Biosensing of Haemorheological Properties Using Microblood Flow Manipulation and Quantification.

The biomechanical properties of blood have been used to detect haematological diseases and disorders. The simultaneous measurement of multiple haemorheological properties has been considered an important aspect for separating the individual contributions of red blood cells (RBCs) and plasma. In this study, three haemorheological properties (viscosity, time constant, and RBC aggregation) were obtained by analysing blood flow, which was set to a square-wave profile (steady and transient flow). Based on a simplified differential equation derived using a discrete circuit model, the time constant for viscoelasticity was obtained by solving the governing equation rather than using the curve-fitting technique. The time constant (λ) varies linearly with respect to the interface in the coflowing channel (ß). Two parameters (i.e., average value: <λ>, linear slope: dλdß) were newly suggested to effectively represent linearly varying time constant. <λ> exhibited more consistent results than dλdß. To detect variations in the haematocrit in blood, we observed that the blood viscosity (i.e., steady flow) is better than the time constant (i.e., transient flow). The blood viscosity and time constant exhibited significant differences for the hardened RBCs. The present method was then successfully employed to detect continuously varying haematocrit resulting from RBC sedimentation in a driving syringe. The present method can consistently detect variations in blood in terms of the three haemorheological properties.

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

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.

Simultaneous measurement of blood pressure and RBC aggregation by monitoring on-off blood flows supplied from a disposable air-compressed pump.

Haematological diseases significantly increase RBC aggregation. Specifically, RBC aggregation is considerably varied by haematological factors including cellular properties, and suspending medium properties. Thus, in order to ensure consistent measurement of RBC aggregation, it is necessary to measure RBC aggregation and blood pressure simultaneously. Here, a method for simultaneously measuring RBC aggregation and blood pressure is demonstrated by analyzing blood flows supplied from a disposable air-compressed pump. A microfluidic device is composed of two parallel microfluidic channels (i.e., PBS channel and blood channel), an inlet, and outlets. After the PBS channel is filled with the PBS solution, the outlets of the PBS channel are completely closed with two pinch valves. Under varying blood flow rates of the disposable pump, the blood pressure index (PI) is quantified by analyzing the image intensity of RBCs in the PBS channel. Thereafter, at stasis, the RBC aggregation index (AI) is calculated by analyzing the image intensity of blood in the blood channel. First, under a constant blood flow-rate of a syringe pump, the image intensity of RBCs collected in the PBS channel (IPC) is linearly proportional to blood pressure estimated in the blood channel (PBC). Second, with respect to variations in the blood flow-rate of the proposed pump, the IPC and PBC decrease gradually over time. Two blood pressure indices (PI [PBC], and PI [IPC]) are obtained by averaging temporal variations in the PBC and IPC, respectively. The results of the regression analysis indicate that the coefficient of the linear regression yields a higher value of R2 = 0.9051. Subsequently, the PI (IPC) is effectively used to estimate blood pressure. Finally, the variations in blood pressure and RBC aggregation are obtained by using aggregation-enhanced blood samples and deformability-reduced blood samples. Thus, the proposed method leads to consistent variations in the PI and AI, when compared with the previous results. The experimental demonstrations indicate that two indices (PI and AI) are effectively used to simultaneously quantify blood pressure and RBC aggregation.

Change in Perfusion Angiography During Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma Predicts Short-Term Outcomes.

OBJECTIVE. The purpose of this study is to quantitatively assess perfusion reductions occurring in hepatocellular carcinoma (HCC) during transcatheter arterial chemoembolization (TACE) using 2D perfusion angiography and to evaluate the relationships between various 2D perfusion angiography parameter changes and short-term tumor response. SUBJECTS AND METHODS. This prospective study included 172 patients (144 men and 28 women; mean [± SD] age, 65.4 ± 10.2 years) who underwent TACE for HCC between November 2015 and November 2017. Two-dimensional perfusion angiography was performed before and after TACE. Pre- and postprocedural CT images were also reviewed. Index lesions were defined as all discrete lesions 1.5 cm or larger. The tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors. Periprocedural 2D perfusion angiography parameters, including the arrival time, time to peak, wash-in rate, width, AUC, and mean transit time, were compared using the Wilcoxon signed rank test. Correlations between 2D perfusion angiography parameter changes and objective tumor response were evaluated using multivariate logistic regression analysis. RESULTS. A total of 187 lesions meeting the inclusion criteria were identified in 172 patients. All analyzed 2D perfusion angiography parameters were significantly different after versus before TACE (p < 0.001). A significant relationship between periprocedural change in AUC and short-term tumor response was found (odds ratio, 1.535; 95% CI, 1.314-1.793; p < 0.001). CONCLUSION. Two-dimensional perfusion angiography could objectively quantify perfusion reductions and predict short-term tumor response to TACE in patients with HCC.

In vitro and ex vivo measurement of the biophysical properties of blood using microfluidic platforms and animal models.

Haemorheologically impaired microcirculation, such as blood clotting or abnormal blood flow, causes interrupted blood flows in vascular networks. The biophysical properties of blood, including blood viscosity, blood viscoelasticity, haematocrit, red blood bell (RBC) aggregation, erythrocyte sedimentation rate and RBC deformability, have been used to monitor haematological diseases. In this review, we summarise several techniques for measuring haemorheological properties, such as blood viscosity, RBC deformability and RBC aggregation, using in vitro microfluidic platforms. Several methodologies for the measurement of haemorheological properties with the assistance of an extracorporeal rat bypass loop are also presented. We briefly discuss several emerging technologies for continuous, long-term, multiple measurements of haemorheological properties under in vitro or ex vivo conditions.

The effectiveness of using magnetic resonance imaging in syncope patients visiting an emergency department: A case-control study.

OBJECTIVE: To evaluate the effectiveness of brain magnetic resonance imaging in excluding neurological causes in patients with syncope. METHODS: This retrospective, observational, cohort study was conducted at the Chonnam National University Hospital, Gwangju, South Korea, and comprised medical record of patients with syncope from January 2011 to February 2016. The ratio of abnormal findings, the characteristics of the patients who showed abnormal findings and the relationships between the presence of neurological problem and other clinical factors were analysed. SPSS 18 was used for statistical analysis. RESULTS: Of the 1,045 patients, 142(13.5%) underwent additional magnetic resonance imaging. The results showed that 15(10.6%) patients had abnormal findings indicating neurological problems; of them, 9(60%) showed vascular stenosis, 4(27%) showed cerebral infarction, and 2(13%) showed brain tumours. The neurological problems shown were significantly higher for older patients (p=0.006) and those with the underlying diseases of hypertension (p=0.014) and coronary artery disease (p=0.008). Of these patients in particular, age (p=0.036) and history of coronary artery disease (p=0.029) were significantly associated with abnormal findings in their magnetic resonance imaging. CONCLUSIONS: Although there are no specific neurological examinations or computed tomography findings currently used in patients with syncope in the emergency department, magnetic resonance imaging may be performed to exclude neurological causes in older patients as well as those with a history of coronary artery disease.

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

Correction for 'Continuous and simultaneous measurement of the biophysical properties of blood in a microfluidic environment' by Yang Jun Kang, Analyst, 2016, 141, 6583-6597.

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

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.

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

The malaria parasite Plasmodium falciparum (Pf) changes the structure and mechanical properties of red blood cells (RBCs). These changes decrease deformability and increase cytoadherence of Pf-infected RBCs to the vascular endothelium, eventually leading to flow occlusions in capillary vessels. In this study, to detect Pf-infected RBCs effectively, deformability and viscosity of blood sample are measured simultaneously and indirectly by quantifying blood flow in a microfluidic device. The microfluidic device is designed by mimicking a Wheatstone-bridge electric circuit. To measure RBC deformability, a deformability assessment chamber (DAC) at the left lower side channel has parallel microfluidic filters. After delivering blood sample and 1× PBS solution at the same flow rate, hemodynamic properties are measured using a time-resolved microparticle image velocimetry technique. Blood volume delivered into the DAC for 200 s is evaluated as a deformability index. Subsequently, blood viscosity is quantified by monitoring blood-filled width of parallel flows in the microfluidic device. The proposed method is applied to evaluate variations in biophysical properties of blood samples partially mixed with normal RBCs and hardened RBCs. As a result, RBC deformability is more effective than blood viscosity in the detection of blood samples with hardened RBC volume fraction of 5%. The microfluidic device is also applied to detect Pf-infected RBCs. When parasitemia is greater than 0.515% for ring stage, 0.0544% for trophozoite stage, and 0.0054% for schizont stage, the measured velocity fields show unstable behavior because of cytoadherence of Pf-infected RBCs. Blood volume delivered into the DAC significantly decreases with increasing parasitemia. The experimental method proposed in this study can detect Pf-infected RBCs with good accuracy.

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

The biophysical properties of blood have been considered as promising indices for effectively screening the cardiovascular diseases. In this study, a method for the continuous and simultaneous measurement of the biophysical properties of blood, including viscosity, viscoelasticity, and RBC (red blood cell) aggregation is suggested, using a microfluidic device. The microfluidic device has two inlets (A, B), two outlets (A, B), two identical side channels, and one bridge channel. To sequentially induce steady and transient flows of blood samples, a blood sample is carefully delivered into the inlet (A) at a pulsatile flow rate (Q) (Qmax = 1 mL h-1, Qmin = 0 mL h-1, T = 240 s). By operating a pinch valve connected to the outlet (A), the blood flow is stopped or passed in the left-lower side channel. Three biophysical properties of the blood sample are quantified by analyzing the flow rate in the left-upper side channel (QµPIV), the image intensity in the left-lower side channel (〈I〉Blood), and the blood-filled width in the right-lower side channel (αBlood). First, based on the modified parallel flow method, the blood viscosity (µBlood) is measured by analyzing the variation in αBlood. Second, using a discrete fluidic circuit model, the time constant (λ) is evaluated by analyzing temporal variations in QµPIV and 1/(1 - αBlood). Then, the blood elasticity (GBlood) is calculated by assuming the linear Maxwell model (i.e., λ = µBlood/GBlood). Third, the RBC aggregation is quantified in terms of three parameters (〈I〉Slope, ARatio, and AUpp) obtained by analyzing temporal variations in the image intensity. From the experimental demonstrations using various blood samples, it is concluded that the proposed method has the ability to measure the biophysical properties of blood with consistency, as compared with the previous methods. In the near future, the proposed method will be employed for evaluating variations in the biophysical properties of blood, circulating in the extracorporeal rat bypass loop.

Deformability measurement of red blood cells using a microfluidic channel array and an air cavity in a driving syringe with high throughput and precise detection of subpopulations.

Red blood cell (RBC) deformability has been considered a potential biomarker for monitoring pathological disorders. High throughput and detection of subpopulations in RBCs are essential in the measurement of RBC deformability. In this paper, we propose a new method to measure RBC deformability by evaluating temporal variations in the average velocity of blood flow and image intensity of successively clogged RBCs in the microfluidic channel array for specific time durations. In addition, to effectively detect differences in subpopulations of RBCs, an air compliance effect is employed by adding an air cavity into a disposable syringe. The syringe was equally filled with a blood sample (V(blood) = 0.3 mL, hematocrit = 50%) and air (V(air) = 0.3 mL). Owing to the air compliance effect, blood flow in the microfluidic device behaved transiently depending on the fluidic resistance in the microfluidic device. Based on the transient behaviors of blood flows, the deformability of RBCs is quantified by evaluating three representative parameters, namely, minimum value of the average velocity of blood flow, clogging index, and delivered blood volume. The proposed method was applied to measure the deformability of blood samples consisting of homogeneous RBCs fixed with four different concentrations of glutaraldehyde solution (0%-0.23%). The proposed method was also employed to evaluate the deformability of blood samples partially mixed with normal RBCs and hardened RBCs. Thereafter, the deformability of RBCs infected by human malaria parasite Plasmodium falciparum was measured. As a result, the three parameters significantly varied, depending on the degree of deformability. In addition, the deformability measurement of blood samples was successfully completed in a short time (∼10 min). Therefore, the proposed method has significant potential in deformability measurement of blood samples containing hematological diseases with high throughput and precise detection of subpopulations in RBCs.

Role of interventional radiology in trauma care: retrospective study from single trauma center experience.

PURPOSE: Although interventional management is now regarded as essential in trauma care, the effect on clinical result remains uncertain. We conducted this retrospective study to figure out the role of interventional management in trauma care. MATERIALS AND METHODS: Medical records of patients enrolled in the trauma database of our trauma center were reviewed for the period of January 2009 to December 2012. During this period, we have evaluated how many interventional procedures were conducted and the clinical effect of interventional procedure on trauma care. RESULTS: Based on our institutional trauma database, medical records of 2017 patients were reviewed (male/female, 1475:542; mean age, 50.03 years). Their mean injury severity score was approximately 26.28. Among them, 111 patients have been treated with interventional procedure. The number of interventional procedures increased significantly over time, up to 15% (P < .005). During the same period, the overall survival rate did not show significant change. The survival rate of the patients, who have been treated with interventional procedures for traumatic vascular injury, was higher than possibility of survival from trauma injury severity score (86.4% vs 65.59%). CONCLUSION: The need for interventional procedure in trauma care is increasing. Although interventional procedure could not affect the overall survival rate in trauma care, it can improve survival rate remarkably in patients with traumatic vascular injury.

Microfluidic biosensor for monitoring temporal variations of hemorheological and hemodynamic properties using an extracorporeal rat bypass loop.

In this study, we propose a novel microfluidic biosensor for monitoring hemorheological and hemodynamic properties using an extracorporeal rat bypass loop. To monitor temporal variations of biophysical properties including viscosity, flow rate, and pressure of rat blood, a complex fluidic network is established by connecting the abdominal aorta and jugular vein to an extracorporeal bypass loop including a flow stabilizer and a microfluidic biosensor. Three biophysical properties are simultaneously measured through label-free operation and sensorless detection based on two sequential flow controls in the microfluidic channel. A discrete fluidic-circuit model is employed to derive analytical formulas for the complex fluidic network. First, to evaluate the measurement accuracy of the proposed method, a peristaltic pump is used as substitute for a rat. The flow rate and viscosity of 20% glycerin (test fluid) circulating within the fluidic network are measured, and then the results are compared with those obtained using conventional methods. The normal differences between two measurement methods are less than 4%. Then, the proposed method is used to monitor temporal variations in biophysical properties of blood circulating within the complex fluidic network under normal and continuous hemodilution conditions. Rats require at least 30 min to adapt to different fluidic environments. The flow rate, pressure, and hematocrit of rat blood tend to decrease gradually because of continuous hemodilution effect. Furthermore, the reduced flow rate increases blood viscosity under hemodilution condition. These experiments demonstrate that the proposed method can effectively monitor temporal variations of biophysical properties of rat blood under ex vivo conditions.

Biomechanical Assessment of Red Blood Cells in Pulsatile Blood Flows.

As rheological properties are substantially influenced by red blood cells (RBCs) and plasma, the separation of their individual contributions in blood is essential. The estimation of multiple rheological factors is a critical issue for effective early detection of diseases. In this study, three rheological properties (i.e., viscoelasticity, RBC aggregation, and blood junction pressure) are measured by analyzing the blood velocity and image intensity in a microfluidic device. Using a single syringe pump, the blood flow rate sets to a pulsatile flow pattern (Qb[t] = 1 + 0.5 sin(2πt/240) mL/h). Based on the discrete fluidic circuit model, the analytical formula of the time constant (λb) as viscoelasticity is derived and obtained at specific time intervals by analyzing the pulsatile blood velocity. To obtain RBC aggregation by reducing blood velocity substantially, an air compliance unit (ACU) is used to connect polyethylene tubing (i.d. = 250 µm, length = 150 mm) to the blood channel in parallel. The RBC aggregation index (AI) is obtained by analyzing the microscopic image intensity. The blood junction pressure (ß) is obtained by integrating the blood velocity within the ACU. As a demonstration, the present method is then applied to detect either RBC-aggregated blood with different concentrations of dextran solution or hardened blood with thermally shocked RBCs. Thus, it can be concluded that the present method has the ability to consistently detect differences in diluent or RBCs in terms of three rheological properties.

Biomechanical Investigation of Red Cell Sedimentation Using Blood Shear Stress and Blood Flow Image in a Capillary Chip.

Blood image intensity has been used to detect erythrocyte sedimentation rate (ESR). However, it does not give information on the biophysical properties of blood samples under continuous ESR. In this study, to quantify mechanical variations of blood under continuous ESR, blood shear stress and blood image intensity were obtained by analyzing blood flows in the capillary channel. A blood sample is loaded into a driving syringe to demonstrate the proposed method. The blood flow rate is set in a periodic on-off pattern. A blood sample is then supplied into a capillary chip, and microscopic blood images are captured at specific intervals. Blood shear stress is quantified from the interface of the bloodstream in the coflowing channel. τ0 is defined as the maximum shear stress obtained at the first period. Simultaneously, ESRτ is then obtained by analyzing temporal variations of blood shear stress for every on period. AII is evaluated by analyzing the temporal variation of blood image intensity for every off period. According to the experimental results, a shorter period of T = 4 min and no air cavity contributes to the high sensitivity of the two indices (ESRτ and AII). The τ0 exhibits substantial differences with respect to hematocrits (i.e., 30-50%) as well as diluents. The ESRτ and AII showed a reciprocal relationship with each other. Three suggested properties represented substantial differences for suspended blood samples (i.e., hardened red blood cells, different concentrations of dextran solution, and fibrinogen). In conclusion, the present method can detect variations in blood samples under continuous ESR effectively.

Quantification of Blood Viscoelasticity under Microcapillary Blood Flow.

Blood elasticity is quantified using a single compliance model by analyzing pulsatile blood flow. However, one compliance coefficient is influenced substantially by the microfluidic system (i.e., soft microfluidic channels and flexible tubing). The novelty of the present method comes from the assessment of two distinct compliance coefficients, one for the sample and one for the microfluidic system. With two compliance coefficients, the viscoelasticity measurement can be disentangled from the influence of the measurement device. In this study, a coflowing microfluidic channel was used to estimate blood viscoelasticity. Two compliance coefficients were suggested to denote the effects of the polydimethylsiloxane (PDMS) channel and flexible tubing (C1), as well as those of the RBC (red blood cell) elasticity (C2), in a microfluidic system. On the basis of the fluidic circuit modeling technique, a governing equation for the interface in the coflowing was derived, and its analytical solution was obtained by solving the second-order differential equation. Using the analytic solution, two compliance coefficients were obtained via a nonlinear curve fitting technique. According to the experimental results, C2/C1 is estimated to be approximately 10.9-20.4 with respect to channel depth (h = 4, 10, and 20 µm). The PDMS channel depth contributed simultaneously to the increase in the two compliance coefficients, whereas the outlet tubing caused a decrease in C1. The two compliance coefficients and blood viscosity varied substantially with respect to homogeneous hardened RBCs or heterogeneous hardened RBCs. In conclusion, the proposed method can be used to effectively detect changes in blood or microfluidic systems. In future studies, the present method can contribute to the detection of subpopulations of RBCs in the patient's blood.

Contributions of Red Blood Cell Sedimentation in a Driving Syringe to Blood Flow in Capillary Channels.

The erythrocyte sedimentation rate (ESR), which has been commonly used to detect physiological and pathological diseases in clinical settings, has been quantified using an interface in a vertical tube. However, previous methods do not provide biophysical information on blood during the ESR test. Therefore, it is necessary to quantify the individual contributions in terms of viscosity and pressure. In this study, to quantify RBC sedimentation, the image intensity (Ib) and interface (ß) were obtained by analyzing the blood flow in the microfluidic channels. Based on threshold image intensity, the corresponding interfaces of RBCs (Ib > 0.15) and diluent (Ib < 0.15) were employed to obtain the viscosities (µb, µ0) and junction pressures (Pb, P0). Two coefficients (CH1, CH2) obtained from the empirical formulas (µb = µ0 [1 + CH1], Pb = P0 [1 + CH2]) were calculated to quantify RBC sedimentation. The present method was then adopted to detect differences in RBC sedimentation for various suspended blood samples (healthy RBCs suspended in dextran solutions or plasma). Based on the experimental results, four parameters (µ0, P0, CH1, and CH2) are considered to be effective for quantifying the contributions of the hematocrit and diluent. Two coefficients exhibited more consistent trends than the conventional ESR method. In conclusion, the proposed method can effectively detect RBC sedimentation.

Red Blood Cell Sedimentation Index Using Shear Stress of Blood Flow in Microfluidic Channel.

Red blood cell sedimentation has been used as a promising indicator of hematological diseases and disorders. However, to address several issues (i.e., syringe installation direction, blood on-off flow control, image-based quantification, and hemodilution) raised by the previous methods, it is necessary to devise a new method for the effective quantification of red blood cell sedimentation under a constant blood flow. In this study, the shear stress of a blood flow is estimated by analyzing an interface in a co-flowing channel to quantify the red blood cell sedimentation in blood syringes filled with blood (hematocrit = 50%). A red blood cell sedimentation index is newly suggested by analyzing the temporal variations in the shear stress. According to the experimental investigation, the sedimentation index tends to decrease at a higher flow rate. A higher level of hematocrit has a negative influence on the sedimentation index. As a performance demonstration of the present method, the red blood cell sedimentation processes of various test bloods were quantitatively compared in terms of the shear stress, image intensity, and sedimentation velocity. It was found that the proposed index provided a more than 10-fold increase in sensitivity over the previous method (i.e., image intensity). Additionally, it provided more consistent results than another conventional sedimentation method (sedimentation velocity). In conclusion, the present index can be effectively adopted to monitor the red blood cell sedimentation in a 10-min blood delivery.

Sequential quantification of blood and diluent using red cell sedimentation-based separation and pressure-induced work in a microfluidic channel.

The erythrocyte sedimentation method has been widely used to detect inflammatory diseases. However, this conventional method still has several drawbacks, such as a large blood volume (∼1 mL) and difficulty in continuous monitoring. Most importantly, image-based methods cannot quantify RBC-rich blood (blood) and RBC-free blood (diluent) simultaneously. In this study, instead of visualizing interface movement in the blood syringe, a simple method is proposed to quantify blood and diluent in microfluidic channels sequentially. The hematocrit was set to 25% to enhance RBC sedimentation and form two layers (blood and diluent) in the blood syringe. An air cavity (∼300 µL) inside the blood syringe was secured to completely remove dead volumes (∼200 µL) in fluidic paths (syringe needle and tubing). Thus, a small blood volume (Vb = 50 µL) suctioned into the blood syringe is sufficient for supplying blood and diluent in the blood channel sequentially. The relative ratio of blood resident time (RBC-to-diluent separation) was quantified using λb, which was obtained by quantifying the image intensity of blood flow. After the junction pressure (Pj) and blood volume (V) were obtained by analyzing the interface in the coflowing channel, the averaged work (Wp [Pa mm3]) was calculated and adopted to detect blood and diluent, respectively. The proposed method was then applied with various concentrations of dextran solution to detect aggregation-elevated blood. The Wp of blood and diluent exhibited substantial differences with respect to dextran solutions ranging from Cdex = 10 to Cdex = 40 mg mL-1. Moreover, λb did not exhibit substantial differences in blood with Cdex > 10 mg mL-1. The variations in λb were comparable to those of the previous method based on interface movement in the blood syringe. In conclusion, the WP could detect blood as well as diluents more effectively than λb. Furthermore, the proposed method substantially reduced the blood volume from 1 mL to 50 µL.

Assessment of Blood Biophysical Properties Using Pressure Sensing with Micropump and Microfluidic Comparator.

To identify the biophysical properties of blood samples consistently, macroscopic pumps have been used to maintain constant flow rates in a microfluidic comparator. In this study, the bulk-sized and expensive pump is replaced with a cheap and portable micropump. A specific reference fluid (i.e., glycerin solution [40%]) with a small volume of red blood cell (RBC) (i.e., 1% volume fraction) as fluid tracers is supplied into the microfluidic comparator. An averaged velocity () obtained with micro-particle image velocimetry is converted into the flow rate of reference fluid (Qr) (i.e., Qr = CQ × Ac × , Ac: cross-sectional area, CQ = 1.156). Two control variables of the micropump (i.e., frequency: 400 Hz and volt: 150 au) are selected to guarantee a consistent flow rate (i.e., COV < 1%). Simultaneously, the blood sample is supplied into the microfluidic channel under specific flow patterns (i.e., constant, sinusoidal, and periodic on-off fashion). By monitoring the interface in the comparator as well as Qr, three biophysical properties (i.e., viscosity, junction pressure, and pressure-induced work) are obtained using analytical expressions derived with a discrete fluidic circuit model. According to the quantitative comparison results between the present method (i.e., micropump) and the previous method (i.e., syringe pump), the micropump provides consistent results when compared with the syringe pump. Thereafter, representative biophysical properties, including the RBC aggregation, are consistently obtained for specific blood samples prepared with dextran solutions ranging from 0 to 40 mg/mL. In conclusion, the present method could be considered as an effective method for quantifying the physical properties of blood samples, where the reference fluid is supplied with a cheap and portable micropump.