Microhemodynamics Laboratory

Research

Plasma Separation Based On Cell-Free Layer Formation Phenomenon

Plasma

Separation of plasma from whole blood is an important and critical step in medical diagnostics. The current conventional method for the separation is mainly relied on use of centrifugation which is time consuming and requires an established laboratory setting. Recently, thanks to the advancement in microfludics, the separaon without the requirement of centrifugation has been possible. However, there are still several difficulties in achieving maximum efficiency for collecting plasma such as optimization of flow rates, clogging of channels by blood clotting, and low purity of collected plasma. In particular, the low purity of collected plasma requires additional separation step usually with use of a centrifuge. Therefore, the present study proposes a new method of plasma separation by the use of formation of a cell-free layer that occurs in micro-channels and micro-vessels flow.

 The aim of this study is to utilize the phenomenon of the cell-free layer formation in the microcirculation as a tool for the plasma separation. This pure hemodynamic based phenomenon would allow better separation of plasma with an advantage of flexibility for ease integration to biosensors without any integration or addition of mechanical/electraical forces to the device. Successful completion of this study would provide not only a method to efficiently separate plasma from whole blood but also the possibility of integrating this device with biosensors for direct detection of biomarkers from plasma. The proposed method would pave way for increasing the accuracy and efficiency of the plasma separation.

In Vivo and In Vitro Study into Understanding Pathophysiology in Microcirculation

in vitro
In Vitro Experiment on Cell Free Layer

Many clinical studies have reported that abnormal alteration of blood properties can be a radical cause of physiological malfunctions in hemorheological disorders including heart diseases, diabetes mellitus, and malaria. In these pathological conditions, intensified red blood cell (RBC) aggregability, rigidified RBC and anomalous hematocrit levels are commonly found. However, despite the clinical significance of these findings, information on how such rheological changes of blood influence hemodynamics and gas transport in the microcirculation is currently very limited. Thus, this study aims to provide such information through in vivo experiments and computational simulations.

 
In Vivo
In Vivo Experiment in Microcirculation

Since cell-free layer (CFL) formation in microvessels has been of great interest as an important hemodynamic parameter in understanding the microcirculatory response to physiological changes, our proposed approaches will focus on revealing physiological and pathophysiological roles of the CFL in the microcirculation. To ascertain its roles, detailed quantitative information on the CFL characteristics in the presence of hemorheological abnormalities will be acquired by pursuing the following specific aims. Firstly, in vivo CFL data will be obtained from small arterioles in the rat cremaster muscle at pathophysiological levels of RBC aggregability, deformability and hematocrit. In addition, with the use of microsensors developed by our lab, oxygen and nitric oxide levels in the tissue will be measured under the physiological and pathophysiological conditions. Finally, numerical models for hemodynamics and gas tranport in the arterioles will be developed to better understand the pathophysiological role of CFL in microcirlculatory functions. The scientific findings obtained in this research will pave the way for a more detailed exploration of blood disorders, possibly leading to development of better diagnostic tools.

 

Numerical Studies into the Rheological Properties of Red Blood Cells

Computational Methods : Lattice Boltzmann Method (LBM) and Immersed Boundary Method (IBM)

LBM
D2Q9 LBM model
IBM
IBM Model

 

LBM is a recent technique that has been shown to be as accurate as traditional CFD methods. Furthermore LBM is able to integrate arbitrarily complex geometries at a reduced computational cost. LBM simplifies Boltzmann’s original formulation by discretizing both time and space. In this discretization, fluid particle positions are confined to the node of a lattice. Instead of considering the entire continua of velocity directions and magnitudes, and varying particle mass, variations of fluid particle momenta are discretized into several finite directions. In addition to a fluid solver such as LBM, IBM has been widely used in the simulation of blood flow. In this method, the effect of a moving boundary is accounted for by a force density that is distributed to the Cartesian mesh in the vicinity of the moving boundary. The force density is calculated from the boundary’s constitutive law. IBM is suitable for modeling fluid-structure interaction in blood flow simulations where plasma and RBC mechanics are solved in a partitioned approach.

 

Numerical simulation of two red blood cells (RBCs) with different aggregation strength

 

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According to previous studies, most aggregates in blood flow consist of RBCs doublet-pairs therefore the understanding of doublet dynamics has scientific importance in describing hemodynamics. Hence, the numerical simulation of a doublet was conducted in a simple shear flow condition. To study the aggregation behavior of the doublet, we employed the aggregation model described by the Morse type potential function, which is based on depletion theory.

Numerical simulation of multi-cells with different deformability

 

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Physiological Condition

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Artificial Condition

 

RBCs in our blood vessels have different deformability due to a population mixture of both young and old RBCs hence the hemodynamics will be affected by this varying deformability across the population. In this study, three kinds of RBC were utilized in the simulation in order to represent this physiological condition. The blue RBCs represent the control, which have the mean level of deformability. The green RBCs represent more deformable cells and the red RBCs represent less deformable cells.
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