<i>In vitro</i>and<i>ex vivo</i>measurement of the biophysical properties of blood using microfluidic platforms and animal models

Kang, Yang Jun; Lee, Sang Joon

doi:10.1039/c8an00231b

Cited by 42 publications

(34 citation statements)

References 135 publications

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“…The previous study has reported that biophysical properties of blood samples (hematocrit (Hct), viscosity, and erythrocyte sedimentation rate (ESR)) are strongly correlated with coronary heart diseases [3]. Thereafter, the biophysical properties of the blood sample have been studied extensively for the effective monitoring of circulatory disorders [4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

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

Kang

2020

Micromachines

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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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Section: Introductionmentioning

confidence: 99%

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

Kang

2020

Micromachines

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“…Therefore, microfluidic devices that mimic vessel branching, shortening, and compression coupled with a simple image analysis algorithm address this issue and provide a simple solution to accurately model flow through the microvasculature . Multiple studies have investigated the combined use of microfluidic techniques with RBC image analysis to assess cell deformability, but these systems focus on either single microchannels with low cell throughput or wide channels that measure bulk cell properties. Furthermore, these studies are limited due to the inability to accurately detect cell edges within microchannels that constrict individual cells.…”

Section: Introductionmentioning

confidence: 99%

Integrated automated particle tracking microfluidic enables high‐throughput cell deformability cytometry for red cell disorders

et al. 2018

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Investigating individual red blood cells (RBCs) is critical to understanding hematologic diseases, as pathology often originates at the single-cell level. Many RBC disorders manifest in altered biophysical properties, such as deformability of RBCs. Due to limitations in current biophysical assays, there exists a need for high-throughput analysis of RBC deformability with single-cell resolution. To that end, we present a method that pairs a simple in vitro artificial microvasculature network system with an innovative MATLAB-based automated particle tracking program, allowing for high-throughput, single-cell deformability index (sDI) measurements of entire RBC populations. We apply our technology to quantify the sDI of RBCs from healthy volunteers, Sickle cell disease (SCD) patients, a transfusion-dependent beta thalassemia major patient, and in stored packed RBCs (pRBCs) that undergo storage lesion over 4 weeks. Moreover, our system can also measure cell size for each RBC, thereby enabling 2D analysis of cell deformability vs cell size with single cell resolution akin to flow cytometry. Our results demonstrate the clear existence of distinct biophysical RBC subpopulations with high interpatient variability in SCD as indicated by large magnitude skewness and kurtosis values of distribution, the "shifting" of sDI vs RBC size curves over transfusion cycles in beta thalassemia, and the appearance of low sDI RBC subpopulations within 4 days of pRBC storage. Overall, our system offers an inexpensive, convenient, and high-throughput method to gauge single RBC deformability and size for any RBC population and has the potential to aid in disease monitoring and transfusion guidelines for various RBC disorders.

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“…Microfluidics enables creating fluidic structures at the same scale as even the smallest blood vessels . Various microfluidic designs have been developed to interpret RBCs deformability . In some designs, transit of a single RBC through a channel slightly larger and wider than cell diameter is quantified, and deformability is inferred from the geometric shape of the transiting RBC .…”

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Development of a flow standard to enable highly reproducible measurements of deformability of stored red blood cells in a microfluidic device

et al. 2020

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BACKGROUND: Great deformability allows red blood cells (RBCs) to flow through narrow capillaries in tissues. A number of microfluidic devices with capillary-like microchannels have been developed to monitor storagerelated impairment of RBC deformability during blood banking operations. This proof-of-concept study describes a new method to standardize and improve reproducibility of the RBC deformability measurements using one of these devices.STUDY DESIGN AND METHODS: The rate of RBC flow through the microfluidic capillary network of the microvascular analyzer (MVA) device made of polydimethylsiloxane was measured to assess RBC deformability. A suspension of microbeads in a solution of glycerol in phosphate-buffered saline was developed to be used as an internal flow rate reference alongside RBC samples in the same device. RBC deformability and other in vitro quality markers were assessed weekly in six leukoreduced RBC concentrates (RCCs) dispersed in saline-adenine-glucose-mannitol additive solution and stored over 42 days at 4°C. RESULTS:The use of flow reference reduced deviceto-device measurement variability from 10% to 2%. Repeated-measure analysis using the generalized estimating equation (GEE) method showed a significant monotonic decrease in relative RBC flow rate with storage from Week 0. By the end of storage, relative RBC flow rate decreased by 22 AE 6% on average. CONCLUSIONS:The suspension of microbeads was successfully used as a flow reference to increase reproducibility of RBC deformability measurements using the MVA. Deformability results suggest an early and late aging phase for stored RCCs, with significant decreases between successive weeks suggesting a highly sensitive measurement method.R ed blood cells (RBCs) are responsible for O 2 and CO 2 transport through blood vessels. 1 The deformability of healthy discoidal RBCs allows their passage through much narrower blood capillaries. 2,3 Over their 120-day lifespan, aging RBCs are prone to various alterations that are countered by beneficial enzymatic activity and shedding of damaged cell components via microvesiculation. RBCs with impaired deformability are trapped in the spleen and liver, and senescent markers are recognized by macrophages, leading to RBCs engulfment and degradation. The senescent RBCs are removed daily resulting in a heterogeneous age distribution of the RBCs in the bloodstream.In blood banking operations, RBCs are separated from other blood components before being dispersed in an additive solution and stored at temperature (T) = 2-6°C, allowing preservation of RBC concentrates (RCCs) for up to 42 days prior to transfusion. 4 During storage, RBCs undergo many changes, which include intracellular [K + ] and [Na + ] imbalance, ATP and 2,3-DPG depletion, cytoskeleton and membrane component alteration, decrease of cellular antioxidant capability, and exposure of markers of senescence. 5 These changes (collectively labeled "storage lesions") result in generation of microvesicles, impairment of deformability and hemolysis, 5-7 and a...

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In vitroandex vivomeasurement of the biophysical properties of blood using microfluidic platforms and animal models

Cited by 42 publications

References 135 publications

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

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

Integrated automated particle tracking microfluidic enables high‐throughput cell deformability cytometry for red cell disorders

Development of a flow standard to enable highly reproducible measurements of deformability of stored red blood cells in a microfluidic device

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