Review article-dielectrophoresis: status of the theory, technology, and applications

Abstract

A review is presented of the present status of the theory, the developed technology and the current applications of dielectrophoresis (DEP). Over the past 10 years around 2000 publications have addressed these three aspects, and current trends suggest that the theory and technology have matured sufficiently for most effort to now be directed towards applying DEP to unmet needs in such areas as biosensors, cell therapeutics, drug discovery, medical diagnostics, microfluidics, nanoassembly, and particle filtration. The dipole approximation to describe the DEP force acting on a particle subjected to a nonuniform electric field has evolved to include multipole contributions, the perturbing effects arising from interactions with other cells and boundary surfaces, and the influence of electrical double-layer polarizations that must be considered for nanoparticles. Theoretical modelling of the electric field gradients generated by different electrode designs has also reached an advanced state. Advances in the technology include the development of sophisticated electrode designs, along with the introduction of new materials (e.g., silicone polymers, dry film resist) and methods for fabricating the electrodes and microfluidics of DEP devices (photo and electron beam lithography, laser ablation, thin film techniques, CMOS technology). Around three-quarters of the 300 or so scientific publications now being published each year on DEP are directed towards practical applications, and this is matched with an increasing number of patent applications. A summary of the US patents granted since January 2005 is given, along with an outline of the small number of perceived industrial applications (e.g., mineral separation, micropolishing, manipulation and dispensing of fluid droplets, manipulation and assembly of micro components). The technology has also advanced sufficiently for DEP to be used as a tool to manipulate nanoparticles (e.g., carbon nanotubes, nano wires, gold and metal oxide nanoparticles) for the fabrication of devices and sensors. Most efforts are now being directed towards biomedical applications, such as the spatial manipulation and selective separationenrichment of target cells or bacteria, high-throughput molecular screening, biosensors, immunoassays, and the artificial engineering of three-dimensional cell constructs. DEP is able to manipulate and sort cells without the need for biochemical labels or other bioengineered tags, and without contact to any surfaces. This opens up potentially important applications of DEP as a tool to address an unmet need in stem cell research and therapy.

Figure 1

Number of publications on DEP for the period 2000–2010. (The estimate for 2010 is based on the 110 papers published up to 1 May 2010.)

Figure 2

Classification of DEP publications since 1995, in terms of whether their content mainly addresses theory, technology (Tech), or applications (Appl), expressed as a percentage of the total number of papers published. The trend for 2010 suggests that the theory (5%) and technology (18%) have matured sufficiently for efforts to be directed mainly toward publication of applications (77%).

Figure 3

(a) The lines of electric potential associated with a dipole of moment qd. (b) The potential generated outside an uncharged dielectric sphere, polarized by an imposed field E, is identical to that produced by an induced dipole moment p. The resultant potential, when this dipole potential is superposed onto that of the original field E, must satisfy standard electrostatic boundary conditions at the surface of the sphere.

Figure 4

Schematic representation of how a nucleated cell can progressively be simplified to a homogeneous sphere of effective permittivity ${\epsilon }_p^{*}$, given by Eq. 15, that mimics the dielectric properties of the nucleated cell. The first step in simplification shown here is to represent the endoplasmic reticulum as a topographical feature that increases the effective capacitance of the nuclear envelope. The penultimate step represents the cell as a smeared-out cytoplasm surrounded by a membrane of complex permittivities ${\epsilon }_{\mathrm{cyt}}^{*}$ and ${\epsilon }_{\mathrm{mem}}^{*}$, respectively.

Figure 5

Solid line: DEP response modeled for a viable cell normalized against the DEP response for a sphere composed of the same electrolyte as the cell cytoplasm. With increasing frequency the cell’s DEP behavior approaches that of the conducting sphere, making the transition from negative to positive DEP at the “cross-over” frequency f_xo. Dashed line: DEP response for a larger cell (radius R2>R1). The cross-over frequency f_xo is sensitive to cell size, but the cross-over at the higher frequency f_hxo is not sensitive to cell size (with all other dielectric factors remaining constant).

Figure 6

DEP response modeled for a viable cell for two values of the conductivity of the suspending medium. The DEP cross-over frequency f_xo increases with increasing medium conductivity, but the high-frequency cross-over f_hxo is not sensitive to the medium conductivity.

Figure 7

Examples of axial and nonaxial multipoles constructed from evenly spaced point charges (Ref. , pp. 176–183). The axial quadrupole is constructed by adding a moment +qd to an original negative moment −qd, a distance d from an initial negative moment −qd located at the origin. The axial octupole is created by repeating this exercise with two quadrupoles.

Figure 8

A spherical particle trapped (left) by quadrupole polynomial electrodes (Ref. 41) and (right) in a 3Dl eight electrode field cage (Ref. 46). The field acting along the axis of symmetry in these two electrode assemblies is zero, and so no dipole moment can be induced in the particles. Higher-order moments are induced and account for the DEP forces.

Figure 9

(a) The interdigitated, castelled, electrode design for observing both positive and negative DEP collection of particles (Ref. 74). Particles collecting in the diamond-shaped areas on the electrodes are driven there by hydrodynamic fluid flow (Ref. 80). (b) Viable yeast cells collecting by positive DEP into pearl chains, and (stained) nonviable cells collecting by negative DEP into triangular aggregations levitated above the electrode plane (e.g., Ref. 49, 50).

Figure 10

(a) Particles focused into narrow bands of flow in an interdigitated, castellated, electrode system (e.g., Ref. 76). (b) A modified interdigitated, castellated design for separating particles according to their size into separate fluid flow streams (Ref. 77).

Figure 11

A traveling-wave DEP junction, fabricated by laser ablation, for the separation or bringing together of different particles types (Ref. 102).

Figure 12

(a) The DEP funnel electrode design for focusing and concentrating particles in a flowing aqueous suspension (based on Ref. 108). This design has been exploited in a particle sorting device described by Kralj et al. (Ref. 110) and an on-chip molecular library screening device (Ref. 202). (b) An electrodeless DEP particle trap formed by a dielectric constriction, etched into a quartz plate, for creating local and large field gradients for DEP (Ref. 122). This design has been used to concentrate and pattern DNA (Refs. 122, 123) and to design assays based on DNA hybridization (Refs. 124, 125).