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Journal ArticleDOI

Separation of Submicron Bioparticles by Dielectrophoresis

01 Jul 1999-Biophysical Journal (The Biophysical Society)-Vol. 77, Iss: 1, pp 516-525
TL;DR: With electrode arrays fabricated using direct write electron beam lithography, it is shown that different types of submicron latex spheres can be spatially separated and it is demonstrated that tobacco mosaic virus and herpes simplex virus can be manipulated and spatially separation in a microelectrode array.
About: This article is published in Biophysical Journal.The article was published on 1999-07-01 and is currently open access. It has received 533 citations till now. The article focuses on the topics: Dielectrophoresis & Particle.
Citations
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Journal ArticleDOI
TL;DR: This critical review summarizes developments in microfluidic platforms that enable the miniaturization, integration, automation and parallelization of (bio-)chemical assays and attempts to provide a selection scheme based on key requirements of different applications and market segments.
Abstract: This critical review summarizes developments in microfluidic platforms that enable the miniaturization, integration, automation and parallelization of (bio-)chemical assays (see S. Haeberle and R. Zengerle, Lab Chip, 2007, 7, 1094–1110, for an earlier review). In contrast to isolated application-specific solutions, a microfluidic platform provides a set of fluidic unit operations, which are designed for easy combination within a well-defined fabrication technology. This allows the easy, fast, and cost-efficient implementation of different application-specific (bio-)chemical processes. In our review we focus on recent developments from the last decade (2000s). We start with a brief introduction into technical advances, major market segments and promising applications. We continue with a detailed characterization of different microfluidic platforms, comprising a short definition, the functional principle, microfluidic unit operations, application examples as well as strengths and limitations of every platform. The microfluidic platforms in focus are lateral flow tests, linear actuated devices, pressure driven laminar flow, microfluidic large scale integration, segmented flow microfluidics, centrifugal microfluidics, electrokinetics, electrowetting, surface acoustic waves, and dedicated systems for massively parallel analysis. This review concludes with the attempt to provide a selection scheme for microfluidic platforms which is based on their characteristics according to key requirements of different applications and market segments. Applied selection criteria comprise portability, costs of instrument and disposability, sample throughput, number of parameters per sample, reagent consumption, precision, diversity of microfluidic unit operations and the flexibility in programming different liquid handling protocols (295 references).

1,536 citations


Cites background from "Separation of Submicron Bioparticle..."

  • ...for the controlled separation and trapping of submicron bioparticles [245], for the fusion and transport of cells [246], or the separation of metallic from semiconducting carbon nanotubes [13, 247–249]....

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Journal ArticleDOI
TL;DR: 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.
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 separation/enrichment 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.

1,130 citations

Journal ArticleDOI
TL;DR: These kinds of platforms only that allow performance of a set of microfluidic functions which can be easily combined within a well defined and consistent fabrication technology to implement application specific biochemical assays in an easy, flexible and ideally monolithically way are reviewed.
Abstract: We review microfluidic platforms that enable the miniaturization, integration and automation of biochemical assays. Nowadays nearly an unmanageable variety of alternative approaches exists that can do this in principle. Here we focus on those kinds of platforms only that allow performance of a set of microfluidic functions—defined as microfluidic unit operations—which can be easily combined within a well defined and consistent fabrication technology to implement application specific biochemical assays in an easy, flexible and ideally monolithically way. The microfluidic platforms discussed in the following are capillary test strips, also known as lateral flow assays, the “microfluidic large scale integration” approach, centrifugal microfluidics, the electrokinetic platform, pressure driven droplet based microfluidics, electrowetting based microfluidics, SAW driven microfluidics and, last but not least, “free scalable non-contact dispensing”. The microfluidic unit operations discussed within those platforms are fluid transport, metering, mixing, switching, incubation, separation, droplet formation, droplet splitting, nL and pL dispensing, and detection.

1,068 citations

Journal ArticleDOI
TL;DR: This paper provides an extensive review of various passive and active separation techniques including basic theories and experimental details, the working principles are explained in detail, and performances of the devices are discussed.
Abstract: Separation and sorting of micron-sized particles has great importance in diagnostics, chemical and biological analyses, food and chemical processing and environmental assessment. By employing the unique characteristics of microscale flow phenomena, various techniques have been established for fast and accurate separation and sorting of microparticles in a continuous manner. The advancements in microfluidics enable sorting technologies that combine the benefits of continuous operation with small-sized scale suitable for manipulation and probing of individual particles or cells. Microfluidic sorting platforms require smaller sample volume, which has several benefits in terms of reduced cost of reagents, analysis time and less invasiveness to patients for sample extraction. Additionally, smaller size of device together with lower fabrication cost allows massive parallelization, which makes high-throughput sorting possible. Both passive and active separation and sorting techniques have been reported in literature. Passive techniques utilize the interaction between particles, flow field and the channel structure and do not require external fields. On the other hand, active techniques make use of external fields in various forms but offer better performance. This paper provides an extensive review of various passive and active separation techniques including basic theories and experimental details. The working principles are explained in detail, and performances of the devices are discussed.

613 citations

Journal ArticleDOI
TL;DR: This first application of iDEP for simultaneous live/dead bacteria separation and concentration illustrates its potential as a front-end method for bacterial analysis.
Abstract: Insulator-based (electrodeless) dielectrophoresis (iDEP) is an innovative approach in which the nonuniform electric field needed to drive DEP is produced by insulators, avoiding problems associated with the use of electrodes. Live and dead Escherichia coli were concentrated and selectively released by applying stepped DC voltages across a microchannel containing an array of insulating posts etched in glass. The only electrodes present were two platinum wires placed in the inlet and outlet reservoirs, producing mean electric fields of up to 200 V/mm across the insulators. The cells were labeled with Syto 9 and propidium iodide and imaged through a fluorescent microscope. Cell trapping and release were controlled by modifying the relative responses of electrokinesis and DEP by adjusting the magnitude of the applied voltage. Dead cells were observed to have significantly lower dielectrophoretic mobility than live cells, whereas the electrokinetic mobilities of live and dead cells were indistinguishable. The ...

477 citations

References
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Book
01 Jan 1973
TL;DR: CRC handbook of chemistry and physics, CRC Handbook of Chemistry and Physics, CRC handbook as discussed by the authors, CRC Handbook for Chemistry and Physiology, CRC Handbook for Physics,
Abstract: CRC handbook of chemistry and physics , CRC handbook of chemistry and physics , کتابخانه مرکزی دانشگاه علوم پزشکی تهران

52,268 citations

Book
02 Dec 2009
TL;DR: In this paper, a detailed account of the electromechanical interactions that govern the behaviour of small particles when an electric or magnetic field is present is presented, with numerous real-world examples.
Abstract: Small particles in the size range from one micron to one millimetre are increasingly important in today's technological world. They serve as workhorses in many mechanisms and devices - from electrostatic copiers to fluidised beds. A more recent development involves the characterisation and manipulation of individual cells and DNA molecules. Particulates can also be a hazard, for example, particulate pollution. Because all particles have electrical and magnetic properties associated with their shape and the materials of which they are constituted, they experience forces and torques when subjected to electric and/or magnetic fields. This book offers a lucid account of the electromechanical interactions that govern the behaviour of particles when an electric or magnetic field is present. With numerous real-world examples, the book should interest a wide range of scientists and engineers.

2,468 citations


"Separation of Submicron Bioparticle..." refers background in this paper

  • ...The magnitude of the dipole moment depends on the polarizability of the particle, and this in turn is governed by the dielectric properties of the particle and the medium (Pohl, 1978; Jones, 1995)....

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  • ...The time-averaged DEP force is (Jones, 1995) FDEP 5 2pr3emRe$K~v!...

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Journal ArticleDOI
TL;DR: In this article, the frequency dependency and magnitude of electrothermally induced fluid flow are discussed for low frequencies (up to 500 kHz) and the effects of Brownian motion, diffusion and buoyancy force are discussed in the context of the controlled manipulation of sub-micrometre particles.
Abstract: Ac electrokinetics is concerned with the study of the movement and behaviour of particles in suspension when they are subjected to ac electrical fields. The development of new microfabricated electrode structures has meant that particles down to the size of macromolecules have been manipulated, but on this scale forces other than electrokinetic affect particles behaviour. The high electrical fields, which are required to produce sufficient force to move a particle, result in heat dissipation in the medium. This in turn produces thermal gradients, which may give rise to fluid motion through buoyancy, and electrothermal forces. In this paper, the frequency dependency and magnitude of electrothermally induced fluid flow are discussed. A new type of fluid flow is identified for low frequencies (up to 500 kHz). Our preliminary observations indicate that it has its origin in the action of a tangential electrical field on the diffuse double layer of the microfabricated electrodes. The effects of Brownian motion, diffusion and the buoyancy force are discussed in the context of the controlled manipulation of sub-micrometre particles. The orders of magnitude of the various forces experienced by a sub-micrometre latex particle in a model electrode structure are calculated. The results are compared with experiment and the relative influence of each type of force on the overall behaviour of particles is described.

1,184 citations


"Separation of Submicron Bioparticle..." refers background or methods in this paper

  • ...Generally at field strengths in the range of 10 5 to 10(6) Vm(21), our observations indicate that although these forces are present and give rise to fluid motion, the influence is less than the dielectrophoretic force acting on the particles (Ramos et al., 1998)....

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  • ...Thermal equilibrium is achieved rapidly, within 1 ms of application of the electric field (Ramos et al., 1998), and both calculations and measurements show that for low conductivity media the steady-state temperature rise is small and not sufficient to denature biological samples....

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  • ...Generally at field strengths in the range of 105 to 106 Vm21, our observations indicate that although these forces are present and give rise to fluid motion, the influence is less than the dielectrophoretic force acting on the particles (Ramos et al., 1998)....

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  • ...Although natural convection is negligible (Ramos et al., 1998), the high electric field gives rise to volume forces on the liquid (the electrothermal force)....

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  • ...As an example, it has been shown that for the simple case of an interdigitated electrode geometry in contact with a medium of conductivity 0.01 Sm21 (with 20 V peak to peak applied), the steady-state temperature rise can be calculated to be 6°C (Ramos et al., 1998)....

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Journal ArticleDOI
TL;DR: In this article, it was shown that the phenomena of dielectrophoresis and dielectro-precipitation can be observed under rather ideal conditions, though it is ordinarily often difficult to do so because of the presence of the more easily produced electrophoreis or ion-type migration of charged particles.
Abstract: The motion of suspensoid particles relative to that of the solvent resulting from polarization forces produced by an inhomogeneous electric field is defined as ``dielectrophoresis.'' It is analogous to the related phenomenon of electrophoresis, in which motion of suspensoid particles is produced by the action of an electrostatic field on the charged particles.From a consideration of theoretical calculations and from experimental observations it is concluded that the phenomena of ``dielectrophoresis'' and ``dielectro‐precipitation'' can be observed under rather ideal conditions, though it is ordinarily often difficult to do so because of the presence of the more easily produced electrophoresis or ion‐type migration of charged particles.The usefulness of dielectrophoresis (and/or electrophoresis) for removing suspended solid particles from polymer solutions during analysis is described.

1,023 citations


"Separation of Submicron Bioparticle..." refers background in this paper

  • ...This force was termed dielectrophoresis (DEP) by Pohl (1951, 1978)....

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Journal ArticleDOI
TL;DR: Findings indicate that the dielectric affinity technique may prove useful in a wide variety of cell separation and characterization applications.
Abstract: Electrorotation measurements were used to demonstrate that the dielectric properties of the metastatic human breast cancer cell line MDA231 were significantly different from those of erythrocytes and T lymphocytes. These dielectric differences were exploited to separate the cancer cells from normal blood cells by appropriately balancing the hydrodynamic and dielectrophoretic forces acting on the cells within a dielectric affinity column containing a microelectrode array. The operational criteria for successful particle separation in such a column are analyzed and our findings indicate that the dielectric affinity technique may prove useful in a wide variety of cell separation and characterization applications.

715 citations


"Separation of Submicron Bioparticle..." refers background in this paper

  • ..., 1994), breast cancer cells (Becker et al., 1995), and CD34 1 cells (Stephens et al....

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  • ...It has also been demonstrated that leukemic cells (Becker et al., 1994), breast cancer cells (Becker et al., 1995), and CD341 cells (Stephens et al., 1996) can be separated or enriched from human blood....

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