Abstract: Red blood cells (RBCs) exhibit a unique deformability, which enables them to change shape reversibly in response to an external force. The deformability of RBCs allows them to flow in microvessels while transporting oxygen and carbon dioxide. In this review, we discussed the major determinants of RBC deformability, which include cell geometry, internal viscosity, rheological properties of the membrane, osmotic pressure, calcium, nitric oxide, temperature, ageing, and depletion of adenosine triphosphate. Additionally, we highlighted the various methods and techniques used to measure RBC deformability. Individual cell analyses (pipette aspiration and optical tweezers) and bulk cell analyses (ektacytometry, multiple channels) were…described and compared. Finally, we reviewed the correlation between RBC deformability and clinical outcomes such as diabetic microangiopathy.
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Abstract: A liquid biopsy is a simple and non-invasive biopsy that examines a range of information about a tumor through a simple blood sample. Due to its non-invasive nature, liquid biopsy has many outstanding clinical benefits, including repetitive sampling and examination, representation of whole mutations, observation of minimal residual disease etc. However, liquid biopsy requires various processes such as sample preparation, amplification, and target detection. These processes can be integrated onto microfluidic platforms, which may provide a sample-to-answer system. The present review provides a brief overview of liquid biopsies, a detailed review of the technologies in each process, and prospective concluding…remarks. Through this review, one can have a basic but cross-disciplinary understanding of liquid biopsy, as well as knowledge of new starting points for future research in each related area.
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Abstract: Red blood cell (RBC) deformability is greatly affected by the osmolality, and maximum deformability, which is determined as maximal elongation index (EImax ), is usually observed in isotonic conditions at high shear stresses (>20 Pa). Therefore, we examined osmotic RBC deformability over a range of shear stresses (0.5–20 Pa). We found that the RBC deformability at low shear stresses (1–3 Pa) was maximum in hypotonic conditions (225–250 mOsm/kg H2 O), which is slightly lower than the normal range of osmolality in plasma (290–310 mOsm/kg H2 O). The phenomenon that Omax (the osmolality at EImax ) is dependent on applied shear…stress could play an important role in microcirculation in which osmolality varies widely.
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Keywords: RBC, deformability, osmolality, shear stress, in vivo
Abstract: Lead is a ubiquitous, biohazardous, and toxic heavy metal that induces a broad range of physiological, biochemical, and behavioral dysfunctions. We investigated the effect of lead on hemorheological characteristics, including deformability and aggregation. We found that red blood cell (RBC) deformability was unaffected at low concentrations of lead-rich plasma, but showed a significant decrease at high concentrations even within 1 h of incubation. In addition, apparent alterations in RBC aggregation were observed with an increase in lead concentration and incubation time. These results highlight the influence of lead on hemorheology and microcirculation.
Abstract: Red blood cell (RBC) aggregation is greatly affected by cell deformability and reduced deformability and increased RBC aggregation are frequently observed in hypertension, diabetes mellitus, and sepsis, thus measurement of both these parameters is essential. In this study, we investigated the effects of cell deformability and fibrinogen concentration on disaggregating shear stress (DSS). The DSS was measured with varying cell deformability and geometry. The deformability of cells was gradually decreased with increasing concentration of glutaraldehyde (0.001~0.005%) or heat treatment at 49.0°C for increasing time intervals (0~7 min), which resulted in a progressive increase in the DSS. However, RBC rigidification by…either glutaraldehyde or heat treatment did not cause the same effect on RBC aggregation as deformability did. The effect of cell deformability on DSS was significantly increased with an increase in fibrinogen concentration (2~6 g/L). These results imply that reduced cell deformability and increased fibrinogen levels play a synergistic role in increasing DSS, which could be used as a novel independent hemorheological index to characterize microcirculatory diseases, such as diabetic complications with high sensitivity.
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Abstract: Silica nanomaterials (NMs) are widely used in semiconductor, agriculture, cosmetics, and biomedical applications, in addition to other industries. We investigated the toxic effect of silica NMs on rheological characteristics of human red blood cells (RBCs), including hemolysis, deformability, aggregation, and morphological changes. Red blood cells were exposed to silica nanoparticles (d =∼200 nm) or silica nanowires (d =∼200 nm, l = 1μ m or 10μ m) at a range of concentrations and incubation times. Rheological characteristics were measured using microfluidic-laser diffractometry and aggregometry. Overall, at a concentration greater than 12.5μ g/ml, the hemolytic activity was shown to be in the order of nanoparticles,…short nanowires, and long nanowires. Elongation index (EI) values were insignificant in the RBCs exposed to each of the silica NMs at a concentration of 12.5μ g/ml. Aggregation index (AI) values decreased in the short silica nanowires at a concentration of 12.5μ g/ml compared to other silica NMs. Therefore, the safe concentration of silica NMs for toxicity, in this study, was considered less than 12.5μ g/ml. These hemorheological results provided insight into the interaction between RBCs and silica NMs; they will also help assess the risk of NMs’ toxicity in the blood.
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Abstract: In the analysis of red blood cell (RBC) aggregation using optical detection, various shearing methods have been used to disperse RBCs in confined geometries. This study investigated RBC aggregation measurement in a microchip-stirring system by analysis of light transmission. A stirring-aided disaggregation mechanism in a microchip, consisting of a flat-cylindrical test chamber (D=4 mm, H=0.3 mm) and a magnetic stirrer (d=0.14 mm, l=2.2 mm), was used to generate a given shear which was large enough to disperse RBC aggregates, but not large enough to cause any mechanical hemolysis of cells. After stirring for 10 s followed by an abrupt halt…of the stirring, the intensity of the light transmitted through a microchip was measured with respect to time and analyzed. A comparative study was conducted with varying test chamber height and hematocrit. The AI and t1/2 as typical aggregation indices obtained by analysis of transmitted light, which showed a good reproducibility (coefficient of variation (CV)<2.8%, n=10), also were found to be nearly independent of the chamber dimensions (CV<3.4%). The present aggregometry also showed the similar results of aggregation indices with varying hematocrits compared to those obtained using a laser-assisted optical rotational cell analyzer (LORCA). The essential feature of the present design is the adoption of a disposable microchip requiring a minimum blood sample volume as small as 6 μl, which enables it to be used easily in a clinical setting.
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Keywords: Aggregometer, erythrocyte aggregation, hematocrit, light transmission, microchip stirring system
Abstract: Even though blood coagulation can be tested by various methods and techniques, the effect of RBC aggregation on blood coagulation is not fully understood. The present study monitored clot formation in a microchip-based light transmission aggregometer. Citrated blood samples with and without the addition of calcium ion solution were initially disaggregated by rotating a stirrer in the microchip. After abrupt stop of the rotating stirrer, the transmitted light intensity over time was recorded. The syllectogram (light intensity vs. time graph) manifested a rapid increase that is associated with RBC aggregation followed by a decrease that is associated with blood coagulation.…The time to reach the peak point was used as a new index of coagulation time (CT) and ranged from 200 to 500 seconds in the present measurements. The CT was inversely proportional to the concentration of fibrinogen, which enhances RBC aggregation. In addition, the CT was inversely proportional to the hematocrit, which is similar to the case of the prothrombin time (PT), as measured by a commercial coagulometer. Thus, we carefully concluded that RBC aggregation should be considered in tests of blood coagulation.
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Abstract: Single-walled carbon nanotubes (SWNTs) have been increasingly used in a variety of biomedical applications, such as in vivo delivery of drugs and tumor imaging. Potential exposure of SWNTs to human red blood cells (RBCs) may cause serious toxicity including alteration of mechanical properties of cells. The present study investigated the cellular response to exposure of SWNTs with measuring rheological characteristics of RBCs, including hemolysis, deformability, aggregation, and morphological changes. RBCs were exposed to two different dispersion-state samples (i.e. individual SWNTs and bundled SWNTs) in chitosan hydroxyphenyl acetamide (CHPA) solutions. The concentrations of SWNTs were carefully chosen to avoid any hemorheological…alterations due to hemolysis. Rheological characteristics were measured using microfluidic-laser diffractometry and aggregometry. Our results show that the bundled SWNTs had higher hemolytic activity than did the individual SWNTs. RBC aggregation apparently decreased as the concentration of SWNTs or incubation time increased. Additionally, bundled SWNTs caused significant alterations in the shape and fusion of RBCs. In conclusion, bundled SWNTs were found to be more toxic than individual SWNTs. These results provide important insights into the interactions between RBCs and SWNTs and will facilitate assessment of the risk of nanomaterial toxicity of blood.
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