Biomedical Engineering Reference
In-Depth Information
movement of cells during analysis. Potential advantages include longer transit times,
higher throughput, and potentially a wider variety of assay types than can be
performed on hydrodynamically focused cytometer systems.
2.3.3 Cellular Dielectric Properties
The specific membrane capacitance and conductance of mammalian cells reflect the
surface morphological complexities and barrier functions of the cell membrane,
providing an opportunity to use such dielectric properties to identify cell physio-
logical and pathological changes. Rapid and noninvasive cell characterization based
on electric and dielectric properties is of particular interest in novel approaches to
disease diagnosis and monitoring, basic research, and cell engineering. Dielectro-
phoresis (DEP) is the motion of neutral but polarizable particles subjected to
nonuniform electric fields. The surface properties of submicron particles dominate
their dielectrophoretic behavior as demonstrated, for example, by tobacco mosaic
virus and herpes simplex virus that can be manipulated and spatially separated in
a microelectrode array [55]. Dielectric properties can also be exploited for the
separation and controlled manipulation of micro- or nanostructures of living organ-
isms. Recent studies have advanced the application of DEP and chip-based devices
for human cells [56, 57]. The results point toward promising new possibilities for
early detection of malignancies in whole blood mixture using integrated DEP
devices.
Moving dielectrophoresis (mDEP) can be generated by sequentially energizing
a single electrode or an array of electrodes to form an electric field that moves cells
continuously along a microchannel [58]. DEP provides an increased measurement
precision and sensitivity in the detection of cells with different dielectric properties,
without any need for the use of labeling technology. It also allows for the use of much
reduced sample volumes when compared to traditional methods of cell analysis, such
as flow cytometry, potentially providing an efficient alternative for clinical use. DEP
differences could represent genetically determined differences (e.g., gene mutation or
deletion) and epigenetic effects (e.g., CpG methylation effects) of phenotypic
plasticity arising from the structural modification of cellular macromolecules such
as cell surface glycoproteins. There is a role for DEP-based devices in cell-based
analyses [59] and DEP has been used to differentiate drug accumulation phenotypes
in breast cancer cell lines using cytoplasmic conductivity [60], opening the areas of
drug discovery in which DEP could be linked with functional determinations of drug
micropharmacokinetics [61].
Negative dielectrophoretic force (nDEP force)-assisted positioning and electro-
rotation (ROT) measurements have been used to provide a quantitative analysis of
the toxic damage to cells with potential for the testing and development of new
pharmaceuticals [62, 63]. Such an approach provides a “holistic” view of the cellular
response and therefore is not dependent on the identification of a marker molecule as
a signature of change. Different cell properties such as size, membrane capacitance,
and cytoplasm conductivity can affect its “impedance spectrum” providing a
probeless approach for cell profiling using microfabricated cytometers [64]. The
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