scholarly journals Microfluidic-Based Technique for Measuring RBC Aggregation and Blood Viscosity in a Continuous and Simultaneous Fashion

Micromachines ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 467 ◽  
Author(s):  
Yang Kang

Hemorheological properties such as viscosity, deformability, and aggregation have been employed to monitor or screen patients with cardiovascular diseases. To effectively evaluate blood circulating within an in vitro closed circuit, it is important to quantify its hemorheological properties consistently and accurately. A simple method for measuring red blood cell (RBC) aggregation and blood viscosity is proposed for analyzing blood flow in a microfluidic device, especially in a continuous and simultaneous fashion. To measure RBC aggregation, blood flows through three channels: the left wide channel, the narrow channel and the right wide channel sequentially. After quantifying the image intensity of RBCs aggregated in the left channel (<IRA>) and the RBCs disaggregated in the right channel (<IRD>), the RBC aggregation index (AIPM) is obtained by dividing <IRA> by <IRD>. Simultaneously, based on a modified parallel flow method, blood viscosity is obtained by detecting the interface between two fluids in the right wide channel. RBC aggregation and blood viscosity were first evaluated under constant and pulsatile blood flows. AIPM varies significantly with respect to blood flow rate (for both its amplitude and period) and the concentration of the dextran solution used. According to our quantitative comparison between the proposed aggregation index (AIPM) and the conventional aggregation index (AICM), it is found that AIPM provides consistent results. Finally, the suggested method is employed to obtain the RBC aggregation and blood viscosity of blood circulating within an in vitro fluidic circuit. The experimental results lead to the conclusion that the proposed method can be successfully used to measure RBC aggregation and blood viscosity, especially in a continuous and simultaneous fashion.

2021 ◽  
Vol 20 (1) ◽  
pp. 17-24
Author(s):  
I. M. Kadanova ◽  
A. I. Neznanov ◽  
A. Е. Lugovtsov ◽  
Yu. I. Gurfinkel ◽  
A. A. Pigurenko ◽  
...  

Introduction. Blood microcirculation and its microrheologic properties are impaired in cardiovascular diseases. Microrheologic properties are characterized by the red blood cells (RBC) ability to aggregate and disaggregate. Therefore, the correlation studies between RBC aggregation and microcirculation disorders in pathologies are of interest for the development of theoretical concepts related to blood flow and for clinical practice.Aim. To analyze the correlation between capillary blood flow parameters measured in vivo and microrheologic blood parameters measured in vitro in patients suffering arterial hypertension (AH) and coronary heart disease (CHD).Materials and methods. We studied 3 groups of people: patients suffering AH, patients suffering AH+CHD and healthy donors. The characteristic aggregation time and aggregation index were measured in vitro by laser aggregometry. Analysis of capillary blood velocity (CBV) and assessment of the presence and absence of RBC aggregates in the nail bed capillaries were performed in vivo using vital digital capillaroscopy (VDC).Results. RBC aggregation for groups of patients suffering AH and AH+CHD was increased compared to the control group. Thus, in these patients groups, the characteristic aggregation time significantly decreases by an average of (38±13) %. Comparison of the results obtained using in vitro and in vivo methods showed the aggregation index for individuals with high CBV was significantly lower than for individuals with low CBV. The tendency is that the number of aggregates in the capillaries increases with a decrease in CBV.Conclusion. RBC aggregation is increased in groups of patients suffering AH and AH+CHD compared to the control group. The correlation between parameters measured in vitro and in vivo is evident for patients divided into subgroups according to parameters measured using the VDC. The obtained results allow us to conclude that the used methods are applicable in clinical practice.


Micromachines ◽  
2019 ◽  
Vol 10 (9) ◽  
pp. 577 ◽  
Author(s):  
Yang Jun Kang

Aggregation of red blood cells (RBCs) varies substantially depending on changes of several factors such as hematocrit, membrane deformability, and plasma proteins. Among these factors, hematocrit has a strong influence on the aggregation of RBCs. Thus, while measuring RBCs aggregation, it is necessary to monitor hematocrit or, additionally, the effect of hematocrit (i.e., blood viscosity or pressure). In this study, the sequential measurement method of pressure and RBC aggregation is proposed by quantifying blood flow (i.e., velocity and image intensity) through a microfluidic device, in which an air-compressed syringe (ACS) is used to control the sample injection. The microfluidic device used is composed of two channels (pressure channel (PC), and blood channel (BC)), an inlet, and an outlet. A single ACS (i.e., air suction = 0.4 mL, blood suction = 0.4 mL, and air compression = 0.3 mL) is employed to supply blood into the microfluidic channel. At an initial time (t < 10 s), the pressure index (PI) is evaluated by analyzing the intensity of microscopy images of blood samples collected inside PC. During blood delivery with ACS, shear rates of blood flows vary continuously over time. After a certain amount of time has elapsed (t > 30 s), two RBC aggregation indices (i.e., SEAI: without information on shear rate, and erythrocyte aggregation index (EAI): with information on shear rate) are quantified by analyzing the image intensity and velocity field of blood flow in BC. According to experimental results, PI depends significantly on the characteristics of the blood samples (i.e., hematocrit or base solutions) and can be used effectively as an alternative to blood viscosity. In addition, SEAI and EAI also depend significantly on the degree of RBC aggregation. In conclusion, on the basis of three indices (two RBC aggregation indices and pressure index), the proposed method is capable of measuring RBCs aggregation consistently using a microfluidic device.


Micromachines ◽  
2018 ◽  
Vol 9 (10) ◽  
pp. 475 ◽  
Author(s):  
Yang Kang

Biophysical properties are widely used to detect pathophysiological processes of vascular diseases or clinical states. For early detection of cardiovascular diseases, it is necessary to simultaneously measure multiple biophysical properties in a microfluidic environment. However, a microfluidic-based technique for measuring multiple biophysical properties has not been demonstrated. In this study, a simple measurement method was suggested to quantify three biophysical properties of blood, including red blood cell (RBC) deformability, RBC aggregation, and hematocrit. To demonstrate the suggested method, a microfluidic device was constructed, being composed of a big-sized channel (BC), a parallel micropillar (MP), a main channel, a branch channel, inlet, and outlets. By operating a single syringe pump, blood was supplied into the inlet of the microfluidic device, at a periodic on-off profile (i.e., period = 240 s). The RBC deformability index (DI) was obtained by analyzing the averaged blood velocity in the branch channel. Additionally, the RBC aggregation index (AIN) and the hematocrit index (HiBC) were measured by analyzing the image intensity of blood flows in the MP and the BC, respectively. The corresponding contributions of three influencing factors, including the turn-on time (Ton), the amplitude of blood flow rate (Q0), and the hematocrit (Hct) on the biophysical indices (DI, AIN, and HiBC) were evaluated quantitatively. As the three biophysical indices varied significantly with respect to the three factors, the following conditions (i.e., Ton = 210 s, Q0 = 1 mL/h, and Hct = 50%) were maintained for consistent measurement of biophysical properties. The proposed method was employed to detect variations of biophysical properties depending on the concentrations of autologous plasma, homogeneous hardened RBCs, and heterogeneous hardened RBCs. Based on the observations, the proposed method exhibited significant differences in biophysical properties depending on base solutions, homogeneous hardened RBCs (i.e., all RBCs fixed with the same concentration of glutaraldehyde solution), and heterogeneous hardened RBCs (i.e., partially mixed with normal RBCs and homogeneous hardened RBCs). Additionally, the suggested indices (i.e., DI, AIN, and HiBC) were effectively employed to quantify three biophysical properties, including RBC deformability, RBC aggregation, and hematocrit.


2021 ◽  
Vol 11 (16) ◽  
pp. 7260
Author(s):  
Yang Jun Kang

Determination of blood viscosity requires consistent measurement of blood flow rates, which leads to measurement errors and presents several issues when there are continuous changes in hematocrit changes. Instead of blood viscosity, a coflowing channel as a pressure sensor is adopted to quantify the dynamic flow of blood. Information on blood (i.e., hematocrit, flow rate, and viscosity) is not provided in advance. Using a discrete circuit model for the coflowing streams, the analytical expressions for four properties (i.e., pressure, shear stress, and two types of work) are then derived to quantify the flow of the test fluid. The analytical expressions are validated through numerical simulations. To demonstrate the method, the four properties are obtained using the present method by varying the flow patterns (i.e., constant flow rate or sinusoidal flow rate) as well as test fluids (i.e., glycerin solutions and blood). Thereafter, the present method is applied to quantify the dynamic flows of RBC aggregation-enhanced blood with a peristaltic pump, where any information regarding the blood is not specific. The experimental results indicate that the present method can quantify dynamic blood flow consistently, where hematocrit changes continuously over time.


2021 ◽  
Vol 12 ◽  
Author(s):  
M G Vossen ◽  
S Pferschy ◽  
C Milacek ◽  
M Haidinger ◽  
Mario Karolyi ◽  
...  

Background: Elimination of a drug during renal replacement therapy is not only dependent on flow rates, molecular size and protein binding, but is often influenced by difficult to predict drug membrane interactions. In vitro models allow for extensive profiling of drug clearance using a wide array of hemofilters and flow rates. We present a bovine blood based in vitro pharmacokinetic model for intermittent renal replacement therapy.Methods: Four different drugs were analyzed: gentamicin, doripenem, vancomicin and teicoplanin. The investigated drug was added to a bovine blood reservoir connected to a hemodialysis circuit. In total seven hemofilter models were analyzed using commonly employed flow rates. Pre-filter, post-filter and dialysate samples were drawn, plasmaseparated and analyzed using turbidimetric assays or HPLC. Protein binding of doripenem and vancomycin was measured in bovine plasma and compared to previously published values for human plasma.Results: Clearance values were heavily impacted by choice of membrane material and surface as well as by dialysis parameters such as blood flow rate. Gentamicin clearance ranged from a minimum of 90.12 ml/min in a Baxter CAHP-170 diacetate hemofilter up to a maximum of 187.90 ml/min in a Fresenius medical company Fx80 polysulfone model (blood flow rate 400 ml/min, dialysate flow rate 800 ml/min). Clearance of Gentamicin vs Vancomicin over the F80s hemofilter model using the same flow rates was 137.62 mL vs 103.25 ml/min. Doripenem clearance with the Fx80 was 141.25 ml/min.Conclusion: Clearance values corresponded very well to previously published data from clinical pharmacokinetic trials. In conjunction with in silico pharmacometric models. This model will allow precise dosing recommendations without the need of large scale clinical trials.


2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
P Mason McClatchey

Introduction: Impaired tissue oxygenation is observed in many disease states including congestive heart failure, diabetes, cancer and aging. Decreased tissue perfusion and heterogeneous distribution of blood flow in the microvasculature contributes to this pathology. The physiological mechanisms regulating homogeneity/heterogeneity of microvascular perfusion are presently unknown. We hypothesized that microfluidic properties of the glycocalyx would promote perfusion homogeneity. Methods: To test our hypothesis, we used established empirical formulations for modelling blood viscosity in vivo (blood vessels) and in vitro (glass tubes). We first assess distribution of blood flow in idealized arteriolar networks. We next simulated distribution of blood flow at an idealized capillary bifurcation. Finally, we simulated velocity profiles and pressure gradients within the vessel lumen with varying glycocalyx properties using a computational fluid dynamics approach. Results: We found that transit time heterogeneity (as assessed by STD to mean ratio) was increased approximately 9x (6.9x-10.6x) using in vitro formulations of blood viscosity relative to in vivo formulations. This effect was mathematically accounted for by increased effective blood viscosity in smaller arterioles. We also found that distribution of blood flow at an idealized microvascular bifurcation was more symmetric using the in vivo formulation than the in vitro formulation (approximately 2x greater disparity between flow in downstream vessels). This effect was mathematically accounted for by an increased hematocrit dependence of blood viscosity. Both the diameter- and hematocrit-based changes in blood viscosity were entirely predictable from fluid dynamics simulations incorporating a space-filling, semi-permeable glycocalyx layer. Summary: Our simulations indicate that the mechanical properties of the endothelial glycocalyx promote homogeneous microvascular perfusion. Conclusions: The literature provides evidence of both glycocalyx degradation and impaired tissue perfusion in the same disease states. Preservation or restoration of normal glycocalyx properties may be a viable strategy for improving tissue perfusion in a wide variety of diseases.


2011 ◽  
pp. 55-62
Author(s):  
James R. Munis

What does right atrial pressure (PRA) do to cardiac output (CO)? On the one hand, we've been taught that PRA represents preload for the right ventricle. That is, the higher the PRA, the greater the right ventricular output (and, therefore, CO). This is simply an application of Starling's law to the right side of the heart. On the other hand, we've been taught that PRA represents the downstream impedance to venous return (VR) from the periphery. That is, the higher the PRA, the lower the VR, and therefore, the lower the CO. The point of intersection between the 2 curves defines a unique blood flow rate, which is both CO and VR at the same time.


Sensors ◽  
2020 ◽  
Vol 20 (5) ◽  
pp. 1451
Author(s):  
Martin Elenkov ◽  
Paul Ecker ◽  
Benjamin Lukitsch ◽  
Christoph Janeczek ◽  
Michael Harasek ◽  
...  

Blood pumps have found applications in heart support devices, oxygenators, and dialysis systems, among others. Often, there is no room for sensors, or the sensors are simply unreliable when long-term operation is required. However, control systems rely on those hard-to-measure parameters, such as blood flow rate and pressure difference, thus their estimation takes a central role in the development process of such medical devices. The viscosity of the blood not only influences the estimation of those parameters but is often a parameter that is of great interest to both doctors and engineers. In this work, estimation methods for blood flow rate, pressure difference, and viscosity are presented using Gaussian process regression models. Different water–glycerol mixtures were used to model blood. Data was collected from a custom-built blood pump, designed for intracorporeal oxygenators in an in vitro test circuit. The estimation was performed from motor current and motor speed measurements and its accuracy was measured for: blood flow rate r2 = 0.98, root mean squared error (RMSE) = 46 mL.min−1; pressure difference r2 = 0.98, RMSE = 8.7 mmHg; and viscosity r2 = 0.98, RMSE = 0.049 mPa.s. The results suggest that the presented methods can be used to accurately predict blood flow rate, pressure, and viscosity online.


1986 ◽  
Vol 60 (1) ◽  
pp. 327-334 ◽  
Author(s):  
L. Gamas ◽  
J. S. Lee

The injection of plasma, saline, or erythrocyte (RBC) concentrate into the pulmonary circulation produces a change in the gravimetric density of the blood outflow similar to the dilution curve of dye. We used an improved density-measuring system to assess the flow of these density indicators through the lung in vivo and in vitro perfused dog lobe. From the in vitro density-dilution curves of plasma and RBC concentrate we calculated the pulmonary flow rate and found it to be 1.04 +/- 0.02 (SD) times the measured one. The outflow-dilution curves of gravimetric density were not as broad as those of optical density following in vivo injection of plasma bolus containing indocyanine green, and the gravimetric measurements dipped to base line, whereas the optical measurement did not. The density-dilution curves of isotonic saline injection are similar to that of plasma. Following injection of RBC concentrates with the dye, density changes in the pulmonary outflow lag behind the emergence of the dye. This was presumably related to RBC aggregation in the concentrates. In reference to the injected plasma, no loss in the density indicators for saline and RBC injection was observed. Based on these results and the similarity of the density indicators to the blood, we conclude that the plasma and isotonic saline are good density indicators to be used for the determination of pulmonary blood flows.


Perfusion ◽  
1996 ◽  
Vol 11 (1) ◽  
pp. 61-70 ◽  
Author(s):  
Philip D Beckley ◽  
Susan M Morris ◽  
James J Smith ◽  
Jerri L McNamara ◽  
Julie A Novak

With continuous enhancement in oxygenator design, the question is raised as to how these changes actually impact the performance of the oxygenator. The recent addition of two new oxygenators by the Bentley Division of Baxter Healthcare Corporation provided us with a unique opportunity to compare the performance of each device and isolate the impact of each design change on performance. While the basic design and flow patterns have remained the same, application of the Duraflo® II treatment has produced the Univox® Gold™ and a change in the fibre-winding technique has produced the SpiralGold™. This study compared the effects of heparin coating (Univox® to Univox® Gold™) and fibre-winding (Univox® Gold™ to SpiralGold™) on gas and heat transfer and resistance to blood flow (pressure drop). Six oxygenators of each model were evaluated utilizing an in vitro single pass circuit, which first conditioned bovine blood to the Association for the Advancement of Medical Instrumentation (AAMI) venous standards. Blood flows of 4.0, 5.0, 6.0 and 7.0 I/min, FiO2 values of 1.0, 0.8 and 0.6, and gas-to-blood flow ratios of 0.5, 1.0 and 1.5 were chosen as test variables. Data generated included oxygen transfer, carbon dioxide transfer, arterial pO2, resistance to blood flow, and coefficient of heat exchange. The results indicate that the Duraflo II treatment does not have a significant effect on gas and heat transfer or resistance to blood flow. The fibre-winding technique employed with the new SpiralGold™, however, has improved significantly gas exchange and arterial PO2 when compared with the previous Univox® models. Resistance to blood flow and coefficient of heat exchange were not affected significantly by the winding technique.


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