scholarly journals Microfluidic-Based Biosensor for Sequential Measurement of Blood Pressure and RBC Aggregation Over Continuously Varying Blood Flows

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 (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.


Micromachines ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 460
Author(s):  
Yang Jun Kang

Air compliance has been used effectively to stabilize fluidic instability resulting from a syringe pump. It has also been employed to measure blood viscosity under constant shearing flows. However, due to a longer time delay, it is difficult to quantify the aggregation of red blood cells (RBCs) or blood viscoelasticity. To quantify the mechanical properties of blood samples (blood viscosity, RBC aggregation, and viscoelasticity) effectively, it is necessary to quantify contributions of air compliance to dynamic blood flows in microfluidic channels. In this study, the effect of air compliance on measurement of blood mechanical properties was experimentally quantified with respect to the air cavity in two driving syringes. Under periodic on–off blood flows, three mechanical properties of blood samples were sequentially obtained by quantifying microscopic image intensity (<I>) and interface (α) in a co-flowing channel. Based on a differential equation derived with a fluid circuit model, the time constant was obtained by analyzing the temporal variations of β = 1/(1–α). According to experimental results, the time constant significantly decreased by securing the air cavity in a reference fluid syringe (~0.1 mL). However, the time constant increased substantially by securing the air cavity in a blood sample syringe (~0.1 mL). Given that the air cavity in the blood sample syringe significantly contributed to delaying transient behaviors of blood flows, it hindered the quantification of RBC aggregation and blood viscoelasticity. In addition, it was impossible to obtain the viscosity and time constant when the blood flow rate was not available. Thus, to measure the three aforementioned mechanical properties of blood samples effectively, the air cavity in the blood sample syringe must be minimized (Vair, R = 0). Concerning the air cavity in the reference fluid syringe, it must be sufficiently secured about Vair, R = 0.1 mL for regulating fluidic instability because it does not affect dynamic blood flows.


2001 ◽  
Vol 95 (2) ◽  
pp. 408-415 ◽  
Author(s):  
Christian Lenz ◽  
Annette Rebel ◽  
Enrico Bucci ◽  
Klaus van Ackern ◽  
Wolfgang Kuschinsky ◽  
...  

Background The hypothesis of a compensatory dilation of cerebral vessels to maintain cerebral blood flow at a high blood viscosity was tested during hypercapnia in the study after replacement of blood by hemoglobin solutions of defined viscosities. If compensatory vasodilation exists at normocapnia at a high blood viscosity, vasodilatory mechanisms may be exhausted when hypercapnia is added, resulting in a lack of increase in cerebral blood flow at hypercapnia. Methods In conscious rats, blood was replaced by ultrapurified cross-linked hemoglobin solutions that had defined and shear rate-independent low or high viscosities (low- and high-viscosity groups). Blood viscosity differed threefold between both groups (1.2 vs. 3.6 mP x s). Thereafter, rats inhaled either a normal or an increased concentration of carbon dioxide in air. Cerebral blood flow was determined by the iodo[14C]antipyrine method. Results During normocapnia, global and local cerebral blood flows did not differ between both groups. With increasing degrees of hypercapnia, global and local cerebral blood flows were gradually elevated in the low-viscosity group (2.8 ml x mmHg(-1) CO2 x 100 g(-1) x min(-1)), whereas they remained unchanged in the high-viscosity group. Conclusions Changes in blood viscosity do not result in changes of cerebral blood flow as long as cerebral vessels can compensate for these changes by vasodilation or vasoconstriction. However, such vascular compensatory adjustments may be exhausted in their response to further pathophysiologic conditions in blood vessels that have already been dilated or constricted as a result of changes in blood viscosity.


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.


Micromachines ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 215
Author(s):  
Yang Jun Kang

To quantify the variation of red blood cells (RBCs) or plasma proteins in blood samples effectively, it is necessary to measure blood viscosity and erythrocyte sedimentation rate (ESR) simultaneously. Conventional microfluidic measurement methods require two syringe pumps to control flow rates of both fluids. In this study, instead of two syringe pumps, two air-compressed syringes (ACSs) are newly adopted for delivering blood samples and reference fluid into a T-shaped microfluidic channel. Under fluid delivery with two ACS, the flow rate of each fluid is not specified over time. To obtain velocity fields of reference fluid consistently, RBCs suspended in 40% glycerin solution (hematocrit = 7%) as the reference fluid is newly selected for avoiding RBCs sedimentation in ACS. A calibration curve is obtained by evaluating the relationship between averaged velocity obtained with micro-particle image velocimetry (μPIV) and flow rate of a syringe pump with respect to blood samples and reference fluid. By installing the ACSs horizontally, ESR is obtained by monitoring the image intensity of the blood sample. The averaged velocities of the blood sample and reference fluid (<UB>, <UR>) and the interfacial location in both fluids (αB) are obtained with μPIV and digital image processing, respectively. Blood viscosity is then measured by using a parallel co-flowing method with a correction factor. The ESR is quantified as two indices (tESR, IESR) from image intensity of blood sample (<IB>) over time. As a demonstration, the proposed method is employed to quantify contributions of hematocrit (Hct = 30%, 40%, and 50%), base solution (1× phosphate-buffered saline [PBS], plasma, and dextran solution), and hardened RBCs to blood viscosity and ESR, respectively. Experimental Results of the present method were comparable with those of the previous method. In conclusion, the proposed method has the ability to measure blood viscosity and ESR consistently, under fluid delivery of two ACSs.


1994 ◽  
Vol 267 (2) ◽  
pp. H471-H476
Author(s):  
M. Dalinghaus ◽  
H. Knoester ◽  
J. W. Gratama ◽  
J. Van der Meer ◽  
W. G. Zijlstra ◽  
...  

In chronic hypoxemia blood flow and oxygen supply to vital organs are maintained, but to nonvital organs they are decreased. We measured organ blood flows (microspheres) and whole blood viscosity in 10 chronically hypoxemic lambs, with an atrial septal defect and pulmonary stenosis, and in 8 control lambs. Vascular hindrance (resistance/viscosity) was calculated to determine to what extent the effect of increased blood viscosity on organ blood flow was compensated for by a decrease in vascular tone. Arterial oxygen saturation was decreased (68 +/- 10 vs. 91 +/- 3%, P < 0.001), and both hemoglobin concentration (145 +/- 10 vs. 109 +/- 9 g/l, P < 0.05) and blood viscosity (4.4 +/- 0.6 vs. 3.6 +/- 0.6 mPa.s, P < 0.05) were increased in hypoxemic lambs. Systemic blood flow, oxygen supply, oxygen uptake, and blood pressures were not significantly different between hypoxemic and control lambs. Myocardial and cerebral blood flow was maintained in hypoxemic lambs, whereas renal, gastrointestinal, splenic, and thyroidal blood flows were at least 30% lower. Vascular hindrance was significantly decreased in the myocardium and tended to be lower in the brain of hypoxemic lambs, but in all other organs it was similar to that in control lambs. It is concluded that blood flow is redistributed in chronic hypoxemia in lambs; myocardial and cerebral blood flow is maintained, whereas blood flow to splanchnic organs, the kidneys, and the thyroids is decreased. The decreased blood flow to organs is a consequence of the increased whole blood viscosity.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1518-1518
Author(s):  
Tamas Alexy ◽  
Thomas D. Coates ◽  
John C Wood ◽  
Herbert J. Meiselman ◽  
Rosalinda B Wenby ◽  
...  

Abstract Abstract 1518 Poster Board I-541 Introduction Chronic blood transfusions are commonly used as therapy for sickle cell disease (SCD, HbSS) in order to improve oxygen delivery and minimize complications such as stroke in high-risk children. Vaso-occlusive crises can occur in regions of high shear flow (e.g., major cerebral artery occlusions) or regions of low shear flow (e.g., marrow infarct) leading to acute ischemia and, if severe, to necrosis of affected tissues. Transfusion with normal (AA) RBC causes an increase of hematocrit (H) that is complicated by two opposing factors: increased hematocrit (H) causes a linear increase of oxygen carrying capacity and also an exponential increase of blood viscosity (η). As a consequence, the calculated oxygen transport effectiveness, defined as the ratio of H to η (H/η), is a biphasic function of hematocrit: H/η initially increases with H, reaches a maximum at an optimal H value, and then declines with further increases of H. At equal H and shear rate, sickle (SS) blood has significantly higher viscosity than AA and hence part of the strategy for transfusing SCD patients is to reduce η so as to improve H/η. Viscosity studies at high shear rates indicate that an optimum H can be demonstrated for AA-SS RBC mixtures prepared by adding AA RBC to SS blood to simulate transfusion. In marked contrast, low shear rate results for AA-SS mixtures indicate that there is no optimum hematocrit and H/η always decreases with increasing H (Transfusion 46:912-918, 2006). In order to extend these previous in vitro observations to SCD patients, we have measured blood viscosity and hematocrit using whole blood samples acquired prior to and following routine therapeutic transfusion; H/η was calculated over a wide, physiologically relevant shear rate range. Methods All subjects (n= 8, mean age =18.7 years) had homozygous HbSS disease, were crisis-free for > 4 weeks, and were enrolled in a chronic transfusion protocol designed to yield < 30% HbS and a post-transfusion H of 30-35%. Blood samples were obtained pre- and within 120 hours post-transfusion. A computer-controller tube viscometer was used to determine blood viscosity (37 °C, 40 mm Hg oxygen tension) over a shear rate range of 1 – 1,000 1/s. Results 1) As anticipated, blood viscosity and the degree of non-Newtonian flow behavior increased with H (24.7% pre-transfusion, 34.6% post-transfusion); 2) the change of H/η from pre- to post- transfusion was markedly affected by shear rate (Figure). As indicated, there is a large adverse effect at low shear (i.e., H/η reduced by 20-25% following transfusion), a neutral effect at about 50-100 1/s, and an improved H/η at high shear (Figure). That is, transfusion with AA RBC to obtain a lower percent SS RBC and a higher H actually impairs oxygen transport effectiveness at low shear and is only beneficial at high shear. Conclusions Clinical experience suggests that transfusion regimens aimed a keeping HbS at 30-50% are effective in preventing recurrent strokes in high-risk children. However, our new in vivo transfusion data suggest that at low shear rates, %HbS must be reduced further for H/η to surpass pre-transfusion levels. We interpret these findings as being consistent with our previous data for AA-SS RBC mixtures. They are also consistent with clinical results indicating lack of efficacy for transfusion in low flow areas (e.g., bone marrow during acute crisis) but highly beneficial effects in high flow regions (e.g., cerebral arteries). Our results thus suggest that benefits of transfusion may vary depending on local flow rates (i.e., shear rates) and organ-specific hemodynamics. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1001-1001
Author(s):  
Jon Detterich ◽  
Adam M Bush ◽  
Roberta Miyeko Kato ◽  
Rose Wenby ◽  
Thomas D. Coates ◽  
...  

Abstract Abstract 1001 Introduction: SCT occurs in 8% of African Americans and is not commonly associated with clinical disease. Nonetheless, the United States Armed Forces has reported that SCT conveys a 30-fold risk of sudden cardiac arrest and a 200-fold risk from exertional rhabdomyolysis. In fact, rhabdomyolysis in athletes with SCT has been the principal cause of death in NCAA football players in the last decade, leading to recently mandated SCT testing in all Division-1 players. In SCT, RBC sickle only under extreme conditions and with slow kinetics. Therefore, rhabdomyolysis most likely occurs in SCT when a “perfect storm” of factors converges to critically imbalance oxygen supply and demand in muscles. We hypothesize that in SCT subjects, abnormal RBC rheology, particularly aggregation and deformability, play an important role in abnormal muscle blood flow supply and distribution to exercising muscle. To test this hypothesis, we examined whole blood viscosity, RBC aggregation, and RBC deformability in 11 SCT and 10 control subjects prior to and following maximum handgrip exercise. Methods: Maximum voluntary contraction (MVC) was assessed by handgrip dynamometer in the dominant arm. Baseline blood was collected for CBC, whole blood viscosity, RBC aggregation, and RBC deformability. Patients then maintained 60% MVC exercise until exhaustion. Following 8 minutes of recovery, a venous blood gas and blood for repeat viscosity assessments was collected from the antecubital fossa of the exercising limb. Whole blood viscosity over a shear rate range of 1–1, 000 1/s was determined by an automated tube viscometer, RBC deformability from 0.5–50 Pa via laser ektacytometry (LORCA) and RBC aggregation in both autologous plasma and 3% dextran 70 kDa using an automated cone-place aggregometer (Myrenne). Aggregation measurements included extent at stasis (M), strength of aggregation (GT min) and kinetics (T ½). Results: Baseline CBC and aggregation values are summarized in Table 1. Both static RBC aggregation in plasma and RBC aggregation in dextran (aggregability) were significantly increased in SCT (Table 1). The rate of aggregation formation trended higher in SCT but the strength of aggregation was not different between the two groups. In SCT subjects, red cell deformability was impaired at low shear stress but greater than controls at higher shear stress (Figure 1). Red cell deformability was completely independent of oxygenation status states in both SCT and control subjects. Whole blood viscosity did not different between the two groups whether oxygenated or deoxygenated and prior to or following handgrip exercise. Discussion: Three important hemorheological differences were observed for SCT subjects versus controls: a) RBC deformability was below control at low stress levels yet greater than control at higher stress; b) The extent of RBC aggregation in autologous plasma was about 40% greater; c) The extent of RBC aggregation for washed RBC re-suspended in an aggregating medium (i.e., 3% dextran 70 kDa) was about 30% higher. RBC deformability is a major determinant of in vivo blood flow dynamics, especially in the microcirculation; decreased deformability adversely affects tissue perfusion. RBC aggregation is also an important determinant since it affects both resistance to blood flow and RBC distribution in a vascular bed (e.g., plasma skimming). The finding of greater aggregability (i.e., higher aggregation in the defined dextran medium) indicates that RBC in SCT have an altered membrane surface in which the penetration of this polymer into the glycocalyx is abnormal. The combined effects of these three rheological parameters is likely to impair in vivo blood flow in SCT, perhaps to a degree resulting in pathophysiological changes of the cardiovascular system. Disclosures: Coates: Novartis: Speakers Bureau; Apopharma: Consultancy. Wood:Ferrokin Biosciences: Consultancy; Shire: Consultancy; Apotex: Consultancy, Honoraria; Novartis: Honoraria, Research Funding.


Author(s):  
R. Mehri ◽  
C. Mavriplis ◽  
M. Fenech

The purpose of the work presented this paper is to design a model to study experimentally and numerically a micro-Couette blood flow to obtain a constant and controlled shear rate that is a suitable environment for analysis of Red Blood Cell (RBC) aggregation. Due to the simplicity of the flow conditions, aggregate size can be related to the constant shear rate applied. This Couette flow is created by the motion of a second fluid that entrains the blood. The experimental work is coupled with 3D numerical simulations performed using a research computational fluid dynamics solver, Nek5000, based on the spectral element method, while the experiments are conducted using a micro-particle image velocimetry system. Two models of microchannels, with different dimensions, 150 × 33μm and 170 × 64μm, are fabricated in the laboratory using standard photolithography methods. The design of the channel is based on several parameters determined by the simulations. A Newtonian model is tested numerically and experimentally. Blood is then tested experimentally to be compared to the simulation results. We find that using a velocity ratio of 4 between the two Newtonian fluids, we create a flow where one third of the channel thickness is filled with the fluid destined to be blood. In the blood experiments, the velocity profile in this layer is approximately linear, resulting in the desired controlled conditions for the study of RBC aggregation.


1986 ◽  
Vol 64 (10) ◽  
pp. 1310-1315 ◽  
Author(s):  
F. J. Burczynski ◽  
C. V. Greenway

Experiments were carried out to determine the accuracy and validity of estimations of hepatic blood flow from clearance data during infusions of galactose in anesthetized cats. Clearance calculations were compared directly with the measured hepatic blood flows using a hepatic venous long-circuit technique. This technique allowed direct measurement and alteration of hepatic blood flow and collection of arterial and mixed hepatic venous blood samples without depletion of the animal's blood volume. It was found that infusions of galactose could not be used to estimate accurately hepatic blood flow. Infusion rate could not be used as an estimate of hepatic or splanchnic uptake owing to substantial and variable extrasplanchnic uptake. As a result, estimated hepatic flows allowing for incomplete extraction overestimated the true flow. On the other hand, extraction was less than 100%. This caused systemic galactose clearance to underestimate hepatic blood flow. These errors could cancel each other giving an apparently good estimate of hepatic flow from systemic galactose clearance. This agreement was fortuitous and occurred only at a specific dose and blood flow. We conclude that in the absence of independent measurements of both extrasplanchnic uptake and splanchnic extraction of galactose, systemic galactose clearance is not a reliable measure of hepatic blood flow in anesthetized cats. Until proved otherwise, it seems likely that this is also true in humans.


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