Experimental study on flow and turbulence characteristics of jet impinging on cylinder using three-dimensional Lagrangian particle tracking velocimetry.

When a round jet impinges on a convex cylindrical surface, complex three-dimensional (3D) flow structures occur, accompanied by the Coanda effect. To characterize the flow and turbulence properties of the general system, ensemble averages of 3D Lagrangian particle tracking velocimetry measurements were taken. The radial bin-averaging method was used in post-processing the tracked particles and corresponding instantaneous velocity vectors to generate appropriate ensemble-averaged statistics. Two impinging angles were selected, and at a fixed Reynolds number, the ensemble-averaged volumetric velocity field and turbulent stress tensor components were measured. The flow and turbulence characteristics of the impinging jet on the cylinder were notably different based on the impinging angle, especially in the downstream region. Surprisingly, the attached wall jet with a half-elliptic shape was abruptly thickened in the wall-normal direction, similar to the axis switching phenomenon observed in elliptic jets in the case of oblique impingement. In the jet-impinging region, the flow spread in all directions with high mean vorticity values. With the development of a 3D curved wall jet, both the Coanda effect and centrifugal force played a significant role in the flow behavior. A notable feature of the self-preserving region was the similarity of mean velocity profiles with scaling by the maximum velocity and the jet half-width for both impinging angle cases. Local isotropy of turbulent normal stresses was observed in this region, supporting the existence of self-preservation in the 3D curved wall jet. The volumetric ensemble-averaged Reynolds stress tensor revealed strong inhomogeneous turbulence in the boundary layer region and the curvature effect on the Reynolds shear stress in the free shear layer.

Neural network ensemble model for prediction of erythrocyte sedimentation rate (ESR) using partial least squares regression.

The erythrocyte sedimentation rate (ESR) is a non-specific blood test for determining inflammatory conditions. However, the long measurement time (60 min) to obtain ESR is an obstacle for a prompt evaluation. In this study, to reduce the measurement time of ESR, deep neural networks (DNNs) were applied to the sedimentation tendency of blood samples. DNNs using multilayer perceptron (MLP), long short-term memory (LSTM), and gated recurrent unit (GRU) were assessed and compared to determine a suitable length of time for the input sequence. To avoid overfitting, a stacking ensemble learning was adopted, which combines multiple models by using a meta model. Four meta models were compared: mean, median, least absolute shrinkage and selection operator, and partial least squares regression (PLSR) schemes. From the empirical results, LSTM and GRU models have better prediction than MLP over sequence lengths of 5 to 20 min. The decrease in [Formula: see text] and [Formula: see text] of GRU and LSTM was attenuated after a sequence length of 15 min, so the input sequence length is determined as 15 min. In terms of the meta model, the statistical comparison suggests that GRU combined with PLSR (GRU-PLSR) is the best case. Then, the GRU-PLSR was tested for prediction of ESR data obtained from periodontitis patients to check its applicability to a specific disease. The Bland-Altman plot shows acceptable agreement between measured and predicted ESR values. Based on the results, the GRU-PLSR can predict ESR with improved performance within 15 min and has potential applicability to ESR data with inflammatory and non-inflammatory conditions.

Quantitative study for control of air-liquid segmented flow in a 3D-printed chip using a vacuum-driven system.

The formation of droplets or bubbles in a microfluidic system is a significant topic requiring device miniaturization and a small volume of samples. Especially, a two-phase segmented flow can be applied to micro-mixing for chemical reactions and the treatment of heat and mass transfer. In this study, a flow of liquid slugs and bubbles was generated in a 3D-printed chip and controlled by a single pump creating a vacuum at the outlet. The pump and chip device were integrated to form a simple and portable system. The size and flow rate of liquid slugs, obtained through image processing techniques, were analyzed considering several parameters related to hydraulic resistance and pressure drop. In addition, the effect of segmentation on mixing was observed by measuring the intensity change using two different colored inks. The hydraulic resistance of air and liquid flows can be controlled by changing the tube length of air flow and the viscosity of liquid flow. Because the total pressure drop along the channel was produced using a single pump at the outlet of the channel, the size and flow rate of the liquid slugs showed a near linear relation depending on the hydraulic resistances. In contrast, as the total pressure varied with the flow rate of the pump, the size of the liquid slugs showed a nonlinear trend. This indicates that the frequency of the liquid slug formation induced by the squeezed bubble may be affected by several forces during the development of the liquid slugs and bubbles. In addition, each volume of liquid slug segmented by the air is within the range of 10-1 to 2 µL for this microfluidic system. The segmentation contributes to mixing efficiency based on the increased homogeneity factor of liquid. This study provides a new insight to better understand the liquid slug or droplet formation and predict the segmented flow based on the relationship between the resistance, flow rate, and pressure drop.

Electrodynamic Force Derived in-Channel Separation and Detection of Au Nanoparticles Using an Electrochemical AC Microfluidic Channel.

In this study, we have established the separation of Au nanoparticles (AuNPs) using a symmetrical AC electric field applied-electrochemical microfluidic device composed of carbon channel and detection electrodes. The lateral movement of AuNPs in the channel under the AC field was analyzed by simulation using the mathematically derived equations, which were formulated from Newtonian fluid mechanics. It shows that the nanoparticles are precisely separated according to their respective mass or size difference in a short time. The experimental parameters affecting the separation and detection of AuNPs were optimized in terms of applied frequency, amplitude, flow rate, buffer concentration, pH dependency, and temperature. The final separation was performed at 1.0 V amplitude with 8.0 MHz frequency at 0.4 µL/min flow rate for the separation, and the potential of 1.0 V was applied for the amperometric detection of AuNPs in a 0.1 M PBS. Before and after the separation, AuNPs (diameter range: 3-60 nm) were confirmed by UV-visible spectroscopy and transmission electron microscopy. In this case, the separation resolution was 3 nm with an enhanced separation efficiency of up to 597,503 plates/m for the AuNPs. In addition, the amperometric current response of the detection electrode under the AC field application was also enhanced by the sensitivity 5-fold compared with the absence of the AC field.

3D printed microfluidic viscometer based on the co-flowing stream.

Considering the role of viscosity in the dynamics of physical, chemical, and biological systems, accurate measurement of viscosity is essential. Although many conventional viscometers have been widely used, these conventional viscometers suffer from some drawbacks. In this study, a three-dimensional (3D) printed microfluidic viscometer was proposed based on the estimation of the pressure between two fluids to easily measure viscosity with small samples. The 3D printed microfluidic viscometer can be fabricated through amine-epoxy bonding on 3D printed blocks. By separately delivering samples and reference fluids into two inlets, an interfacial line could be induced. Based on the relation between the pressure ratio and the width of the reference flow, the viscosity (µ) of the sample can be estimated by measuring the relative width of the reference flow. The relation between the pressure and interfacial width between test samples and reference flows in the 3D printed microfluidic viscometers was analyzed by experiment and simulation to determine the effects of the mesh-like pattern of the 3D printed viscometers on the pressure estimation. To validate the proposed method, the viscosity values of glycerol mixtures measured by the 3D printed viscometer were compared with those measured by a conventional viscometer. As an application of the 3D printed viscometer, the viscosity curves for blood samples collected from diabetic and non-diabetic patients depending on their shear rates were compared. As expected, a high blood viscosity in the diabetic group was observed. Based on the experimental demonstrations, the 3D printed viscometer has strong potential to develop portable viscometers that can be translated to commercial outcomes.

Variations in pulsatile flow around stenosed microchannel depending on viscosity.

In studying blood flow in the vessels, the characteristics of non-Newtonian fluid are important, considering the role of viscosity in rheology. Stenosis, which is an abnormal narrowing of the vessel, has an influence on flow behavior. Therefore, analysis of blood flow in stenosed vessels is essential. However, most of them exist as simulation outcomes. In this study, non-Newtonian fluid was observed in stenosed microchannels under the pulsatile flow condition. A polydimethylsiloxane channel with 60% stenosis was fabricated by combining an optic fiber and a petri dish, resembling a mold. Three types of samples were prepared by changing the concentrations of xanthan gum, which induces a shear thinning effect (phosphate buffered saline (PBS) solution as the Newtonian fluid and two non-Newtonian fluids mimicking normal blood and highly viscous blood analog). The viscosity of the samples was measured using a Y-shaped microfluidic viscometer. Thereafter, velocity profiles were analyzed under the pulsatile flow condition using the micro-particle image velocimetry (PIV) method. For the Newtonian fluid, the streamline was skewed more to the wall of the channel. The velocity profile of the non-Newtonian fluid was generally blunter than that of the Newtonian fluid. A highly oscillating wall shear stress (WSS) during the pulsatile phase may be attributed to such a bluntness of flow under the same wall shear rate condition with the Newtonian fluid. In addition, a highly viscous flow contributes to the variation in the WSS after passing through the stenosed structures. A similar tendency was observed in simulation results. Such a variation in the WSS was associated with plaque instability or rupture and damage of the tissue layer. These results, related to the influence on the damage to the endothelium or stenotic lesion, may help clinicians understand relevant mechanisms.

Quantitative Analysis of Helical Flow with Accuracy Using Ultrasound Speckle Image Velocimetry: In Vitro and in Vivo Feasibility Studies.

Venous valve dysfunction and induced secondary abnormal flows are closely associated with venous diseases. Thus, detailed analysis of venous valvular flow is invaluable from biological and medical perspectives. However, most of the previous studies on venous perivalvular flows were based on qualitative analysis. On the contrary, quantitative analysis of perivalvular flows has not been fully understood. In this study, we used the ultrasound speckle image velocimetry (SIV) technique, which utilizes the speckle patterns of red blood cells (RBCs) created by ultrasound waves to measure 3-D valvular flows quantitatively. The flow structures obtained with the proposed SIV technique for an in vitro model were compared with those obtained by numerical simulation and the color Doppler method to validate the measurement accuracy of the ultrasound SIV technique. Blood flow in the human great saphenous vein was then measured at various distances from the valve with and without exercise. 3-D valvular flow was analyzed in accordance with the dimensionless index, helical intensity. The results obtained by the proposed method matched well with those obtained by numerical simulation and the color Doppler method. The hemodynamic characteristics of 3-D valvular helical flow which were analyzed experimentally using the SIV method would be used for quantitative diagnosis of venous valvular diseases.

Characteristics of pulsatile flows in curved stenosed channels.

Spatial and temporal variations of the hemodynamic features occur under pulsatile conditions in complex vessel geometry. Wall shear stress affected by the disturbed flow can result in endothelial cell dysfunction, which leads to atherogenesis and thrombosis. Therefore, detailed understanding of the hemodynamic characteristics in a curved stenosed channel is highly important when examining the pathological effects of hemodynamic phenomena on the progression of atherosclerosis. The present study measures the velocity fields of pulsatile flows with three different Reynolds numbers in 3D curved vessel models with stenosis using time-resolved particle image velocimetry (PIV). Three different models were cast in PDMS polymer using models made by a 3D printer with different bend angles of 0°, 10°, and 20° between the longitudinal axes at the upstream and downstream of the stenosis. To investigate the 3D flow structures, a stack of 2D velocity fields was obtained by adjusting the position of the laser sheet along the Z-direction. The structures of flow fields in the stenosed models were analyzed using the distribution of the shearing strain as well as the skewness and full width at half maximum of the velocity profile. To support experiment results, distributions of pressure and 3D vortex in the curved stenosed channels were estimated by conducting the numerical simulation. These results indicate that the curvature of the tube considerably influences the skewness of the flow, and the shear stress is intensified near the outer curvature wall due to centrifugal force. The results would be helpful in understanding the effects of geometrical factors on plaque rupture and severe cardiovascular diseases.

Microfluidic measurement for blood flow and platelet adhesion around a stenotic channel: Effects of tile size on the detection of platelet adhesion in a correlation map.

Platelet aggregation affects the surrounding blood flow and usually occurs where a blood vessel is narrowed as a result of atherosclerosis. The relationship between blood flow and platelet aggregation is not yet fully understood. This study proposes a microfluidic method to measure the velocity and platelet aggregation simultaneously by combining the micro-particle image velocimetry technique and a correlation mapping method. The blood flow and platelet adhesion procedure in a stenotic micro-channel with 90% severity were observed for a relatively long period of 4 min. In order to investigate the effect of tile size on the detection of platelet adhesion, 2D correlation coefficients were evaluated with binary images obtained by manual labeling and the correlation mapping method with different sizes of the square tile ranging from 3 to 50 pixels. The maximum 2D correlation coefficient occurred with the optimum tile size of 5 × 5 pixels. Since the blood flow and platelet aggregation are mutually influenced by each other, blood flow and platelet adhesion were continuously varied. When there was no platelet adhesion (t = 0 min), typical blood flow is observed. The blood flow passes through the whole channel smoothly, and jet-like flow occurs in the post-stenosis region. However, the flow pattern changes when platelet adhesion starts at the stenosis apex and after the stenosis. These adhesions induce narrow high velocity regions to become wider over a range of area from upstream to downstream of the stenosis. Separated jet-like flows with two high velocity regions are also created. The changes in flow patterns may alter the patterns of platelet adhesion. As the area of the plate adhesion increases, the platelets plug the micro-channel and there is only a small amount of blood flow, finally. The microfluidic method could provide new insights for better understanding of the interactions between platelet aggregation and blood flow in various physiological conditions.

Microfluidic system for monitoring temporal variations of hemorheological properties and platelet adhesion in LPS-injected rats.

Sepsis causes multiple organs failures and eventually death. Changes in blood constituents due to sepsis lead to alterations in hemorheological properties, and cell adhesiveness. In this study, a new microfluidic system is proposed to measure temporal variations in biophysical properties of blood after injecting lipopolysaccharide (LPS) into a rat extracorporeal model under ex vivo condition. To measure blood viscosity, the interfacial line between blood and a reference fluid is formed in a Y-shaped channel. Based on the relation between interfacial width and pressure ratio, the temporal variation in blood viscosity is estimated. Optical images of blood flows are analyzed by decreasing flow rate for examination of red blood cell (RBC) aggregation. Platelets initiated by shear acceleration around the stenosis adhere to the post-stenosed region. By applying a correlation map that visualizes the decorrelation of the streaming blood flow, the area of adhered platelets can be quantitatively attained without labeling of platelets. To assess sepsis inflammation, conventional biomarkers (PCT and IL-8) are also monitored. The increasing tendency for blood viscosity, RBC aggregation, platelet adhesion, and septic biomarkers are observed after LPS injection. This microfluidic system would be beneficial for monitoring the changes in hemorheological properties and platelet activation caused by sepsis.

Comparison of the tracheal systems of Anopheles sinensis and Aedes togoi larvae using synchrotron X-ray microscopic computed tomography (respiratory system of mosquito larvae using SR-µCT).

Mosquito-borne diseases, such as malaria, dengue fever, and Zika virus, are serious global health issues. Vector control may be an important strategy in reducing the mortality caused by these diseases. The respiratory system of mosquito larvae in the water has to inhale atmospheric oxygen as aquatic organisms. In this study, the three-dimensional (3D) structures of the dorsal longitudinal trunks (DLTs) of the tracheal systems of Anopheles sinensis and Aedes togoi were compared using synchrotron X-ray microscopic computed tomography. DLT respiratory frequencies were also investigated. Interestingly, the larvae of the two mosquito species exhibit tracheal systems that are both morphologically and functionally distinct. A. sinensis hangs horizontally under the water surface, and has a smaller DLT volume than A. togoi. In contrast, A. togoi hangs upside down using a siphon by fixing its tip to the water surface. The frequency of peristaltic movement in A. togoi is higher than that of A. sinensis. These differences in the structures and breathing behaviors of the respiratory systems of mosquito larvae provide new insights into the tracheal systems of mosquito larvae, which should help develop novel effective control strategies targeting mosquito larvae.

Three-dimensional structures of the tracheal systems of Anopheles sinensis and Aedes togoi pupae.

Mosquitoes act as a vector for the transmission of disease. The World Health Organization has recommended strict control of mosquito larvae because of their "few, fixed, and findable" features. The respiratory system of mosquito larvae and pupae in the water has a weak point. As aquatic organisms, mosquito larvae and pupae inhale atmosphere oxygen. However, the mosquito pupae have a non-feeding stage, unlike the larvae. Therefore, detailed study on the tracheal system of mosquito pupae is helpful for understanding their survival strategy. In this study, the three-dimensional (3D) structures of the tracheal systems of Anopheles sinensis and Aedes togoi pupae were comparatively investigated using synchrotron X-ray microscopic computed tomography. The respiratory frequencies of the dorsal trunks were also investigated. Interestingly, the pupae of the two mosquito species possess special tracheal systems of which the morphological and functional features are distinctively different. The respiratory frequency of Ae. togoi is higher than that of An. sinensis. These differences in the breathing phenomena and 3D structures of the respiratory systems of these two mosquito species provide an insight into the tracheal systems of mosquito pupae.

Variation in wall shear stress in channel networks of zebrafish models.

Physiological functions of vascular endothelial cells (ECs) vary depending on wall shear stress (WSS) magnitude, and the functional change affects the pathologies of various cardiovascular systems. Several in vitro and in vivo models have been used to investigate the functions of ECs under different WSS conditions. However, these models have technical limitations in precisely mimicking the physiological environments of ECs and monitoring temporal variations of ECs in detail. Although zebrafish (Danio rerio) has several strategies to overcome these technical limitations, zebrafish cannot be used as a perfect animal model because applying various WSS conditions on blood vessels of zebrafish is difficult. This study proposes a new zebrafish model in which various WSS can be applied to the caudal vein. The WSS magnitude is controlled by blocking some parts of blood-vessel networks. The accuracy and reproducibility of the proposed method are validated using an equivalent circuit model of blood vessels in zebrafish. The proposed method is applied to lipopolysaccharide (LPS)-stimulated zebrafish as a typical application. The proposed zebrafish model can be used as an in vivo animal model to investigate the relationship between WSS and EC physiology or WSS-induced cardiovascular diseases.

SPECT/CT analysis of splenic function in genistein-treated malaria-infected mice.

Spleen traps malaria-infected red blood cells, thereby leading to splenomegaly. Splenomegaly induces impairment in splenic function, i.e., rupture. Therefore, splenomegaly inhibition is required to protect the spleen. In our previous study, genistein was found to have an influence on malaria-induced splenomegaly. However, the effect of genistein in malaria-induced splenomegaly, especially on the function of spleen, has not been fully investigated. In this study, hematoxylin and eosin (H&E) staining images show that genistein partially prevents malaria-induced architectural disruption of spleen. In addition, genistein decreases transgenic Plasmodium parasites accumulation in the spleen. Genistein treatment can protect splenic function from impairment caused by malaria infection. To examine the functions of malaria-infected spleen, we employed single-photon emission computed tomography/computed tomography (SPECT/CT) technology. Red blood cells are specifically radiolabeled with Technetium-99m pertechnetate (99mTcO4-) and trapped inside the spleen. The standardized uptake values (SUVs) in the spleen of infected mice are higher than those of naive and genistein-treated mice. However, genistein reduces the malaria-induced trapping capacity of spleen for heat-damaged radiolabeled RBCs, while exhibiting a protective effect against malaria. Considering these results, we suggested that genistein could be effectively used in combination therapy for malaria-induced splenic impairment.

Microfluidics for simultaneous quantification of platelet adhesion and blood viscosity.

Platelet functions, including adhesion, activation, and aggregation have an influence on thrombosis and the progression of atherosclerosis. In the present study, a new microfluidic-based method is proposed to estimate platelet adhesion and blood viscosity simultaneously. Blood sample flows into an H-shaped microfluidic device with a peristaltic pump. Since platelet aggregation may be initiated by the compression of rotors inside the peristaltic pump, platelet aggregates may adhere to the H-shaped channel. Through correlation mapping, which visualizes decorrelation of the streaming blood flow, the area of adhered platelets (APlatelet) can be estimated without labeling platelets. The platelet function is estimated by determining the representative index IA·T based on APlatelet and contact time. Blood viscosity is measured by monitoring the flow conditions in the one side channel of the H-shaped device. Based on the relation between interfacial width (W) and pressure ratio of sample flows to the reference, blood sample viscosity (µ) can be estimated by measuring W. Biophysical parameters (IA·T, µ) are compared for normal and diabetic rats using an ex vivo extracorporeal model. This microfluidic-based method can be used for evaluating variations in the platelet adhesion and blood viscosity of animal models with cardiovascular diseases under ex vivo conditions.

Effect of diabetic duration on hemorheological properties and platelet aggregation in streptozotocin-induced diabetic rats.

Diabetes mellitus with abnormal glucose concentration is associated with changes in hemorheological properties, endothelial function, and platelets hyperactivity. Disturbances may significantly be responsible for diabetes-related vascular complications. In this study, hemorheological and hemodynamic properties were measured according to diabetic duration after streptozotocin treatment in rats. For ex vivo measurements, an extracorporeal model was adopted. Flow rate and blood viscosity were measured using a microfluidic device. Erythrocyte aggregation and morphological parameters of erythrocytes were measured by modified erythrocyte sedimentation rate and the phase-contrast holography under in vitro conditions. The platelet aggregation and mean pressure in the femoral artery were estimated under ex vivo conditions. Hemorheological properties including blood viscosity, erythrocyte aggregation and shape parameters for the control group are significantly different with those for diabetic groups. The changes with respect to diabetic duration were relatively unnoticeable. However, the platelet aggregation is strongly dependent on the diabetic duration. Based on these results, hyperglycemia exposure may induce hemorheological variations in early stages of diabetes mellitus. High platelet aggregation may become more pronounced according to the diabetic duration caused by variations in hemorheological properties resulting in endothelial dysfunction. This study would be helpful in understanding the effects of diabetic duration on biophysical properties.

X-ray PIV measurement of blood flow in deep vessels of a rat: An in vivo feasibility study.

X-ray PIV measurement is a noninvasive approach to measure opaque blood flows. However, it is not easy to measure real pulsatile blood flows in the blood vessels located at deep position of the body, because the surrounding tissues significantly attenuate the contrast of X-ray images. This study investigated the effect of surrounding tissues on X-ray beam attenuation by measuring the velocity fields of blood flows in deep vessels of a live rat. The decrease in image contrast was minimized by employing biocompatible CO2 microbubbles as tracer particles. The maximum measurable velocity of blood flows in the abdominal aorta of a rat model was found through comparative examination between the PIV measurement accuracy and the level of image contrast according to the input flow rate. Furthermore, the feasibility of using X-ray PIV to accurately measure in vivo blood flows was demonstrated by determining the velocity field of blood flows in the inferior vena cava of a rat. This study may serve as a reference in conducting in vivo X-ray PIV measurements of pulsatile blood flows in animal disease models and investigating hemodynamic characteristics and circulatory vascular diseases.

Association of Early Atherosclerosis with Vascular Wall Shear Stress in Hypercholesterolemic Zebrafish.

Although atherosclerosis is a multifactorial disease, the role of hemodynamic information has become more important. Low and oscillating wall shear stress (WSS) that changes its direction is associated with the early stage of atherosclerosis. Several in vitro and in vivo models were proposed to reveal the relation between the WSS and the early atherosclerosis. However, these models possess technical limitations in mimicking real physiological conditions and monitoring the developmental course of the early atherosclerosis. In this study, a hypercholesterolaemic zebrafish model is proposed as a novel experimental model to resolve these limitations. Zebrafish larvae are optically transparent, which enables temporal observation of pathological variations under in vivo condition. WSS in blood vessels of 15 days post-fertilisation zebrafish was measured using a micro particle image velocimetry (PIV) technique, and spatial distribution of lipid deposition inside the model was quantitatively investigated after feeding high cholesterol diet for 10 days. Lipids were mainly deposited in blood vessel of low WSS. The oscillating WSS was not induced by the blood flows in zebrafish models. The present hypercholesterolaemic zebrafish would be used as a potentially useful model for in vivo study about the effects of low WSS in the early atherosclerosis.

Hybrid System for Ex Vivo Hemorheological and Hemodynamic Analysis: A Feasibility Study.

Precise measurement of biophysical properties is important to understand the relation between these properties and the outbreak of cardiovascular diseases (CVDs). However, a systematic measurement for these biophysical parameters under in vivo conditions is nearly impossible because of complex vessel shape and limited practicality. In vitro measurements can provide more biophysical information, but in vitro exposure changes hemorheological properties. In this study, a hybrid system composed of an ultrasound system and microfluidic device is proposed for monitoring hemorheological and hemodynamic properties under more reasonable experimental conditions. Biophysical properties including RBC aggregation, viscosity, velocity, and pressure of blood flows are simultaneously measured under various conditions to demonstrate the feasibility and performance of this measurement system. The proposed technique is applied to a rat extracorporeal loop which connects the aorta and jugular vein directly. As a result, the proposed system is found to measure biophysical parameters reasonably without blood collection from the rat and provided more detailed information. This hybrid system, combining ultrasound imaging and microfluidic techniques to ex vivo animal models, would be useful for monitoring the variations of biophysical properties induced by chemical agents. It can be used to understand the relation between biophysical parameters and CVDs.

Microfluidic-based speckle analysis for sensitive measurement of erythrocyte aggregation: A comparison of four methods for detection of elevated erythrocyte aggregation in diabetic rat blood.

Biochemical alterations in the plasma and red blood cell (RBC) membrane of diabetic blood lead to excessive erythrocyte aggregation (EA). EA would significantly impede the blood flow and increase the vascular flow resistance contributing to peripheral vascular diseases. In this study, a simple microfluidic-based method is proposed to achieve sensitive detection of hyperaggregation. When a blood sample is delivered into the device, images of blood flows are obtained with a short exposure time for a relatively long measuring time. A micro-particle image velocimetry technique was employed to monitor variation of the flow rate of blood as a function of time. Given that EA formation in the channel creates clear speckle patterns, the EA extent can be estimated by calculating a speckle area (ASpeckle) through a normalized autocovariance function. The hematocrit effect is assessed by comparing optical images transmitted through blood samples. EA variations caused by dextran treatment are quantitatively evaluated using characteristic time (λSpeckle) obtained by fitting the variations of ASpeckle. Other indices including number of RBCs in an aggregate (NRBC), characteristic time of erythrocyte sedimentation rate (λESR), and aggregation index estimated from ultrasound signals (AIEcho) are determined under different EA conditions using conventional techniques. The four different methods are applied to diabetic blood samples to compare their indices under hyperaggregation conditions. It is found that the proposed method can detect variation of EA reasonably, compared with conventional measurement techniques. These experimental demonstrations support the notion that the proposed method is capable of effectively monitoring the biophysical properties of diabetic blood.