Dielectrophoretic separation of colorectal cancer cells

Yang, Fang; Yang, Xiaoming; Hong, Jiasheng; Bulkhaults, Phillip; Wood, Patricia A.; Hrushesky, William J. M.; Wang, Guiren

doi:10.1063/1.3279786

Cited by 98 publications

(77 citation statements)

References 46 publications

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“…The throughput of the ApoStream device is faster as compared to other small microfluidic chip based DEP technologies. 19,22,32,45 A study by Hu et al showed a higher throughput of 10 000 cells per second, which is almost the twice the throughput of ApoStream device. However, that technology was limited to cell labeling.…”

Section: F Cell Viability Studiesmentioning

confidence: 98%

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ApoStream™, a new dielectrophoretic device for antibody independent isolation and recovery of viable cancer cells from blood

et al. 2012

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Isolation and enumeration of circulating tumor cells (CTCs) are used to monitor metastatic disease progression and guide cancer therapy. However, currently available technologies are limited to cells expressing specific cell surface markers, such as epithelial cell adhesion molecule (EpCAM) or have limited specificity because they are based on cell size alone. We developed a device, ApoStream TM that overcomes these limitations by exploiting differences in the biophysical characteristics between cancer cells and normal, healthy blood cells to capture CTCs using dielectrophoretic technology in a microfluidic flow chamber. Further, the system overcomes throughput limitations by operating in continuous mode for efficient isolation and enrichment of CTCs from blood. The performance of the device was optimized using a design of experiment approach for key operating parameters such as frequency, voltage and flow rates, and buffer formulations. Cell spiking studies were conducted using SKOV3 or MDA-MB-231 cell lines that have a high and low expression level of EpCAM, respectively, to demonstrate linearity and precision of recovery independent of EpCAM receptor levels. The average recovery of SKOV3 and MDA-MB-231 cancer cells spiked into approximately 12 Â 10 6 peripheral blood mononuclear cells obtained from 7.5 ml normal human donor blood was 75.4% 6 3.1% (n ¼ 12) and 71.2% 6 1.6% (n ¼ 6), respectively. The intra-day and inter-day precision coefficients of variation of the device were both less than 3%. Linear regression analysis yielded a correlation coefficient (R

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Section: F Cell Viability Studiesmentioning

confidence: 98%

“…For example, DEP has been used to separate colorectal cancer cell lines in a microfluidic chip. 22 Contactless DEP microfluidic device was utilized to study the behavior of mouse ovarian cells. 23 Human cervical carcinoma cell line HeLa was concentrated using circular microelectrodes.…”

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confidence: 99%

ApoStream™, a new dielectrophoretic device for antibody independent isolation and recovery of viable cancer cells from blood

et al. 2012

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“…DEP testing can be used to measure these properties, allowing it to be used as a characterisation tool DEP was first used on living cells by Pohl and Hawk in 1966 16 , but has since been used to both characterise and separate different populations of cells, for a variety of different purposes within biology and medicine, such as to study links between multidrug resistance and cancer, and to study apoptosis 17 . DEP has been employed in a micro-fluidic chip to separate colorectal cancer cells from E.coli bacteria and Human Embryonic Kidney 293 cells 18 . Dielectric methods have also been used to separate breast cancer cells from blood 19 , and to distinguish stem cells from their progeny 20 .…”

Section: Introductionmentioning

confidence: 99%

Human oral cancer cells with increasing tumorigenic abilities exhibit higher effective membrane capacitance

et al. 2014

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Objective: Although cells with tumorigenic / stem cell-like properties have been identified in many cancers, including oral squamous cell carcinoma (OSCC), their isolation and characterisation is still at early stages. The aim of this study was to characterise the electrophysiological properties of OSCC cells with different tumorigenic properties in order to establish if a correlation exists between tumorigenicity and electrical characteristics. Materials and Methods: Rapid adherence to collagen IV was used as a non-invasive, functional method to isolate subsets of cells with different tumorigenic abilities from one oral dysplastic and three OSCC-derived cell lines. The cell subsets identified and isolated by this method were further investigated independently using dielectrophoresis, a label-free method to determine their electrophysiological parameters. Cell membrane morphology was investigated using scanning electron microscopy (SEM) and modulated by use of 4-methylumbelliferone (4-MU). Results: The rapid adherent cells (RAC) to collagen IV, enriched for cells with increased tumorigenic ability, had significantly higher effective membrane capacitance than middle (MAC) and late (LAC) adherent cells. SEM showed that, in contrast to MAC and LAC, RAC displayed a rough surface, extremely rich in cellular protrusions. Treatment with 4-MU dramatically altered RAC cell membrane morphology by causing loss of filopodia, and decreased significantly their membrane capacitance, indicating that the highest membrane capacitance found in RAC was due to their particular cell membrane morphology. Conclusion: This is the first study showing that OSCC cells with higher tumour formation ability exhibit higher effective membrane capacitance than cells that are less tumorigenic. OSSC cells with different tumorigenic ability possessed different electrophysiological properties mostly due to their differences in the cell membrane morphology. The results suggest that dielectrophoresis may potentially be of use in the future for reliable, label-free isolation of putative tumorigenic cells.

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“…To date, DEP has been used in blood analysis, 7 including characterization of human red blood cells based on the blood type, 8 sorting and concentrating the target microbe from a flowing blood sample, 9 and isolation of red blood cells affected by malaria. 10 By exploiting subtle differences between the healthy cells and their malignant counterparts, DEP can be employed to successfully isolate different cancerous cells 11 and separate them from healthy ones, 12 identify different types of cultured tumor cells, 13 quantify electric properties of drug-resistant breast cancer cells, 14 or study key stages in apoptosis of 1932-1058/2012/6(2)/024117/15/$30.00 V C 2012 American Institute of Physics 6, 024117-1 leukemia cells. 15 Close connection between electrical properties of biological cells and their physiological and metabolic properties is often exploited to separate viable from non-viable cells, 16,17 but it also makes DEP a useful tool in studying stem cells, [18][19][20] sorting out multiple different species of bacteria [21][22][23] and subpopulations within the same bacterial species, 24 or in characterizing plant protoplasts, yeast and algae.…”

Section: Introductionmentioning

confidence: 99%

Electronic detection of dielectrophoretic forces exerted on particles flowing over interdigitated electrodes

et al. 2012

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Dielectric particles flowing through a microfluidic channel over a set of coplanar electrodes can be simultaneously capacitively detected and dielectrophoretically (DEP) actuated when the high (1.45 GHz) and low (100 kHz-20 MHz) frequency electromagnetic fields are concurrently applied through the same set of electrodes. Assuming a simple model in which the only forces acting upon the particles are apparent gravity, hydrodynamic lift, DEP force, and fluid drag, actuated particle trajectories can be obtained as numerical solutions of the equations of motion. Numerically calculated changes of particle elevations resulting from the actuation simulated in this way agree with the corresponding elevation changes estimated from the electronic signatures generated by the experimentally actuated particles. This verifies the model and confirms the correlation between the DEP force and the electronic signature profile. It follows that the electronic signatures can be used to quantify the actuation that the dielectric particle experiences as it traverses the electrode region. Using this principle, particles with different dielectric properties can be effectively identified based exclusively on their signature profile. This approach was used to differentiate viable from non-viable yeast cells (Saccharomyces cerevisiae). V C 2012 American Institute of Physics.

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Dielectrophoretic separation of colorectal cancer cells

Cited by 98 publications

References 46 publications

ApoStream™, a new dielectrophoretic device for antibody independent isolation and recovery of viable cancer cells from blood

ApoStream™, a new dielectrophoretic device for antibody independent isolation and recovery of viable cancer cells from blood

Human oral cancer cells with increasing tumorigenic abilities exhibit higher effective membrane capacitance

Electronic detection of dielectrophoretic forces exerted on particles flowing over interdigitated electrodes

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