Focusing and continuous separation of cells in a microfluidic device using lateral dielectrophoresis

Demierre, Nicolas; Braschler, Thomas; Müller, Randoald; Renaud, Philippe

doi:10.1016/j.snb.2007.09.078

Cited by 115 publications

(79 citation statements)

References 17 publications

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“…Angled electrodes are employed in an integrated DEP chip design for the continuous filtering and sorting of bioparticles, 109 and also used to great effect in a continuous DEP size-based particle sorter 110 and a multitarget DEP activated cell sorter described by Kim et al 111 A simple arrangement for aligning cells in fluidic channels, consisting of two face-to-face strip electrodes mounted on the top and bottom of a microchannel, has been described by Schnelle et al 112 In this device, particles exhibiting negative DEP are brought by fluid flow to an energized electrode pair, and as a result of experiencing repulsion forces from both electrodes are lifted into the central stream of the fluid flow. This basic concept has been refined by Demierre et al 113 who fabricated a microfluidic device based on an arrangement of lateral metal electrodes and a patterned insulator. This device combines the concept of insulator-based "electrodeless" DEP with multiple frequencies to achieve focusing and continuous separation of dielectric particles flowing through a channel.…”

Section: Technologymentioning

confidence: 99%

Review Article—Dielectrophoresis: Status of the theory, technology, and applications

2010

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A review is presented of the present status of the theory, the developed technology and the current applications of dielectrophoresis ͑DEP͒. 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 resist͒ and methods for fabricating the electrodes and microfluidics of DEP devices ͑photo and electron beam lithography, laser ablation, thin film techniques, CMOS technology͒. 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 components͒. 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 nanoparticles͒ 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.

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Section: Technologymentioning

confidence: 99%

Review Article—Dielectrophoresis: Status of the theory, technology, and applications

2010

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“…Cell focusing using negativeDEP, controlling the distance the cells are repelled from the electrode surfaces, can also be used instead of trapping to implement cell sorting in the original sample. [58][59][60][61] However, this approach may not provide enough selectivity as all cells would likely be focused to the same stream in such high electrical conductivity media and re-suspension or dilution may still be necessary. In any case, a computational model to obtain the net force field and potential particle trajectories will be crucial to allow for the design of carbonDEP devices with an expected functionality.…”

Section: Discussionmentioning

confidence: 99%

Enrichment of diluted cell populations from large sample volumes using 3D carbon-electrode dielectrophoresis

et al. 2016

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Here, we report on an enrichment protocol using carbon electrode dielectrophoresis to isolate and purify a targeted cell population from sample volumes up to 4 ml. We aim at trapping, washing, and recovering an enriched cell fraction that will facilitate downstream analysis. We used an increasingly diluted sample of yeast, 10 6 -10 2 cells/ml, to demonstrate the isolation and enrichment of few cells at increasing flow rates. A maximum average enrichment of 154.2 6 23.7 times was achieved when the sample flow rate was 10 ll/min and yeast cells were suspended in low electrically conductive media that maximizes dielectrophoresis trapping. A COMSOL Multiphysics model allowed for the comparison between experimental and simulation results. Discussion is conducted on the discrepancies between such results and how the model can be further improved. Published by AIP Publishing.

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“…8,9 Briefly, liquid electrodes are planar electrodes fabricated on the bottom of dead-end chambers on the side of the main channel. The insulator guides the field lines in the liquid flowing into the main channel and determines the electric field distribution inside the microstructure.…”

Section: Microfluidic Chip Design and The Working Principlementioning

confidence: 99%

An impedance-based flow microcytometer for single cell morphology discrimination

et al. 2014

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Cell shape is a fundamental biological feature, providing specific information about physiological or pathological cellular conditions. Most of the state-of-the-art microfluidic cytometers, however, only allow simple cell analysis, including viability studies, cell counting and sorting. In this work, we present a non-invasive, label-free device capable of single cell morphology discrimination in continuous flow. The device is based on the principle of liquid electrodes, fabricated in a cross configuration around a sensing zone. This arrangement allows measurement of cell impedance along orthogonal orientations and extraction of an index describing cell shape anisotropy. By adding prior to the sensing volume a series of lateral liquid electrodes, the particle stream was focused toward the channel midline and each cell was oriented in a specific direction before shape sensing. We demonstrate the proof of concept by performing spherical and elongated particle discrimination. As an application, we show that the shape changes experienced during cell division can be monitored and characterized. In particular, budding yeasts at different stages of the mitotic cycle were identified by extracting their anisotropy index.

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Focusing and continuous separation of cells in a microfluidic device using lateral dielectrophoresis

Cited by 115 publications

References 17 publications

Review Article—Dielectrophoresis: Status of the theory, technology, and applications

Review Article—Dielectrophoresis: Status of the theory, technology, and applications

Enrichment of diluted cell populations from large sample volumes using 3D carbon-electrode dielectrophoresis

An impedance-based flow microcytometer for single cell morphology discrimination

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