Experimental Investigation of Air Compliance Effect on Measurement of Mechanical Properties of Blood Sample Flowing in Microfluidic Channels

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.

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

Micromachines ◽

10.3390/mi10090577 ◽

2019 ◽

Vol 10 (9) ◽

pp. 577 ◽

Cited By ~ 4

Author(s):

Yang Jun Kang

Keyword(s):

Blood Flow ◽

Shear Rate ◽

Microfluidic Device ◽

Blood Viscosity ◽

Blood Samples ◽

Image Intensity ◽

Blood Flows ◽

Pressure Index ◽

Sequential Measurement ◽

Rbc Aggregation

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.

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Ultrasound Standing Wave-Based Cell-to-liquid Separation for Measuring Viscosity and Aggregation of Blood Sample

Sensors ◽

10.3390/s20082284 ◽

2020 ◽

Vol 20 (8) ◽

pp. 2284

Author(s):

Gwangho Kim ◽

Sanghwa Jeong ◽

Yang Jun Kang

Keyword(s):

Mechanical Properties ◽

Blood Sample ◽

Present Method ◽

Ex Vivo ◽

Ultrasonic Transducer ◽

Excitation Frequency ◽

Periodic Pattern ◽

Blood Samples ◽

Rbc Aggregation ◽

Dextran Solution

When quantifying mechanical properties of blood samples flowing in closed fluidic circuits, blood samples are collected at specific intervals. Centrifugal separation is considered as a required procedure for preparing blood samples. However, the use of centrifuge is associated with several issues, including the potential for red blood cell (RBC) lysis, clotting activation, and RBC adhesions in the tube. In this study, an ultrasonic transducer is employed to separate RBCs or diluent from blood sample. The ultrasonic radiation force is much smaller than the centrifugal force acting in centrifuge, it can avoid critical issues occurring under centrifuge. Then, the RBC aggregation and blood viscosity of the blood sample are obtained using the microfluidic technique. According to the numerical results, ultrasonic transducers exhibited a maximum quality factor at an excitation frequency of 2.1 MHz. Periodic pattern of acoustic pressure fields were visualized experimentally as a column mode. The half wavelength obtained was as 0.5 λ = 0.378 ± 0.07 mm. The experimental results agreed with the analytical estimation sufficiently. An acoustic power of 2 W was selected carefully for separating RBCs or diluent from various blood samples (i.e., Hct = 20% ~ 50%; diluent: plasma, 1x phosphate-buffered saline (PBS), and dextran solution). The present method was employed to separate fixed blood samples which tended to stack inside the tube while using the centrifuge. Fixed RBCs were collected easily with an ultrasonic transducer. After various fixed blood samples with different base solutions (i.e., glutaraldehyde solution, 1x PBS, and dextran solution) were prepared using the present method, RBC aggregation and the viscosity of the blood sample are successfully obtained. In the near future, the present method will be integrated into ex vivo or in vitro fluidic circuit for measuring multiple mechanical properties of blood samples for a certain longer period.

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Microfluidic-Based Biosensor for Blood Viscosity and Erythrocyte Sedimentation Rate Using Disposable Fluid Delivery System

Micromachines ◽

10.3390/mi11020215 ◽

2020 ◽

Vol 11 (2) ◽

pp. 215

Author(s):

Yang Jun Kang

Keyword(s):

Blood Sample ◽

Erythrocyte Sedimentation Rate ◽

Flow Rate ◽

Sedimentation Rate ◽

Blood Viscosity ◽

Blood Samples ◽

Image Intensity ◽

Fluid Delivery ◽

Erythrocyte Sedimentation ◽

Over Time

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.

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

Micromachines ◽

10.3390/mi9090467 ◽

2018 ◽

Vol 9 (9) ◽

pp. 467 ◽

Cited By ~ 8

Author(s):

Yang Kang

Keyword(s):

Blood Flow ◽

Blood Viscosity ◽

Blood Flow Rate ◽

Aggregation Index ◽

Simple Method ◽

Blood Flows ◽

Wide Channel ◽

Rbc Aggregation ◽

The Right

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.

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Impact of Trail Running Races on Blood Viscosity and Its Determinants: Effects of Distance

International Journal of Molecular Sciences ◽

10.3390/ijms21228531 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8531

Author(s):

Mélanie Robert ◽

Emeric Stauffer ◽

Elie Nader ◽

Sarah Skinner ◽

Camille Boisson ◽

...

Keyword(s):

Blood Viscosity ◽

Blood Rheology ◽

Tissue Perfusion ◽

Aerobic Performance ◽

Free Hemoglobin ◽

Blood Samples ◽

Shear Rates ◽

Before And After ◽

Rbc Aggregation ◽

Trail Running

Blood rheology is a key determinant of tissue perfusion at rest and during exercise. The present study investigated the effects of race distance on hematological, blood rheological, and red blood cell (RBC) senescence parameters. Eleven runners participated in the Martigny–Combes à Chamonix 40 km race (MCC, elevation gain: 2300 m) and 12 others in the Ultra-Trail du Mont Blanc (UTMB, 171 km, elevation gain: 10,000 m). Blood samples were collected before and after the races. After the UTMB, the percentage of RBC phosphatidylserine (PS) exposure was not affected while RBC CD235a levels decreased and RBC-derived microparticles increased. In contrast, after the MCC, RBC PS exposure increased, while RBC CD235a and RBC-derived microparticles levels were not affected. The free hemoglobin and hemolysis rate did not change during the races. RBC aggregation and blood viscosity at moderate shear rates increased after the MCC. RBC deformability, blood viscosity at a high shear rate, and hematocrit decreased after the UTMB but not after the MCC. Our results indicate that blood rheology behavior is different between a 40 km and a 171 km mountain race. The low blood viscosity after the ultra-marathon might facilitate blood flow to the muscles and optimize aerobic performance.

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Blood Viscoelasticity Measurement Using Interface Variations in Coflowing Streams under Pulsatile Blood Flows

Micromachines ◽

10.3390/mi11030245 ◽

2020 ◽

Vol 11 (3) ◽

pp. 245 ◽

Cited By ~ 1

Author(s):

Yang Jun Kang

Keyword(s):

Blood Sample ◽

Flow Rate ◽

Present Method ◽

Experimental Results ◽

Blood Samples ◽

Constant Flow Rate ◽

Blood Flows ◽

The Status ◽

Sinusoidal Flow ◽

Linear Differential

Blood flows in microcirculation are determined by the mechanical properties of blood samples, which have been used to screen the status or progress of diseases. To achieve this, it is necessary to measure the viscoelasticity of blood samples under a pulsatile blood condition. In this study, viscoelasticity measurement is demonstrated by quantifying interface variations in coflowing streams. To demonstrate the present method, a T-shaped microfluidic device is designed to have two inlets (a, b), one outlet (a), two guiding channels (blood sample channel, reference fluid channel), and one coflowing channel. Two syringe pumps are employed to infuse a blood sample at a sinusoidal flow rate. The reference fluid is supplied at a constant flow rate. Using a discrete fluidic circuit model, a first-order linear differential equation for the interface is derived by including two approximate factors (F1 = 1.094, F2 = 1.1087). The viscosity and compliance are derived analytically as viscoelasticity. The experimental results showed that compliance is influenced substantially by the period. The hematocrit and diluent contributed to the varying viscosity and compliance. The viscoelasticity varied substantially for red blood cells fixed with higher concentrations of glutaraldehyde solution. The experimental results showed that the present method has the ability to monitor the viscoelasticity of blood samples under a sinusoidal flow-rate pattern.

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Development of a blood sample detector for multi-tracer positron emission tomography using gamma spectroscopy

EJNMMI Physics ◽

10.1186/s40658-019-0263-x ◽

2019 ◽

Vol 6 (1) ◽

Cited By ~ 1

Author(s):

Carlos Velasco ◽

Adriana Mota-Cobián ◽

Jesús Mateo ◽

Samuel España

Keyword(s):

Positron Emission Tomography ◽

Blood Sample ◽

Pet Imaging ◽

Spectroscopic Analysis ◽

Gamma Spectroscopy ◽

Emission Tomography ◽

Blood Samples ◽

Positron Emission

Abstract Background Multi-tracer positron emission tomography (PET) imaging can be accomplished by applying multi-tracer compartment modeling. Recently, a method has been proposed in which the arterial input functions (AIFs) of the multi-tracer PET scan are explicitly derived. For that purpose, a gamma spectroscopic analysis is performed on blood samples manually withdrawn from the patient when at least one of the co-injected tracers is based on a non-pure positron emitter. Alternatively, these blood samples required for the spectroscopic analysis may be obtained and analyzed on site by an automated detection device, thus minimizing analysis time and radiation exposure of the operating personnel. In this work, a new automated blood sample detector based on silicon photomultipliers (SiPMs) for single- and multi-tracer PET imaging is presented, characterized, and tested in vitro and in vivo. Results The detector presented in this work stores and analyzes on-the-fly single and coincidence detected events. A sensitivity of 22.6 cps/(kBq/mL) and 1.7 cps/(kBq/mL) was obtained for single and coincidence events respectively. An energy resolution of 35% full-width-half-maximum (FWHM) at 511 keV and a minimum detectable activity of 0.30 ± 0.08 kBq/mL in single mode were obtained. The in vivo AIFs obtained with the detector show an excellent Pearson’s correlation (r = 0.996, p < 0.0001) with the ones obtained from well counter analysis of discrete blood samples. Moreover, in vitro experiments demonstrate the capability of the detector to apply the gamma spectroscopic analysis on a mixture of 68Ga and 18F and separate the individual signal emitted from each one. Conclusions Characterization and in vivo evaluation under realistic experimental conditions showed that the detector proposed in this work offers excellent sensibility and stability. The device also showed to successfully separate individual signals emitted from a mixture of radioisotopes. Therefore, the blood sample detector presented in this study allows fully automatic AIFs measurements during single- and multi-tracer PET studies.

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Microsphere-Based Microfluidic Device for Plasma Separation and Potential Biochemistry Analysis Applications

Micromachines ◽

10.3390/mi12050487 ◽

2021 ◽

Vol 12 (5) ◽

pp. 487

Author(s):

Hongyan Xu ◽

Zhangying Wu ◽

Jinan Deng ◽

Jun Qiu ◽

Ning Hu ◽

...

Keyword(s):

Blood Sample ◽

Microfluidic Device ◽

Biochemical Analysis ◽

Cost Effective ◽

Clinical Diagnostics ◽

Correction Factors ◽

Separation Device ◽

Blood Samples ◽

Plasma Separation ◽

Blood Biochemical

The development of a simple, portable, and cost-effective plasma separation platform for blood biochemical analysis is of great interest in clinical diagnostics. We represent a plasma separation microfluidic device using microspheres with different sizes as the separation barrier. This plasma separation device, with 18 capillary microchannels, can extract about 3 μL of plasma from a 50 μL blood sample in about 55 min. The effects of evaporation and the microsphere barrier on the plasma biochemical analysis results were studied. Correction factors were applied to compensate for these two effects. The feasibility of the device in plasma biochemical analysis was validated with clinical blood samples.

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Quantitative Monitoring of Dynamic Blood Flows Using Coflowing Laminar Streams in a Sensorless Approach

Applied Sciences ◽

10.3390/app11167260 ◽

2021 ◽

Vol 11 (16) ◽

pp. 7260

Author(s):

Yang Jun Kang

Keyword(s):

Blood Flow ◽

Flow Rate ◽

Blood Viscosity ◽

Measurement Errors ◽

Present Method ◽

Test Fluid ◽

Constant Flow Rate ◽

Rbc Aggregation ◽

Sinusoidal Flow ◽

Analytical Expressions

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.

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Continuous and simultaneous measurement of the biophysical properties of blood in a microfluidic environment

The Analyst ◽

10.1039/c6an01593j ◽

2016 ◽

Vol 141 (24) ◽

pp. 6583-6597 ◽

Cited By ~ 18

Author(s):

Yang Jun Kang

Keyword(s):

Blood Viscosity ◽

Simultaneous Measurement ◽

Measurement Method ◽

Biophysical Properties ◽

Rbc Aggregation

A new measurement method is proposed to quantify blood viscosity, blood viscoelasticity, and RBC aggregation, in a continuous and simultaneous fashion.

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