Cell immersion and cell dipping in microfluidic devicesElectronic supplementary information (ESI) available: cell dipping video sequence from which Fig. 7 was extracted and cell dipping video sequence with close-ups. See http://www.rsc.org/suppdata/lc/b3/b311210a/

Seger, Urban; Gawad, Shady; Johann, Robert; Bertsch, Arnaud; Renaud, Philippe

doi:10.1039/b311210a

Cited by 82 publications

(45 citation statements)

References 22 publications

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“…An alternative potential mechanism for separation is dielectrophoresis (DEP), the translational motion of charge-neutral matter caused by polarization effects in nonuniform electric fields (15). Because of the relatively facile engineering of the electric fields and interface to integrated electronics, DEP provides an especially attractive force field for on-chip cell manipulation (16,17).The time-averaged dielectrophoretic force on a homogeneous sphere of radius r p , ignoring higher order effects of polarization, can be approximated as (18)where E rms is the electric field strength, m is the permittivity of the suspending medium, is the angular frequency, and Re( f CM ()) is the real part of the dipolar Clausius-Mossotti (CM) factor. The CM factor is bound by the limits Ϫ0.5 Ͻ Re( f CM ()) Ͻ 1 and describes the relative polarization of the particle versus that of the surrounding medium given by f CM () ϭ (* p () Ϫ * m ())͞(* p () ϩ 2* m ()), where * p and * m are the complex permittivities of the particle and medium, respectively.…”

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Marker-specific sorting of rare cells using dielectrophoresis

Bessette²,

Qian³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

408

299

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Current techniques in high-speed cell sorting are limited by the inherent coupling among three competing parameters of performance: throughput, purity, and rare cell recovery. Microfluidics provides an alternate strategy to decouple these parameters through the use of arrayed devices that operate in parallel. To efficiently isolate rare cells from complex mixtures, an electrokinetic sorting methodology was developed that exploits dielectrophoresis (DEP) in microfluidic channels. In this approach, the dielectrophoretic amplitude response of rare target cells is modulated by labeling cells with particles that differ in polarization response. Cell mixtures were interrogated in the DEP-activated cell sorter in a continuous-flow manner, wherein the electric fields were engineered to achieve efficient separation between the dielectrophoretically labeled and unlabeled cells. To demonstrate the efficiency of marker-specific cell separation, DEP-activated cell sorting (DACS) was applied for affinity-based enrichment of rare bacteria expressing a specific surface marker from an excess of nontarget bacteria that do not express this marker. Rare target cells were enriched by >200-fold in a single round of sorting at a single-channel throughput of 10,000 cells per second. DACS offers the potential for automated, surface marker-specific cell sorting in a disposable format that is capable of simultaneously achieving high throughput, purity, and rare cell recovery.cell sorting ͉ microfluidics C ell sorters are capable of separating a heterogeneous suspension of particles into purified fractions and thus have become an indispensable tool in biology and medicine. Emerging applications of cell sorting technology span a broad spectrum of pharmaceutical and biomedical fields that range from cancer diagnostics to cell-based therapies (1-3). The most widely used methodologies for cell separation are magnetic-activated cell sorting (MACS) and fluorescence-activated cell sorting (FACS). MACS is a selection technique that is capable of capturing a large number of target cells in parallel (4); however, the purity and recovery in MACS typically have large variances (5). In contrast, FACS relies upon serially screening each cell, yielding high performance in cell recovery and purity (6). However, because of the serial nature of its operation, FACS allows for a comparatively low throughput, typically in the range between 10 4 and 10 5 cells per second (7). Regardless of the mechanism, the performance of cell separation is typically characterized by three metrics. ''Throughput'' gauges how many cell characterization and sorting operations can be executed per unit of time, ''purity'' is the fraction of the target cells in the collection vessel, and ''recovery'' is the fraction of the input target cells successfully sorted into the collection vessel. Demands placed on cell sorting technologies continue to increase, because cell sorting applications are expanding and biological questions are becoming more complex (7). For example, rare cell sort...

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Marker-specific sorting of rare cells using dielectrophoresis

Bessette²,

Qian³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

408

299

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“…Both FE and SE use the angled DEP electrode geometry, which has been previously implemented by a number of groups including ours (24)(25)(26)(27). In this scheme, the electrodes operate in the negative DEP regime where the cells are physically repelled from areas of higher electric field gradients (i.e., near the electrode edges) into weaker field regions.…”

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confidence: 99%

Selection of mammalian cells based on their cell-cycle phase using dielectrophoresis

Kim

Shu²,

Dane³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

136

120

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An effective, noninvasive means of selecting cells based on their phase within the cell cycle is an important capability for biological research. Current methods of producing synchronous cell populations, however, tend to disrupt the natural physiology of the cell or suffer from low synchronization yields. In this work, we report a microfluidic device that utilizes the dielectrophoresis phenomenon to synchronize cells by exploiting the relationship between the cell's volume and its phase in the cell cycle. The dielectrophoresis activated cell synchronizer (DACSync) device accepts an asynchronous mixture of cells at the inlet, fractionates the cell populations according to the cell-cycle phase (G 1/S and G2/M), and elutes them through different outlets. The device is gentle and efficient; it utilizes electric fields that are 1-2 orders of magnitude below those used in electroporation and enriches asynchronous tumor cells in the G 1 phase to 96% in one round of sorting, in a continuous flow manner at a throughput of 2 ؋ 10 5 cells per hour per microchannel. This work illustrates the feasibility of using laminar flow and electrokinetic forces for the efficient, noninvasive separation of living cells.cell synchronization ͉ microfluidics ͉ cell sorting ͉ electrokinetics T he cell cycle is comprised of a series of carefully coordinated cellular events encompassing the cell growth, the duplication of DNA, and the formation of daughter cells (1-3). Gentle and effective methods for synchronizing cells at a particular phase within the cell cycle are of significant biotechnological utility. For example, many anticancer drugs target cells in a particular phase [e.g., Paclitaxel targets the M phase by inhibiting microtubule disassembly (4), and Methotrexate targets the S phase by inhibiting dihydrofolate reductase (5)]; therefore, achieving effective synchrony of the tumor cell samples is critical to understanding their behavior and their response to chemotherapeutics.Currently, there are two prevalent methods for achieving cell synchrony. The more widely used is the cell arrest and release technique (6), in which metabolic agents are used to arrest cells at a particular phase, allow other cells to accumulate at that phase, and then release them in synchrony by using a second chemical agent. Unfortunately, however, although this technique yields relatively high levels of synchrony, it has the undesirable effect of disturbing the normal physiology of the cell. In severe cases, the metabolic agents induce apoptosis (7,8). The centrifugal elutriation technique (9) separates cells by injecting them into an elutriation rotor spinning at a constant g-force. When the centrifugal force is balanced with the opposing force from the flow rate, cells float and elute at specific positions. Although this method has some advantages over the cell arrest and release technique, it typically involves complex, time-consuming preparations and imposes significant mechanical stress on the cells (10). It thus appears that there is a need for facile...

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“…Angled electrode structures have also been used as "funnels" to guide particle motion within a channel or as part of the function of a microsystem [55][56][57][58][59]. As DEP separators, angled electrode structures have been found favorable in their reliance on negative DEP for inducing forces of different strength on particles of different properties.…”

Section: Dielectrophoretic Separation Using Angled Electrodesmentioning

confidence: 99%

Continuous separation of colloidal particles using dielectrophoresis

2013

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Continuous separation of colloidal particles using dielectrophoresisDielectrophoresis is the movement of particles in nonuniform electric fields and has been of interest for application to manipulation and separation at and below the microscale. This technique has the advantages of being noninvasive, nondestructive, and noncontact, with the movement of particle achieved by means of electric fields generated by miniaturized electrodes and microfluidic systems. Although the majority of applications have been above the microscale, there is increasing interest in application to colloidal particles around a micron and smaller. This paper begins with a review of colloidal and nanoscale dielectrophoresis with specific attention paid to separation applications. An innovative design of integrated microelectrode array and its application to flow-through, continuous separation of colloidal particles is then presented. The details of the angled chevron microelectrode array and the test microfluidic system are then discussed. The variation in device operation with applied signal voltage is presented and discussed in terms of separation efficiency, demonstrating 99.9% separation of a mixture of colloidal latex spheres. Keywords:Colloidal / Dielectrophoresis / Separation DOI 10.1002/elps.2012004661 Introduction GeneralDielectrophoresis (DEP) is the motion arising from the interaction of nonuniform electric fields and the induced electrical dipole in polarizable particles [1][2][3][4][5]. The standard electrical technique of electrophoretic separation works when suspended charged particles migrate under the influence of applied electric field. DEP has distinct advantages over this technique in that it can separate neutral particles as well, allowing the separation of particles without having to physiologically alter them; which gives minimum particle handling and no damage. DEP also typically uses microfabricated electrodes to generate highly nonuniform electric fields, which allows it to be performed locally, whereas electrophoretic separation is generally a long-range effect acting between two large external electrodes. Due to the requirements for microfabrication, the localized nature of DEP, and the rapid growth of microfluidic Labon-a-Chip systems or TAS in the past two decades in both research and commercial sectors [6][7][8], there has been a recent growth in the application of DEP to these areas. The first practical application of Lab-on-a-Chip was in fact on-chip CE [9] and with recent advances in the synthesis and the charCorrespondence: Dr. Nicolas Green, Nano Group, School of Electronics and Computer Science, University of Southampton, Highfield, Southampton, SO17 1BJ, UK E-mail: ng2@ecs.soton.ac.uk Fax: +44-2380593029 acterization of size-selected particles in the submicron and nanometer (colloidal) range, an investigation of their physical and chemical properties is now possible [10]. The capability to produce small scale devices allows the development of entirely novel experiments and chip-based analytical system...

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Cell immersion and cell dipping in microfluidic devicesElectronic supplementary information (ESI) available: cell dipping video sequence from which Fig. 7 was extracted and cell dipping video sequence with close-ups. See http://www.rsc.org/suppdata/lc/b3/b311210a/

Cited by 82 publications

References 22 publications

Marker-specific sorting of rare cells using dielectrophoresis

Marker-specific sorting of rare cells using dielectrophoresis

Selection of mammalian cells based on their cell-cycle phase using dielectrophoresis

Continuous separation of colloidal particles using dielectrophoresis

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