Microfluidics for Measuring Electrical Properties of Cells

Joel Voldman
Biological Microtechnology and BioMEMS Group
Research Laboratory of Electronics

When people get sick, many physiological changes occur in the body, from systemic temperature rises (e.g., fever) to changes in the makeup of blood (e.g., release of cytokines). Cells in the body also respond to disease, and increasing interest has focused on how electrical properties of cells in particular are altered due to disease. Biological cells consist of a relatively electrically insulating outer sheath covering a salt-water interior. Taken together, this sheath and the saltwater interior impart measurable electrical conductivity and permittivity to cells. These electrical properties are in turn dependent on the physiological state of the cell. This variability of a cell’s electrical properties with its state has motivated significant effort to develop methods to measure these properties and separate cells based upon them.

Cells are small (~?m), and one typically wants to measure lots of them (thousands to millions), requiring the development of sensitive and fast instrumentation. An additional challenge is to try to avoid artifacts introduced by variations in cell size across a population; one wishes to measure a cell’s intrinsic electrical properties, not its size.

Prof. Joel Voldman with EECS graduate student Michael Vahey in the Biological Microtechnology and BioMEMS Group lab.

Prof. Joel Voldman with EECS graduate student Michael Vahey in the Biological Microtechnology and BioMEMS Group lab.

Professor Joel Voldman and EECS graduate student Michael Vahey (pictured above in the lab), members of RLE and MTL, have developed the first electrical cell separator capable of sensitive and highthroughput operation. The approach takes advantage of a fairly simple idea, which is that if one places an object in a liquid of identical electrical properties, then the object becomes “electrically transparent,” similar to how a bead with refractive index matched to water would optically disappear when placed in water. In the electrical separation device (Figure 1B, below), cells to be separated, flow into a microfluidic channel containing an electrical conductivity gradient. Micropatterned electrodes on the channel bottom apply an electrical force pushing the cells across the channel (Figure 1A, below). As the cells are pushed across the channel, they sample different local liquid conductivities. When the cells reach the location in the channel where their electrical conductivity matches that of the local liquid, the cells become electrically transparent, the electrical force vanishes, and they are no longer pushed across the channel; instead they are swept downstream for collection. The team has used the device to separate a number of cell samples, ranging from beads to yeast to mammalian cells (Figure 1C).

(A) Schematic of iso-dielectric separation device, showing how a cell population enters the channel and is pushed across (to the right) a channel containing a liquid conductivity gradient (in gray) by the electrodes (gold) until its electrical properties match that of the liquid, whereupon it separates. (B) Image of the device. (C) Image showing separation of two populations of yeast (red and green) based upon their electrical properties.

(A) Schematic of iso-dielectric separation device, showing how a cell population enters the channel and is pushed across (to the right) a channel containing a liquid conductivity gradient (in gray) by the electrodes (gold) until its electrical properties match that of the liquid, whereupon it separates. (B) Image of the device. (C) Image showing separation of two populations of yeast (red and green) based upon their electrical properties.

Vahey and Voldman are now using the technology to investigate the fundamental basis of how genetic differences affect the electrical properties of cells, which will lead to the first systematic map of how biological properties correlate to electrical properties, leading to the day when measuring the electrical properties of cells can be used clinically.

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One Response to “Microfluidics for Measuring Electrical Properties of Cells”

  1. Sarah Rhodes says:

    Very interesting article. I am wondering how this relates to systemic overgrowth of yeast within the body and the increase in cases of systemic yeast infections.

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