A model for micro-front dynamics using a ϕ4 equation.

In this article, we propose a numerical model based on the ϕ4 equation to simulate the dynamics of a front inside a microchannel that features an imperfection at a sidewall to different flow rates. The micro-front displays pinning-depinning phenomena without damped oscillations in the aftermath. To model this behavior, we propose a ϕ4 model with a localized external force and a damping coefficient. Numerical simulations with a constant damping coefficient show that the front displays pinning-depinning phenomena showing damped oscillations once the imperfection is overcome. Replacing the constant damping coefficient with a parabolic spatial function, we reproduce accurately the experimental front-defect interaction.

Normalization of Blood Viscosity According to the Hematocrit and the Shear Rate.

The rheological properties of blood depend highly on the properties of its red blood cells: concentration, membrane elasticity, and aggregation. These properties affect the viscosity of blood as well as its shear thinning behavior. Using an experimental analysis of the interface advancement of blood in a microchannel, we determine the viscosity of different samples of blood. In this work, we present two methods that successfully normalize the viscosity of blood for a single and for different donors, first according to the concentration of erythrocytes and second according to the shear rate. The proposed methodology is able to predict the health conditions of the blood samples by introducing a non-dimensional coefficient that accounts for the response to shear rate of the different donors blood samples. By means of these normalization methods, we were able to determine the differences between the red blood cells of the samples and define a range where healthy blood samples can be described by a single behavior.

Microfluidics Approach to the Mechanical Properties of Red Blood Cell Membrane and Their Effect on Blood Rheology.

In this article, we describe the general features of red blood cell membranes and their effect on blood flow and blood rheology. We first present a basic description of membranes and move forward to red blood cell membranes' characteristics and modeling. We later review the specific properties of red blood cells, presenting recent numerical and experimental microfluidics studies that elucidate the effect of the elastic properties of the red blood cell membrane on blood flow and hemorheology. Finally, we describe specific hemorheological pathologies directly related to the mechanical properties of red blood cells and their effect on microcirculation, reviewing microfluidic applications for the diagnosis and treatment of these diseases.

Blood Rheological Characterization of ß-Thalassemia Trait and Iron Deficiency Anemia Using Front Microrheometry.

The purpose of this work is to develop a hematocrit-independent method for the detection of beta-thalassemia trait (ß-TT) and iron deficiency anemia (IDA), through the rheological characterization of whole blood samples from different donors. The results obtained herein are the basis for the development of a front microrheometry point-of-care device for the diagnosis and clinical follow-up of ß-TT patients suffering hematological diseases and alterations in the morphology of the red blood cell (RBC). The viscosity is calculated as a function of the mean front velocity by detecting the sample fluid-air interface advancing through a microfluidic channel. Different viscosity curves are obtained for healthy donors, ß-TT and IDA samples. A mathematical model is introduced to compare samples of distinct hematocrit, classifying the viscosity curve patterns with respect to the health condition of blood. The viscosity of the fluid at certain shear rate values varies depending on several RBC factors such as shape and size, hemoglobin (Hb) content, membrane rigidity and hematocrit concentration. Blood and plasma from healthy donors are used as reference. To validate their potential clinical value as a diagnostic tool, the viscosity results are compared to those obtained by the gold-standard method for RBC deformability evaluation, the Laser-Optical Rotational Red Cell Analyzer (LoRRCA).

Pitting of malaria parasites in microfluidic devices mimicking spleen interendothelial slits.

The spleen is a hematopoietic organ that participates in cellular and humoral immunity. It also serves as a quality control mechanism for removing senescent and/or poorly deformable red blood cells (RBCs) from circulation. Pitting is a specialized process by which the spleen extracts particles, including malaria parasites, from within circulating RBCs during their passage through the interendothelial slits (IES) in the splenic cords. To study this physiological function in vitro, we have developed two microfluidic devices modeling the IES, according to the hypothesis that at a certain range of mechanical stress on the RBC, regulated through both slit size and blood flow, would force it undergo the pitting process without affecting the cell integrity. To prove its functionality in replicating pitting of malaria parasites, we have performed a characterization of P. falciparum-infected RBCs (P.f.-RBCs) after their passage through the devices, determining hemolysis and the proportion of once-infected RBCs (O-iRBCs), defined by the presence of a parasite antigen and absence of DAPI staining of parasite DNA using a flow cytometry-based approach. The passage of P.f.-RBCs through the devices at the physiological flow rate did not affect cell integrity and resulted in an increase of the frequency of O-iRBCs. Both microfluidic device models were capable to replicate the pitting of P.f.-RBCs ex vivo by means of mechanical constraints without cellular involvement, shedding new insights on the role of the spleen in the pathophysiology of malaria.

Microrheometer for Biofluidic Analysis: Electronic Detection of the Fluid-Front Advancement.

The motivation for this study was to develop a microdevice for the precise rheological characterization of biofluids, especially blood. The method presented was based on the principles of rheometry and fluid mechanics at the microscale. Traditional rheometers require a considerable amount of space, are expensive, and require a large volume of sample. A mathematical model was developed that, combined with a proper experimental model, allowed us to characterize the viscosity of Newtonian and non-Newtonian fluids at different shear rates. The technology presented here is the basis of a point-of-care device capable of describing the nonlinear rheology of biofluids by the fluid/air interface front velocity characterization through a microchannel. The proposed microrheometer uses a small amount of sample to deliver fast and accurate results, without needing a large laboratory space. Blood samples from healthy donors at distinct hematocrit percentages were the non-Newtonian fluid selected for the study. Water and plasma were employed as testing Newtonian fluids for validation of the system. The viscosity results obtained for the Newtonian and non-Newtonian fluids were consistent with pertinent studies cited in this paper. In addition, the results achieved using the proposed method allowed distinguishing between blood samples with different characteristics.

The role of asymmetric interactions on the effect of habitat destruction in mutualistic networks.

Plant-pollinator mutualistic networks are asymmetric in their interactions: specialist plants are pollinated by generalist animals, while generalist plants are pollinated by a broad range involving specialists and generalists. It has been suggested that this asymmetric--or disassortative--assemblage could play an important role in determining the observed equal susceptibility of specialist and generalist plants under habitat destruction. At the core of the analysis of the phenomenon lies the observation that specialist plants, otherwise candidates to extinction, could cope with the disruption thanks to their interaction with a few generalist pollinators. We present a theoretical framework that supports this thesis. We analyze a dynamical model of a system of mutualistic plants and pollinators, subject to the destruction of their habitat. We analyze and compare two families of interaction topologies, ranging from highly assortative to highly disassortative ones, as well as real pollination networks. We found that several features observed in natural systems are predicted by the mathematical model. First, there is a tendency to increase the asymmetry of the network as a result of the extinctions. Second, an entropy measure of the differential susceptibility to extinction of specialist and generalist species show that they tend to balance when the network is disassortative. Finally, the disappearance of links in the network, as a result of extinctions, shows that specialist plants preserve more connections than the corresponding plants in an assortative system, enabling them to resist the disruption.