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      Cell specific variation in viability in suspension in in vitro Poiseuille flow conditions

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          Abstract

          The influence of Poiseuille flow on cell viability has applications in the areas of cancer metastasis, lab-on-a-chip devices and flow cytometry. Indeed, retaining cell viability is important in the emerging field of adoptive cell therapy, as cells need to be returned to patients’ bodies, while the viability of other cells, which are perhaps less accustomed to suspension in a fluidic environment, is important to retain in flow cytometers and other such devices. Despite this, it is unclear how Poiseuille flow affects cell viability. Following on from previous studies which investigated the viability and inertial positions of circulating breast cancer cells in identical flow conditions, this study investigated the influence that varying flow rate, and the corresponding Reynolds number has on the viability of a range of different circulating cells in laminar pipe flow including primary T-cells, primary fibroblasts and neuroblastoma cells. It was found that Reynolds numbers as high as 9.13 had no effect on T-cells while the viabilities of neuroblastoma cells and intestinal fibroblasts were significantly reduced in comparison. This indicates that in vitro flow devices need to be tailored to cell-specific flow regimes.

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          Most cited references47

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          Inertial microfluidics.

          Despite the common wisdom that inertia does not contribute to microfluidic phenomena, recent work has shown a variety of useful effects that depend on fluid inertia for applications in enhanced mixing, particle separation, and bioparticle focusing. Due to the robust, fault-tolerant physical effects employed and high rates of operation, inertial microfluidic systems are poised to have a critical impact on high-throughput separation applications in environmental cleanup and physiological fluids processing, as well as bioparticle focusing applications in clinical diagnostics. In this review I will discuss the recent accelerated progress in developing prototype inertial microfluidic systems for a variety of applications and attempt to clarify the fundamental fluid dynamic effects that are being exploited. Finally, since this a nascent area of research, I will suggest some future promising directions exploiting fluid inertia on the microscale.
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            Fundamentals and applications of inertial microfluidics: a review.

            In the last decade, inertial microfluidics has attracted significant attention and a wide variety of channel designs that focus, concentrate and separate particles and fluids have been demonstrated. In contrast to conventional microfluidic technologies, where fluid inertia is negligible and flow remains almost within the Stokes flow region with very low Reynolds number (Re ≪ 1), inertial microfluidics works in the intermediate Reynolds number range (~1 < Re < ~100) between Stokes and turbulent regimes. In this intermediate range, both inertia and fluid viscosity are finite and bring about several intriguing effects that form the basis of inertial microfluidics including (i) inertial migration and (ii) secondary flow. Due to the superior features of high-throughput, simplicity, precise manipulation and low cost, inertial microfluidics is a very promising candidate for cellular sample processing, especially for samples with low abundant targets. In this review, we first discuss the fundamental kinematics of particles in microchannels to familiarise readers with the mechanisms and underlying physics in inertial microfluidic systems. We then present a comprehensive review of recent developments and key applications of inertial microfluidic systems according to their microchannel structures. Finally, we discuss the perspective of employing fluid inertia in microfluidics for particle manipulation. Due to the superior benefits of inertial microfluidics, this promising technology will still be an attractive topic in the near future, with more novel designs and further applications in biology, medicine and industry on the horizon.
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              Deformability-based cell classification and enrichment using inertial microfluidics.

              The ability to detect and isolate rare target cells from heterogeneous samples is in high demand in cell biology research, immunology, tissue engineering and medicine. Techniques allowing label-free cell enrichment or detection are especially important to reduce the complexity and costs towards clinical applications. Single-cell deformability has recently been recognized as a unique label-free biomarker for cell phenotype with implications for assessment of cancer invasiveness. Using a unique combination of fluid dynamic effects in a microfluidic system, we demonstrate high-throughput continuous label-free cell classification and enrichment based on cell size and deformability. The system takes advantage of a balance between deformability-induced and inertial lift forces as cells travel in a microchannel flow. Particles and droplets with varied elasticity and viscosity were found to have separate lateral dynamic equilibrium positions due to this balance of forces. We applied this system to successfully classify various cell types using cell size and deformability as distinguishing markers. Furthermore, using differences in dynamic equilibrium positions, we adapted the system to conduct passive, label-free and continuous cell enrichment based on these markers, enabling off-chip sample collection without significant gene expression changes. The presented method has practical potential for high-throughput deformability measurements and cost-effective cell separation to obtain viable target cells of interest in cancer research, immunology, and regenerative medicine.
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                Author and article information

                Contributors
                david.newport@ul.ie
                kieran.mcgourty@ul.ie
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                7 July 2021
                7 July 2021
                2021
                : 11
                : 13997
                Affiliations
                [1 ]GRID grid.10049.3c, ISNI 0000 0004 1936 9692, School of Engineering, Bernal Institute, , University of Limerick, ; Limerick, V94 T9PX Ireland
                [2 ]GRID grid.10049.3c, ISNI 0000 0004 1936 9692, Health Research Institute, , University of Limerick, ; Limerick, V94 T9PX Ireland
                [3 ]GRID grid.10049.3c, ISNI 0000 0004 1936 9692, School of Natural Sciences, Bernal Institute, , University of Limerick, ; Limerick, V94 T9PX Ireland
                Article
                91865
                10.1038/s41598-021-91865-1
                8263586
                34234155
                3efbe980-f86a-44bc-b52f-27949042b245
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 19 February 2021
                : 26 May 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100002081, Irish Research Council;
                Award ID: GOIPG/2016/1265
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2021

                Uncategorized
                cellular motility,cell death,biomedical engineering
                Uncategorized
                cellular motility, cell death, biomedical engineering

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