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      Experimental Study on the Viscoelastic Flow Mixing in Microfluidics

      , 1 , 2 , , 3 , a , 3 , 3

      BIO Integration


      Microfluidics, viscoelastic flow, mixing

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          Background: The study of blood flow in vessels is always crucial to understand cardiovascular diseases such as arrhythmias, coronary artery disease and deep vein thrombosis. A viscoelastic fluid in a microchannel is modeled for the blood flow study.

          Methods: In this paper, we modeled the blood flow through a viscoelastic fluid in a microfluidic channel. The flow properties, especially the flow pattern and transient mixing of two fluid streams in a T-shaped microchannel, are experimentally studied.

          Results: It was found that the viscoelastic fluid has a transiently unstable flow pattern compared to the normal Newtonian fluid, and the mixing is also increased due to its elastic property. Similar to the pulsatile blood flow, the fluid is driven under a periodically pulsed stimulus, and the flow pattern and transient mixing are compared at different flow rates and driving period conditions.

          Conclusions: The integration of microfluidic technology with the blood flow research could provide a new approach to understand the related disease mechanism, which can also be used to analyze the drug mixing and delivery in the blood flow.

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          Most cited references 40

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          Microfluidic scaffolds for tissue engineering.

          Most methods to culture cells in three dimensions depend on a cell-seedable biomaterial to define the global structure of the culture and the microenvironment of the cells. Efforts to tailor these scaffolds have focused on the chemical and mechanical properties of the biomaterial itself. Here, we present a strategy to control the distributions of soluble chemicals within the scaffold with convective mass transfer via microfluidic networks embedded directly within the cell-seeded biomaterial. Our presentation of this strategy includes: a lithographic technique to build functional microfluidic structures within a calcium alginate hydrogel seeded with cells; characterization of this process with respect to microstructural fidelity and cell viability; characterization of convective and diffusive mass transfer of small and large solutes within this microfluidic scaffold; and demonstration of temporal and spatial control of the distribution of non-reactive solutes and reactive solutes (that is, metabolites) within the bulk of the scaffold. This approach to control the chemical environment on a micrometre scale within a macroscopic scaffold could aid in engineering complex tissues.
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            Microchip-based immunomagnetic detection of circulating tumor cells.

            Screening for circulating tumor cells (CTCs) in blood has been an object of interest for evidence of progressive disease, status of disease activity, recognition of clonal evolution of molecular changes and for possible early diagnosis of cancer. We describe a new method of microchip-based immunomagnetic CTC detection, in which the benefits of both immunomagnetic assay and the microfluidic device are combined. As the blood sample flows through the microchannel closely above arrayed magnets, cancer cells labeled with magnetic nanoparticles are separated from blood flow and deposited at the bottom wall of the glass coverslip, which allows direct observation of captured cells with a fluorescence microscope. A polydimethylsiloxane (PDMS)-based microchannel fixed on a glass coverslip was used to screen blood samples. The thin, flat dimensions of the microchannel, combined with the sharp magnetic field gradient in the vicinity of arrayed magnets with alternate polarities, lead to an effective capture of labeled cells. Compared to the commercially available CellSearch™ system, fewer (25%) magnetic particles are required to achieve a comparable capture rate, while the screening speed (at an optimal blood flow rate of 10 mL h(-1)) is more than five times faster than those reported previously with a microchannel-based assay. For the screening experiment, blood drawn from healthy subjects into CellSave™ tubes was spiked with cultured cancer cell lines of COLO205 and SKBR3. The blood was then kept at room temperature for 48 hours before the screening, emulating the actual clinical cases of blood screening. Customized Fe(3)O(4) magnetic nanoparticles (Veridex Ferrofluid™) conjugated to anti-epithelial cell adhesion molecule (EpCAM) antibodies were introduced into the blood samples to label cancer cells, and the blood was then run through the microchip device to capture the labelled cells. After capture, the cells were stained with fluorescent labelled anti-cytokeratin, DAPI and anti-CD45. Subsequent immunofluorescence images were taken for the captured cells, followed by comprehensive computer aided analysis based on fluorescence intensities and cell morphology. Rare cancer cells (from ∼1000 cells down to ∼5 cells per mL) with very low tumor cell to blood cell ratios (about 1 : 10(7) to 10(9), including red blood cells) were successfully detected. Cancer cell capture rates of 90% and 86% were demonstrated for COLO205 and SKBR3 cells, respectively.
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              A PDMS/paper/glass hybrid microfluidic biochip integrated with aptamer-functionalized graphene oxide nano-biosensors for one-step multiplexed pathogen detection.

              Infectious pathogens often cause serious public health concerns throughout the world. There is an increasing demand for simple, rapid and sensitive approaches for multiplexed pathogen detection. In this paper we have developed a polydimethylsiloxane (PDMS)/paper/glass hybrid microfluidic system integrated with aptamer-functionalized graphene oxide (GO) nano-biosensors for simple, one-step, multiplexed pathogen detection. The paper substrate used in this hybrid microfluidic system facilitated the integration of aptamer biosensors on the microfluidic biochip, and avoided complicated surface treatment and aptamer probe immobilization in a PDMS or glass-only microfluidic system. Lactobacillus acidophilus was used as a bacterium model to develop the microfluidic platform with a detection limit of 11.0 cfu mL(-1). We have also successfully extended this method to the simultaneous detection of two infectious pathogens - Staphylococcus aureus and Salmonella enterica. This method is simple and fast. The one-step 'turn on' pathogen assay in a ready-to-use microfluidic device only takes ~10 min to complete on the biochip. Furthermore, this microfluidic device has great potential in rapid detection of a wide variety of different other bacterial and viral pathogens.

                Author and article information

                BIO Integration
                Compuscript (Ireland )
                01 January 2021
                01 December 2020
                : 1
                : 4
                : 147-155
                1The First Affiliated Hospital of Sun Yat-Sen University, Sun Yat-Sen University, Guangzhou 510080, China
                2School of Engineering and Applied Science, Harvard University, Cambridge, MA 02138, USA
                3School of Physics and Material Science, Guangzhou University, Guangzhou 510006 China
                Author notes
                *Correspondence to: Meng Zhang, E-mail: meng.zhang_china@ 123456outlook.com ; Wu Zhang, E-mail: zh0002wu@ 123456outlook.com

                aWu Zhang have contributed equally in this manuscript as the co-first author.

                Copyright © 2020 The Authors

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See https://bio-integration.org/copyright-and-permissions/

                Self URI (journal-page): https://bio-integration.org/
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