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      Visualization and Measurements of Blood Cells Flowing in Microfluidic Systems and Blood Rheology: A Personalized Medicine Perspective

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          Abstract

          Hemorheological alterations in the majority of metabolic diseases are always connected with blood rheology disturbances, such as the increase of blood and plasma viscosity, cell aggregation enhancement, and reduction of the red blood cells (RBCs) deformability. Thus, the visualizations and measurements of blood cells deformability flowing in microfluidic devices (point-of-care devices) can provide vital information to diagnose early symptoms of blood diseases and consequently to be used as a fast clinical tool for early detection of biomarkers. For instance, RBCs rigidity has been correlated with myocardial infarction, diabetes mellitus, hypertension, among other blood diseases. In order to better understand the blood cells behavior in microfluidic devices, rheological properties analysis is gaining interest by the biomedical committee, since it is strongly dependent on the interactions and mechanical cells proprieties. In addition, the development of blood analogue fluids capable of reproducing the rheological properties of blood and mimic the RBCs behavior at in vitro conditions is crucial for the design, performance and optimization of the microfluidic devices frequently used for personalized medicine. By combining the unique features of the hemorheology and microfluidic technology for single-cell analysis, valuable advances in personalized medicine for new treatments and diagnosis approach can be achieved.

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          The present and future role of microfluidics in biomedical research.

          Microfluidics, a technology characterized by the engineered manipulation of fluids at the submillimetre scale, has shown considerable promise for improving diagnostics and biology research. Certain properties of microfluidic technologies, such as rapid sample processing and the precise control of fluids in an assay, have made them attractive candidates to replace traditional experimental approaches. Here we analyse the progress made by lab-on-a-chip microtechnologies in recent years, and discuss the clinical and research areas in which they have made the greatest impact. We also suggest directions that biologists, engineers and clinicians can take to help this technology live up to its potential.
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            The link between abdominal obesity, metabolic syndrome and cardiovascular disease.

            The prevalence of metabolic syndrome has increased dramatically in recent years, and the cluster of metabolic abnormalities it encompasses results in increased cardiovascular morbidity and mortality. The role of abdominal (visceral) obesity and the underlying molecular and cellular mechanisms central to this association have been the subject of intensive research in recent times. The aim of this review is to correlate data in this area, highlighting the central role of excess visceral fat and its secreted adipokines, and to review existing and emerging therapies. Data were generated from a search of the PubMed database using the terms 'abdominal obesity', 'metabolic syndrome', 'insulin resistance', 'adipokines', 'interleukin-6 (IL-6)', 'adiponectin', 'tumour necrosis factor-alpha (TNF-alpha)' and 'cardiovascular disease'. Metabolic syndrome is associated with a pro-inflammatory state, and the role of visceral obesity is thought to be central to this. Visceral obesity leads to alteration of the normal physiological balance of adipokines, insulin resistance, endothelial dysfunction and a pro-atherogenic state. In association with this, the presence of conventional cardiovascular risk factors such as hypertension, dyslipidaemia and smoking results in a significantly elevated cardiovascular and metabolic (cardiometabolic) risk. Better understanding of the molecular mechanisms central to this association has led to the development of potential therapeutic agents.
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              Blood rheology and hemodynamics.

              Blood is a two-phase suspension of formed elements (i.e., red blood cells [RBCs], white blood cells [WBCs], platelets) suspended in an aqueous solution of organic molecules, proteins, and salts called plasma. The apparent viscosity of blood depends on the existing shear forces (i.e., blood behaves as a non-Newtonian fluid) and is determined by hematocrit, plasma viscosity, RBC aggregation, and the mechanical properties of RBCs. RBCs are highly deformable, and this physical property significantly contributes to aiding blood flow both under bulk flow conditions and in the microcirculation. The tendency of RBCs to undergo reversible aggregation is an important determinant of apparent viscosity because the size of RBC aggregates is inversely proportional to the magnitude of shear forces; the aggregates are dispersed with increasing shear forces, then reform under low-flow or static conditions. RBC aggregation also affects the in vivo fluidity of blood, especially in the low-shear regions of the circulatory system. Blood rheology has been reported to be altered in various physiopathological processes: (1) Alterations of hematocrit significantly contribute to hemorheological variations in diseases and in certain extreme physiological conditions; (2) RBC deformability is sensitive to local and general homeostasis, with RBC deformability affected by alterations of the properties and associations of membrane skeletal proteins, the ratio of RBC membrane surface area to cell volume, cell morphology, and cytoplasmic viscosity. Such alterations may result from genetic disorders or may be induced by such factors as abnormal local tissue metabolism, oxidant stress, and activated leukocytes; and (3) RBC aggregation is mainly determined by plasma protein composition and surface properties of RBCs, with increased plasma concentrations of acute phase reactants in inflammatory disorders a common cause of increased RBC aggregation. In addition, RBC aggregation tendency can be modified by alterations of RBC surface properties because of RBC in vivo aging, oxygen-free radicals, or proteolytic enzymes. Impairment of blood fluidity may significantly affect tissue perfusion and result in functional deteriorations, especially if disease processes also disturb vascular properties.
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                Author and article information

                Journal
                J Pers Med
                J Pers Med
                jpm
                Journal of Personalized Medicine
                MDPI
                2075-4426
                26 November 2020
                December 2020
                : 10
                : 4
                : 249
                Affiliations
                [1 ]Center for MicroElectromechanical Systems (CMEMS-UMinho), Campus de Azurém, University of Minho, 4800-058 Guimarães, Portugal
                [2 ]Research Centre in Digitalization and Intelligent Robotics (CeDRI), Campus de Santa Apolónia, Instituto Politécnico de Bragança, 5300-253 Bragança, Portugal
                [3 ]MEtRICs, Mechanical Engineering Department, Campus de Azurém, University of Minho, 4800-058 Guimarães, Portugal; violeta.carvalho@ 123456dem.uminho.pt (V.C.); rl@ 123456dem.uminho.pt (R.L.)
                [4 ]Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal; id9385@ 123456alunos.uminho.pt
                [5 ]ALGORITMI Center (CAlg), University of Minho, 4800-058 Guimarães, Portugal; st@ 123456dps.uminho.pt
                [6 ]CEFT, Faculdade de Engenharia da Universidade do Porto (FEUP), Rua Dr. Roberto Frias, 4200-465 Porto, Portugal
                Author notes
                [†]

                Current address: INL—International Iberian Nanotechnology Laboratory, Av. Mestre José Veiga, 4715-330 Braga, Portugal.

                Author information
                https://orcid.org/0000-0002-3884-6496
                https://orcid.org/0000-0002-9447-4746
                https://orcid.org/0000-0001-7986-8934
                https://orcid.org/0000-0002-7464-3944
                https://orcid.org/0000-0003-3428-637X
                Article
                jpm-10-00249
                10.3390/jpm10040249
                7712771
                33256123
                0e0acb85-09cb-455f-9c1a-cbe7c2762836
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 22 September 2020
                : 23 November 2020
                Categories
                Review

                hemorheology,blood diseases,microfluidics,single-cell analysis,red blood cells deformability,blood analogues

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