Enhanced contactless dielectrophoresis enrichment and isolation platform via cell-scale microstructures

Čemažar, Jaka; Douglas, Temple A.; Schmelz, Eva M.; Davalos, Rafael V.

doi:10.1063/1.4939947

Cited by 46 publications

(58 citation statements)

References 52 publications

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“…In previous studies, we have shown that because the DEP force is dependent on the gradient of the electric field squared rather than its magnitude, using 20‐μm posts in the device improves separation specificity by reducing cell clumping and pearl chaining, a process involving a strand of cells forming in response to the DEP force. Cell‐size posts also maintain high viability in the output population by maximizing the ratio

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while still being large enough to trap cells . By limiting to single or two cell trapping, as shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

A feasibility study for enrichment of highly aggressive cancer subpopulations by their biophysical properties via dielectrophoresis enhanced with synergistic fluid flow

et al. 2017

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A common problem with cancer treatment is the development of treatment resistance and tumor recurrence that result from treatments that kill most tumor cells yet leave behind aggressive cells to repopulate. Presented here is a microfluidic device that can be used to isolate tumor subpopulations to optimize treatment selection. Dielectrophoresis (DEP) is a phenomenon where particles are polarized by an electric field and move along the electric field gradient. Different cell subpopulations have different DEP responses depending on their bioelectrical phenotype, which, we hypothesize, correlate with aggressiveness. We have designed a microfluidic device in which a region containing posts locally distorts channel of the electric field created by an AC voltage across a microfluidic channel and which forces cells toward the posts through DEP. This force is balanced with a simultaneous drag force from fluid motion that pulls cells away from the posts. We have shown that by adjusting the drag force, cells with aggressive phenotypes are influenced more by the DEP force and trap on posts while others flow through the chip unaffected. Utilizing single-cell trapping on cell-sized posts by a drag-DEP force balance, we show that separation of very similar cell subpopulations may be achieved, a result that was previously impossible with DEP alone. Separated subpopulations maintain high viability downstream, and remain in a native state, without fluorescent labeling. These cells can then be cultured to help select a therapy that kills aggressive subpopulations equally or better than the bulk of the tumor, mitigating resistance and recurrence.

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\nabla | \vec{boldE} {false|}^{2} / false| \vec{boldE} false|

while still being large enough to trap cells . By limiting to single or two cell trapping, as shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

A feasibility study for enrichment of highly aggressive cancer subpopulations by their biophysical properties via dielectrophoresis enhanced with synergistic fluid flow

et al. 2017

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“…This study successfully demonstrates a unique form of implementing cDEP, [143]. In [143], the device had a channel depth of 50 μm with microfluidic structures composed of PDMS at a 10:1 ratio.…”

Section: Discussionmentioning

confidence: 99%

“…In [143], the device had a channel depth of 50 μm with microfluidic structures composed of PDMS at a 10:1 ratio. The barrier between the liquid electrodes and sample channel was made of PDMS with a 5:1 ratio 13 μm thick.…”

Section: Discussionmentioning

confidence: 99%

The use of microfluidics and dielectrophoresis for separation, concentration, and identification of bacteria

et al. 2016

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Traditional bacterial analyses take one to two days under favorable conditions where the bulk of the time is spent waiting for bacteria to divide and grow until visual colonies can be observed for identification. In the case of bacteria with slow doubling times, this process can take weeks. This delay in analysis is unacceptable, especially in cases of life threatening diseases or emergencies. It is clear that in order to decrease the analysis time of the bacteria, the culturing and growth step must be circumvented. The goal of this research is to design, build, and test a device that could decrease the analysis time of bacteria using label-free methods of dielectrophoresis and Raman spectroscopy.Testing for device design was performed with clinical samples in mind, which consist of bacteria grown in a variety of environmental conditions (i.e. available food sources, growth stage, temperature, etc.) and accompanied by sample debris. Raman spectra of bacteria grown in varying media and metabolic stages were collected and analyzed. Results indicate that growth phase and media have an impact on Raman spectra iv and is distinguishable by linear discriminant analysis (LDA). Despite these spectral differences, it was found that LDA classification of closely related bacteria remains fairly high (90%) regardless of growth phase. Sample debris were also considered in device design and accommodated for by dielectrophoresis. Devices were built with the goal to isolate bacteria from a mixed sample and simultaneously acquire Raman spectra for identification.For this dissertation, a device was designed, built, and tested that incorporates dielectrophoresis for particle isolation and Raman spectroscopy for identification. The device was modeled in COMSOL to ensure that an appropriate electrical field gradient could be obtained to isolate bacteria from 5 µm diameter polystyrene spheres. The device was built and successfully trapped bacteria away from polystyrene spheres and Raman spectra of the bacteria were collected while trapped. These results indicate a clear potential for contactless dielectrophoresis-Raman devices to isolate and identify bacteria from sample debris, and thereby decrease the analysis time of bacteria. Typical bacterial analysis involves culturing and visualizing colonies on an array of agar plates. The growth patterns and colors among the array are used to identify the bacteria. For fast growing bacteria such as Escherichia coli, analysis will take one to two days. However, slow growing bacteria such as mycobacteria can take weeks to identify.In addition, there are some species of bacteria that are viable but nonculturable. This lengthy analysis time is unacceptable for life-threatening infections and emergency situations. It is clear that to decrease the analysis of the bacteria, the culturing and growth steps must be avoided. The goal of this research is to design, build, and test a device that could decrease the analysis time of bacteria.

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“…Microbiological samples can be DEP manipulated using different approaches like free flow fractionation, separation in a traveling wave, capture on isolated structures, contactless and barrier dielectrophoresis .…”

Section: Introductionmentioning

confidence: 99%

Barrier contactless dielectrophoresis: A new approach to particle separation

Podoynitsyn

Sorokina

Klimov

et al. 2019

Separation Science Plus

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Barrier contactless dielectrophoresis is proposed as a method for microbiological particle separation. Design of a separation device for barrier contactless dielectrophoresis is discussed. The principle of separation device is based on formation of barriers of gradient fields in the volume of separation chamber by electrodes with passivation dielectric coating of silicon carbide. A feature of the method is absence of contact between separated samples and conductive elements of electrode structure. The proposed method is highly efficient and easy to use in comparison with dielectrophoresis on isolated structures and conventional planar systems. Computer simulation of electric field distribution over dielectrophoretic barriers is carried out, and effect of the thickness of the passivation coating on dielectrophoretic properties of barriers is shown. Forces acting on a particle (a yeast cell with a diameter of 7 μm) in separation chamber are evaluated using computer simulation data. Ability of the cell to be captured by the method of contactless barrier dielectrophoresis is theoretically predicted and confirmed experimentally, using yeast cells. The yeast cells subjected to positive dielectrophoresis can be effectively captured (up to 90%) by the separation device at the applied voltage of 20 V and 100 kHz and at flow rate of 20 mL/h.

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Enhanced contactless dielectrophoresis enrichment and isolation platform via cell-scale microstructures

Cited by 46 publications

References 52 publications

A feasibility study for enrichment of highly aggressive cancer subpopulations by their biophysical properties via dielectrophoresis enhanced with synergistic fluid flow

A feasibility study for enrichment of highly aggressive cancer subpopulations by their biophysical properties via dielectrophoresis enhanced with synergistic fluid flow

The use of microfluidics and dielectrophoresis for separation, concentration, and identification of bacteria

Barrier contactless dielectrophoresis: A new approach to particle separation

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