Modeling and development of a low frequency contactless dielectrophoresis (cDEP) platform to sort cancer cells from dilute whole blood samples

Sano, Michael B.; Caldwell, John L.; Davalos, Rafael V.

doi:10.1016/j.bios.2011.07.048

Cited by 83 publications

(39 citation statements)

References 35 publications

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“…38 cDEP has been used to isolate tumor initiating cells (TICs) from non-initiating cells 38 and to separate living cancer cells from dead cells 37 and from red blood cells. 39 It has also been shown recently with cDEP that breast cancer cells from different cell lines exhibit unique dielectrophoretic responses and highly metastatic cell lines can be isolated from less metastatic lines. 40 In this work, we examined the changes in dielectrophoretic response of MOSE cells as they progress from benign to aggressive stages of ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

Dielectrophoretic differentiation of mouse ovarian surface epithelial cells, macrophages, and fibroblasts using contactless dielectrophoresis

et al. 2012

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Ovarian cancer is the leading cause of death from gynecological malignancies in women. The primary challenge is the detection of the cancer at an early stage, since this drastically increases the survival rate. In this study we investigated the dielectrophoretic responses of progressive stages of mouse ovarian surface epithelial (MOSE) cells, as well as mouse fibroblast and macrophage cell lines, utilizing contactless dielectrophoresis (cDEP). cDEP is a relatively new cell manipulation technique that has addressed some of the challenges of conventional dielectrophoretic methods. To evaluate our microfluidic device performance, we computationally studied the effects of altering various geometrical parameters, such as the size and arrangement of insulating structures, on dielectrophoretic and drag forces. We found that the trapping voltage of MOSE cells increases as the cells progress from a nontumorigenic, benign cell to a tumorigenic, malignant phenotype. Additionally, all MOSE cells display unique behavior compared to fibroblasts and macrophages, representing normal and inflammatory cells found in the peritoneal fluid. Based on these findings, we predict that cDEP can be utilized for isolation of ovarian cancer cells from peritoneal fluid as an early cancer detection tool. V C 2012 American Institute of Physics. [http://dx

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Section: Introductionmentioning

confidence: 99%

Dielectrophoretic differentiation of mouse ovarian surface epithelial cells, macrophages, and fibroblasts using contactless dielectrophoresis

et al. 2012

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“…With the aid of a step-up transformer or other equipment modifications as suggested in [152], higher voltages can be obtained without approaching the dielectric breakdown of fused silica (950 V/μm [153]) while maintaining a range of optimal and commonly used frequencies (1-1000 kHz [147]). Future work will make use of such equipment to demonstrate how fused silica can provide a higher range of applied voltage due to the dielectric breakdown.…”

Section: Discussionmentioning

confidence: 99%

“…Sano et al [147] Future work will address issues raised from the current design. For example, the flow rate used for this study was the same or slower than other research articles, as listed in Table 5.1.…”

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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“…The presented technique has been successfully used for a variety of more complex and physiologically relevant applications, including sorting live and dead cells, 28 tumor initiating cells from prostate cancer cells, 30 cancer cells from dilute red blood cells, 31,32 and differentiating among stages of breast cancer 37 and ovarian cancer. 29 cDEP has also been used for mixing particles.…”

Section: 36mentioning

confidence: 99%

“…[28][29][30][31] Lower frequency (5-100 kHz) devices operate continuously, and when operated at a frequency at which one population experiences pDEP while the background population experiences nDEP, can redirect particle trajectories to achieve sorting. [32][33][34] These low frequency devices have been used to sort cancer cells from red blood cells, determine the changes in dielectric properties of a progressive MOSE cell line, and to elucidate the effects of non-toxic sphingolipid treatments on reversing aggressive characteristics of aggressive MOSE cells. Additionally, cDEP microdevices can be designed to operate at increased throughput, currently up to 1 ml/hr.…”

Section: Introductionmentioning

confidence: 99%

Label-free Isolation and Enrichment of Cells Through Contactless Dielectrophoresis

Elvington

Salmanzadeh

Stremler

et al. 2013

JoVE

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Dielectrophoresis (DEP) is the phenomenon by which polarized particles in a non-uniform electric field undergo translational motion, and can be used to direct the motion of microparticles in a surface marker-independent manner. Traditionally, DEP devices include planar metallic electrodes patterned in the sample channel. This approach can be expensive and requires a specialized cleanroom environment. Recently, a contact-free approach called contactless dielectrophoresis (cDEP) has been developed. This method utilizes the classic principle of DEP while avoiding direct contact between electrodes and sample by patterning fluidic electrodes and a sample channel from a single polydimethylsiloxane (PDMS) substrate, and has application as a rapid microfluidic strategy designed to sort and enrich microparticles. Unique to this method is that the electric field is generated via fluidic electrode channels containing a highly conductive fluid, which are separated from the sample channel by a thin insulating barrier. Because metal electrodes do not directly contact the sample, electrolysis, electrode delamination, and sample contamination are avoided. Additionally, this enables an inexpensive and simple fabrication process. cDEP is thus well-suited for manipulating sensitive biological particles. The dielectrophoretic force acting upon the particles depends not only upon spatial gradients of the electric field generated by customizable design of the device geometry, but the intrinsic biophysical properties of the cell. As such, cDEP is a label-free technique that avoids depending upon surface-expressed molecular biomarkers that may be variably expressed within a population, while still allowing characterization, enrichment, and sorting of bioparticles.Here, we demonstrate the basics of fabrication and experimentation using cDEP. We explain the simple preparation of a cDEP chip using soft lithography techniques. We discuss the experimental procedure for characterizing crossover frequency of a particle or cell, the frequency at which the dielectrophoretic force is zero. Finally, we demonstrate the use of this technique for sorting a mixture of ovarian cancer cells and fluorescing microspheres (beads).

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Modeling and development of a low frequency contactless dielectrophoresis (cDEP) platform to sort cancer cells from dilute whole blood samples

Cited by 83 publications

References 35 publications

Dielectrophoretic differentiation of mouse ovarian surface epithelial cells, macrophages, and fibroblasts using contactless dielectrophoresis

Dielectrophoretic differentiation of mouse ovarian surface epithelial cells, macrophages, and fibroblasts using contactless dielectrophoresis

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

Label-free Isolation and Enrichment of Cells Through Contactless Dielectrophoresis

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