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      Microfluidic-Based Measurement Method of Red Blood Cell Aggregation under Hematocrit Variations

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          Abstract

          Red blood cell (RBC) aggregation and erythrocyte sedimentation rate (ESR) are considered to be promising biomarkers for effectively monitoring blood rheology at extremely low shear rates. In this study, a microfluidic-based measurement technique is suggested to evaluate RBC aggregation under hematocrit variations due to the continuous ESR. After the pipette tip is tightly fitted into an inlet port, a disposable suction pump is connected to the outlet port through a polyethylene tube. After dropping blood (approximately 0.2 mL) into the pipette tip, the blood flow can be started and stopped by periodically operating a pinch valve. To evaluate variations in RBC aggregation due to the continuous ESR, an EAI (Erythrocyte-sedimentation-rate Aggregation Index) is newly suggested, which uses temporal variations of image intensity. To demonstrate the proposed method, the dynamic characterization of the disposable suction pump is first quantitatively measured by varying the hematocrit levels and cavity volume of the suction pump. Next, variations in RBC aggregation and ESR are quantified by varying the hematocrit levels. The conventional aggregation index (AI) is maintained constant, unrelated to the hematocrit values. However, the EAI significantly decreased with respect to the hematocrit values. Thus, the EAI is more effective than the AI for monitoring variations in RBC aggregation due to the ESR. Lastly, the proposed method is employed to detect aggregated blood and thermally-induced blood. The EAI gradually increased as the concentration of a dextran solution increased. In addition, the EAI significantly decreased for thermally-induced blood. From this experimental demonstration, the proposed method is able to effectively measure variations in RBC aggregation due to continuous hematocrit variations, especially by quantifying the EAI.

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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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            Atherosclerosis, platelets and thrombosis in acute ischaemic heart disease.

            Atherosclerosis is the underlying reason for nearly all causes of coronary artery disease and peripheral arterial disease and many cases of stroke. Atherosclerosis is a systemic inflammatory process characterised by the accumulation of lipids and macrophages/lymphocytes within the intima of large arteries. The deposition of these blood borne materials and the subsequent thickening of the wall often significantly compromise the residual lumen leading to ischaemic events distal to the arterial stenosis. However, these initial fatty streak lesions may also evolve into vulnerable plaques susceptible to rupture or erosion. Plaque disruption initiates both platelet adhesion and aggregation on the exposed vascular surface and the activation of the clotting cascade leading to the so-called atherothrombotic process. Yet, platelets have also been shown to be transporters of regulatory molecules (micro-RNA), to drive the inflammatory response and mediate atherosclerosis progression. Here we discuss our current understanding of the pathophysiological mechanisms involved in atherogenesis - from fatty streaks to complex and vulnerable atheromas - and highlight the molecular machinery used by platelets to regulate the atherogenic process, thrombosis and its clinical implications.
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              Emerging Risk Biomarkers in Cardiovascular Diseases and Disorders

              Present review article highlights various cardiovascular risk prediction biomarkers by incorporating both traditional risk factors to be used as diagnostic markers and recent technologically generated diagnostic and therapeutic markers. This paper explains traditional biomarkers such as lipid profile, glucose, and hormone level and physiological biomarkers based on measurement of levels of important biomolecules such as serum ferritin, triglyceride to HDLp (high density lipoproteins) ratio, lipophorin-cholesterol ratio, lipid-lipophorin ratio, LDL cholesterol level, HDLp and apolipoprotein levels, lipophorins and LTPs ratio, sphingolipids, Omega-3 Index, and ST2 level. In addition, immunohistochemical, oxidative stress, inflammatory, anatomical, imaging, genetic, and therapeutic biomarkers have been explained in detail with their investigational specifications. Many of these biomarkers, alone or in combination, can play important role in prediction of risks, its types, and status of morbidity. As emerging risks are found to be affiliated with minor and microlevel factors and its diagnosis at an earlier stage could find CVD, hence, there is an urgent need of new more authentic, appropriate, and reliable diagnostic and therapeutic markers to confirm disease well in time to start the clinical aid to the patients. Present review aims to discuss new emerging biomarkers that could facilitate more authentic and fast diagnosis of CVDs, HF (heart failures), and various lipid abnormalities and disorders in the future.
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                Author and article information

                Journal
                Sensors (Basel)
                Sensors (Basel)
                sensors
                Sensors (Basel, Switzerland)
                MDPI
                1424-8220
                06 September 2017
                September 2017
                : 17
                : 9
                : 2037
                Affiliations
                Department of Mechanical Engineering, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju 61452, Korea; yjkang2011@ 123456chosun.ac.kr ; Tel.: +82-62-230-7052; Fax: +82-62-230-7055
                Author information
                https://orcid.org/0000-0002-5047-3012
                Article
                sensors-17-02037
                10.3390/s17092037
                5620946
                28878199
                5a9b51a7-d42c-49e5-8c76-7bedf582bfec
                © 2017 by the author.

                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
                : 08 August 2017
                : 04 September 2017
                Categories
                Article

                Biomedical engineering
                microfluidic device,disposable suction pump,periodic on-off blood delivery,esr aggregation index (eai),rbc aggregation index (ai),erythrocyte sedimentation rate (esr)

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