor cells and preventing tumor repopulation.…”

Particulate Phases Possibly Conveyed from Nuclear Waste Repositories by Groundwater

“…The version of the manufactured separation system for which the channel conveying the carrier liquid had an asymmetric shape (As-Fl-FFF) proved to be the most efficient, as it enabled nanoparticles ranging form 1 nm to 100 μm to be separated. As a general rule, an Inductively Coupled Plasma Mass Spectrometry (ICP-MS) is used as on-line detector, which allows reaching low detection limits, high sensitivity, large dynamic range and ability to simultaneously measure a large number of elements (Table 1) A large number of recent works contributing to the development of the FFF techniques significantly widened their applicability range in particle size analysis (Ahn et al, 2010;Baalousha et al, 2006;Dubascoux et al, 2008;Gascoyne, 2009;Isaacson & Bouchard, 2010;Otte et al, 2009;Pifer et al, 2011).…”