Whole blood viscosity and red blood cell adhesion: Potential biomarkers for targeted and curative therapies in sickle cell disease.

Sickle cell disease (SCD) is a recessive genetic blood disorder exhibiting abnormal blood rheology. Polymerization of sickle hemoglobin, due to a point mutation in the ß-globin gene of hemoglobin, results in aberrantly adhesive and stiff red blood cells (RBCs). Hemolysis, abnormal RBC adhesion, and abnormal blood rheology together impair endothelial health in people with SCD, which leads to cumulative systemic complications. Here, we describe a microfluidic assay combined with a micro particle image velocimetry technique for the integrated in vitro assessment of whole blood viscosity (WBV) and RBC adhesion. We examined WBV and RBC adhesion to laminin (LN) in microscale flow in whole blood samples from 53 individuals with no hemoglobinopathies (HbAA, N = 10), hemoglobin SC disease (HbSC, N = 14), or homozygous SCD (HbSS, N = 29) with mean WBV of 4.50 cP, 4.08 cP, and 3.73 cP, respectively. We found that WBV correlated with RBC count and hematocrit in subjects with HbSC or HbSS. There was a significant inverse association between WBV and RBC adhesion under both normoxic and physiologically hypoxic (SpO2 of 83%) tests, in which lower WBV associated with higher RBC adhesion to LN in subjects with HbSS. Low WBV has been found by others to associate with endothelial activation. Altered WBV and abnormal RBC adhesion may synergistically contribute to the endothelial damage and cumulative pathophysiology of SCD. These findings suggest that WBV and RBC adhesion may serve as clinically relevant biomarkers and endpoints in assessing emerging targeted and curative therapies in SCD.

Influence of near-wall PIV data on recirculation hemodynamics in a patient-specific moderate stenosis: Experimental-numerical comparison.

BACKGROUND: Recirculation zones within the blood vessels are known to influence the initiation and progression of atherosclerotic lesions. Quantification of recirculation parameters with accuracy remains subjective due to uncertainties in measurement of velocity and derived wall shear stress (WSS). OBJECTIVE: The primary aim is to determine recirculation height and length from PIV experiments while validating with two different numerical methods: finite-element (FE) and -volume (FV). Secondary aim is to analyze how FE and FV compare within themselves. METHODS: PIV measurements were performed to obtain velocity profiles at eight cross sections downstream of stenosis at flow rate of 200 ml/min. WSS was obtained by linear/quadratic interpolation of experimental velocity measurements close to wall. RESULTS: Recirculation length obtained from PIV technique was 1.47 cm and was within 2.2% of previously reported in-vitro measurements. Derived recirculation length from PIV agreed within 6.8% and 8.2% of the FE and FV calculations, respectively. For lower shear rate, linear interpolation with five data points results in least error. For higher shear rate either higher order (quadratic) interpolation with five data points or lower order (linear) with lesser (three) data points leads to better results. CONCLUSION: Accuracy of the recirculation parameters is dependent on number of near wall PIV data points and the type of interpolation algorithm used.

Experimental investigation and computational modeling of hydrodynamics in bifurcating microchannels.

Methods involving microfluidics have been used in several chemical, biological and medical applications. In particular, a network of bifurcating microchannels can be used to distribute flow in a large space. In this work, we carried out experiments to determine hydrodynamic characteristics of bifurcating microfluidic networks. We measured pressure drop across bifurcating networks of various complexities for various flow rates. We also measured planar velocity fields in these networks by using particle image velocimetry. We further analyzed hydrodynamics in these networks using mathematical and computational modeling. Our results show that the experimental frictional resistances of complex bifurcating microchannels are 25-30% greater than that predicted by Navier-Stokes equations. Experimentally measured velocity profiles indicate that flow distributes equally at a bifurcation regardless of the complexity of the network. Flow division other than bifurcation such as trifurcation or quadruplication can lead to heterogeneities. These findings were verified by the results from the numerical simulations.