1) Researchers developed a multiwell plate format for high-throughput dielectrophoresis measurements of cells. 2) The device contains tubular wells made of alternating layers of gold-coated copper electrodes and insulating polyimide. 3) Using this device, researchers can rapidly distinguish viable and nonviable yeast cells and measure drug effects on human cells by analyzing changes in the frequency spectra measured from each well.

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Research Profile: Bringing dielectrophoresis to the masses . . . of cells
Joe Alper
Anal. Chem., 80 (7), 2285-2285• DOI: 10.1021/ac086018q • Publication Date (Web): 01 April 2008
Downloaded from http://pubs.acs.org on April 29, 2009
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Bringing dielectrophoresis to the masses . . . of cells
Dielectrophoresis—the induced motion with 75-μm-thick polyimide. They then duce noise in the system, the research-
of particles in a nonuniform electric drill 1 mm holes spaced 2.25 mm apart ers analyze signal intensity only in the
field—can serve as a sensitive indicator on-center through the composite, bond outer 30% of the radius of each well, a
of subtle changes in the inner workings the laminate to a 1-mm-thick polyimide region that contains 64% of the total
of a cell, but the technique’s cumber- sheet to form the base of the wells, and volume.
some, one-off nature has relegated it coat the exposed copper with gold to In addition to the smaller “spectra-
to the sidelines as a useful tool for cell ensure biocompatibility. Finally, they chip” setup, which measures 23.5 ×
biology or drug discovery. In a 34 mm, the researchers are
paper published in AC (2008, using the same methods to
80, 2063–2068), collabora- build a larger “spectra-plate”
tors Kai Hoettges and Michael device that has 1536 wells ar-
Hughes and their colleagues ranged in clusters of 16, 32,
at the University of Surrey and 64 in different regions of
(U.K.) describe their version the plate. The 86 × 127 mm
of a multiwell plate format that spectra-plate is bonded to the
turns dielectrophoresis into a empty frame of a 96-well plate
rapid assay designed for use in with an eye toward eventual
high-throughput screening ap- use in commercial 1536-well
plications. “From start to fin- systems.
ish, we can run an entire series Using the spectra chip, the
of dielectrophoresis measure- researchers could distinguish
ments on 20 groups of 4 sets between viable and dead yeast
of cells in about 30 minutes cells, a standard assessment
using a stamp-sized device and A spectra-chip dielectrophoresis device with 20 sets of 4 wells. measure for dielectrophoresis.
a commercial [microwell] plate The close-up of an actual well (inset) shows the alternating lay- Moreover, using curve-fit-
and fluid-handling systems,” ers of gold-coated copper electrodes and polyimide insulating ting software on the measured
says Hughes. layers. frequency spectra, they could
In a typical dielectropho- determine the percentage of
resis experiment, cells are placed on a wire alternate layers of conducting ma- viable versus nonviable cells with an ac-
glass slide fitted with electrodes. When terial to opposing phases of an ac gen- curacy of 1%. The ability to do this sug-
an alternating current is applied to the erator. The wells are wired together in gests that array-based dielectrophoresis
electrodes, the cells move toward either clusters of four, with each cluster con- should be useful for conducting IC50
the positive or negative electrode, de- nected to its own ac generator. This assays.
pending on factors such as membrane configuration allows the researchers to Next, they tested the effects of three
surface charge, membrane capacitance, measure an entire frequency spectrum different ion channel blockers on a hu-
and conductivity of the cytoplasm. By in parallel by subjecting each set of four man leukemia cell line. The cells showed
varying the frequency of the alternat- wells to a unique ac frequency. distinct spectral changes after exposure
ing current and counting the number of This multilayer, tubular electrode to each of the three agents. The data
cells attracted to one pole or the other, configuration increases dramatically the also showed that two of the agents, 5-
researchers can create a dielectrophore- electric field strength within a given nitro-2-(3-phenylpropylamino)benzoic
sis spectrum that characterizes a given volume of fluid compared with a planar acid and verapamil, decreased cytoplas-
cell state. Perturbing the cells in any system, raising the dielectrophoretic mic conductance, whereas treatment
way, such as by adding a drug, changes force operating on the cells, explains with quinine increased it. In each case,
the spectrum. Hughes. Depending on the characteris- the amount by which the cytoplasmic
Hoettges, a clinical chemist, and tics of a given cell population, the cells conductance changed was as expected,
Hughes, a dielectrophoresis expert, move toward either the center or the given the known mechanisms of action
took this system and essentially rolled it outer edges of the well. And because for the drug. “We’re convinced that
into a tube, creating dielectrophoretic the well base is transparent, cell move- these multiwell systems will finally help
wells. They start by building a conduc- ments within each well can be mea- dielectrophoresis realize its potential in
tor–composite laminate comprising 12 sured by recording the light transmitted cell-based studies,” says Hughes. a
layers of 17-μm-thick copper interleaved through it with a video camera. To re- —Joe Alper
A p r i l 1 , 2 0 0 8 / A n a ly t i c a l C h e m i s t r y 2285