On passing a non-Newtonian circulating tumor cell (CTC) through a deformation-based microfluidic chip (original) (raw)
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Various lab on a chip devices have been developed recently to detect and separate circulating tumour cells (CTCs) for early stage cancer detection. Because CTCs are extremely rare in the blood, next generation CTC microfilters aim at significant improvement in both efficiency and throughput. CTC microfilters based on cell deformability seem to be a promising direction. In the present research, we study a CTC passing event through a micro-filtering channel with various 3D geometries. The pressure signatures for different types of cells passing through different channels are characterized numerically. Specifically, five kinds of cross-sections, circular, square, triangular and two kinds of rectangular channels with aspect ratios of 2 and 5, are studied in this work. The total pressures for cells passing through the channels are calculated and reveal different behaviour from what is predicted by the static surface tension model. Among all five cross-sections studied, the circular cross-section features the highest critical pressure and thus is most suitable for high efficiency CTC separation. The square filtering channel provides the second largest critical pressure, and the triangular cross-section provides the least critical pressure among these three cross-sections. All these three cross-sections are better than the rectangular channels with aspect ratios of 2 and 5. For the rectangular channel, a high aspect ratio channel may lead to cell splitting at high speed, which will result in a periodic pressure signature. Our findings will provide valuable information for the design of next generation CTC microfilters.
Stiffness based enrichment of leukemia cells using microfluidics
APL Bioengineering
To improve the survival rate of cancer patients, new diagnosis strategies are necessary to detect lower levels of cancer cells before and after treatment regimens. The scarcity of diseased cells, particularly in residual disease after treatment, demands highly sensitive detection approaches or the ability to enrich the diseased cells in relation to normal cells. We report a label-free microfluidic approach to enrich leukemia cells from healthy cells using inherent differences in cell biophysical properties. The microfluidic device consists of a channel with an array of diagonal ridges that recurrently compress and translate flowing cells in proportion to cell stiffness. Using devices optimized for acute T cell leukemia model Jurkat, the stiffer white blood cells were translated orthogonally to the channel length, while softer leukemia cells followed hydrodynamic flow. The device enriched Jurkat leukemia cells from white blood cells with an enrichment factor of over 760. The sensitivity, specificity, and accuracy of the device were found to be >0:8. The values of sensitivity and specificity could be adjusted by selecting one or multiple outlets for analysis. We demonstrate that low levels of Jurkat leukemia cells (1 in 10 4 white blood cells) could be more quickly detected using flow cytometry by using the stiffness sorting pre-enrichment. In a second mode of operation, the device was implemented to sort resistive leukemia cells from both drug-sensitive leukemia cells and normal white blood cells. Therefore, microfluidic biomechanical sorting can be a useful tool to enrich leukemia cells that may improve downstream analyses.
Characterizing Deformability and Electrical Impedance of Cancer Cells in a Microfluidic Device
Analytical chemistry, 2018
Mechanical properties of cells, reflective of various biochemical characteristics such as gene expression and cytoskeleton, are promising label-free biomarkers for studying and characterizing cells. Electrical properties of cells, dependent on the cellular structure and content, are also label-free indicators of cell states and phenotypes. In this work, we have developed a microfluidic device that is able to simultaneously characterize the mechanical and electrical properties of individual biological cells in a high-throughput manner (>1000 cells/min). The deformability of MCF-7 breast cancer cells was characterized based on the passage time required for an individual cell to pass through a constriction smaller than the cell size. The total passage time can be divided into two components: the entry time required for a cell to deform and enter a constriction, which is dominated by the deformability of cells, and the transit time required for the fully deformed cell to travel insid...
Calibration of Circulating Tumor Cell’s Model in Narrow Flow
EPJ Web of Conferences
In this article our objective was to calibrate model of Circulating Tumor Cell (CTC). Different types of cancer produce different types of CTCs. For research purposes, we chose to set up the model according to MCF7 breast cancer cell lines, due to the availability of data from laboratory experiments. First, to obtain working model we used mechanics of our already existing RBC model, taking into consideration the differences between RBC and CTC. Next step was to find values for the elastic parameters of the cell model. We have chosen laboratory experiment where the deformability of breast cancer cell passing through narrow microfluidic channel was examined. The channel has similar dimensions as blood capillaries to mimic the in vivo environment. In order to achieve similar behavior of the cell’s model and the real cell in the experiment we needed to set fluid flow according to experimental data. This was achieved by adjusting the fluid force that is dependent on the volumetric flow rate...
Modeling of biological cells deformation in microfluidic systems
2015
Запропоновано методи моделювання деформації біологічних клітин у мікрофлюїдних пристроях. Описані передумови і цілі розроблення механічної моделі живої біологічної клітини для поліпшення моделювання та автоматизованого проектування пристроїв для мікрофлюідних пристроїв біоаналізу та діагностики. This paper is devoted to the modeling of biological cells deformation in microfluidic systems. The background and purposes of development of the mechanical model of the living biological cell to improve modelling and computer aided design of microfluidic devices for bioanalisys and diagnostics were described.
Biomicrofluidics, 2018
Cancer cell migration and invasion, which are involved in tumour metastasis, are hard to predict and control. Numerous studies have demonstrated that physical cues influence cancer cell migration and affect tumour metastasis. In this study, we proposed the use of a microchannel chip equipped with a number of vertical constrictions to produce periodic compression forces on cells passing through narrow channels. The chip with repeated vertical confinement was applied on adherent MHCC-97L liver cancer cells and suspended OCI-AML leukaemia cells to determine the migration ability of these cancer cells. Given the stimulation of the periodic mechanical confinement on-chip, the migration ability of cancer cells was promoted. Moreover, the migration speed increased as the stimulation was enhanced. Both AFM nanoindentation and optical stretching tests on cancer cells were performed to measure their mechanical property. After confinement stimulation, the cancer cells possessed higher deformab...