High-Throughput and Label-Free Blood-on-a-Chip for Malaria Diagnosis

2017

Sensors

Red blood cell (RBC) aggregation and erythrocyte sedimentation rate (ESR) are considered to be promising biomarkers for effectively monitoring blood rheology at extremely low shear rates. In this study, a microfluidic-based measurement technique is suggested to evaluate RBC aggregation under hematocrit variations due to the continuous ESR. After the pipette tip is tightly fitted into an inlet port, a disposable suction pump is connected to the outlet port through a polyethylene tube. After dropping blood (approximately 0.2 mL) into the pipette tip, the blood flow can be started and stopped by periodically operating a pinch valve. To evaluate variations in RBC aggregation due to the continuous ESR, an EAI (Erythrocyte-sedimentation-rate Aggregation Index) is newly suggested, which uses temporal variations of image intensity. To demonstrate the proposed method, the dynamic characterization of the disposable suction pump is first quantitatively measured by varying the hematocrit levels and cavity volume of the suction pump. Next, variations in RBC aggregation and ESR are quantified by varying the hematocrit levels. The conventional aggregation index (AI) is maintained constant, unrelated to the hematocrit values. However, the EAI significantly decreased with respect to the hematocrit values. Thus, the EAI is more effective than the AI for monitoring variations in RBC aggregation due to the ESR. Lastly, the proposed method is employed to detect aggregated blood and thermally-induced blood. The EAI gradually increased as the concentration of a dextran solution increased. In addition, the EAI significantly decreased for thermally-induced blood. From this experimental demonstration, the proposed method is able to effectively measure variations in RBC aggregation due to continuous hematocrit variations, especially by quantifying the EAI.

Section: Introductionmentioning

confidence: 99%

Microfluidic-Based Measurement Method of Red Blood Cell Aggregation under Hematocrit Variations

2017

Sensors

“…While the blood is delivered into micropillars under a constant flow rate, the deformability of RBCs is evaluated by analyzing the temporal variations of blood velocity or image intensity for a specific duration. 20,21 The previous method could provide high throughput and precise detection of minor differences in subpopulations. However, the previous method is applied to quantify the RBC deformability and blood viscosity, especially under a constant blood flow condition.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous measurement of erythrocyte deformability and blood viscoelasticity using micropillars and co-flowing streams under pulsatile blood flows

2017

Biomicrofluidics

Self Cite

The biophysical properties of blood provide useful information on the variation in hematological disorders or diseases. In this study, a simultaneous measurement method of RBC (Red Blood Cell) deformability and blood viscoelasticity is proposed by evaluating hemodynamic variations through micropillars and coflowing streams under sinusoidal blood flow. A disposable microfluidic device is composed of two inlets and two outlets, two upper side channels, and two lower side channels connected to one bridge channel. First, to measure the RBC deformability, the left-lower side channel has a deformability assessment chamber (DAC) with narrow-sized micropillars. Second, to evaluate the blood viscoelasticity in co-flowing streams, a phosphate buffered saline solution is supplied at a constant flow rate. By closing or opening a pinch valve connected to the outlet of DAC, blood flows in forward or back-and-forth mode. A time-resolved micro-particle image velocimetry technique and a digital image processing technique are used to quantify the blood velocity and image intensity. Then, RBC deformability is evaluated by quantifying the blood volume passing through the DAC under forward flow, and quantifying the variations of blood velocity and image intensity in the DAC under back-and-forth flow. Using a discrete circuit model, blood viscoelasticity is obtained by evaluating variations of blood velocity and co-flowing streams. The effect of several factors (period, hematocrit, and base solution) on the performance is quantitatively evaluated. Based on the experimental results, the period of sinusoidal flow and hematocrit are fixed at 30 s and 50%, respectively. As a performance demonstration, the proposed method is employed to detect the homogeneous and heterogeneous blood composed of normal RBCs and hardened RBCs. These experimental results show that the RBC deformability is more effective to detect minor subpopulations of heterogeneous bloods, compared with blood viscoelasticity. Therefore, it leads to the conclusion that the proposed method has the ability to evaluate RBC deformability and blood viscoelasticity under sinusoidal blood flow, with sufficient accuracy and highthroughput. Published by AIP Publishing. [http://dx

“…Using the same pressure drop for each channel (ΔP = R PBS × Q PBS = R Blood × Q Blood ), the fluidic resistance ratio of the blood channel to the PBS channel (R Blood /R PBS ) is expressed as R Blood /R PBS = Q PBS /Q Blood . For a rectangular channel with a lower aspect ratio (AR = depth/width = 100/2000), the fluidic resistance for each channel can be approximately expressed as R = 12 × µ × l/(w × h 3 ), as explained in previous work [ 43 ]. Because each fluid channel has identical dimensions of channel depth (h) and length (l), an analytical formula for blood viscosity (µ Blood ) can be simply derived as [ 43 ]:

…”

Section: Methodsmentioning

confidence: 99%

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

2018

Micromachines

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 () and the RBCs disaggregated in the right channel (), the RBC aggregation index (AIPM) is obtained by dividing by . 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.