Electrical Detection of the Mechanical Alteration of Sickling Red Blood Cells within a Microfluidic Capillary Network (original) (raw)
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2021 43rd Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC)
Combining microfluidic with sensors enables the development of smart analysis systems. Microelectrodes can be embedded within the microchannels network for electrical sensing, electrochemical analysis or impedance measurement. However, at the laboratory scale, the assembly between microfluidic network and electrical parts on the substrate remains an issue. This paper first discusses the principles of biosensing, and then proposes an original device integrating microfluidics with microelectrodes for the analysis of red blood cells transit in a structure mimicking micro-vascular flow. Some results concerning red blood cells discrimination of sickle cell disease are discussed with statistical analysis.
HAL (Le Centre pour la Communication Scientifique Directe), 2022
Thanks to their membrane elasticity and fluidity, red blood cells (RBCs) are capable to pass through the smallest microcapillaries while exchanging oxygen and CO2 with organs. For several blood disorders like sickle cells disease (SCD), RBCs lose their deformability leading to vaso-occlusions. To assess the deformability of RBC, successive mechanical stresses are applied in our device mimicking blood microcapillaries network, while RBCs circulating being monitored optically by microscopy. Normal and sickled RBCs behaviors are compared using such approach. This device could be a promising tool for the diagnostic of different blood disorders.
Scientific Reports, 2020
This paper describes the use of a microfluidic device comprising channels with dimensions mimicking those of the smallest capillaries found in the human microcirculation. The device structure, associated with a pair of microelectrodes, provides a tool to electrically measure the transit time of red blood cells through fine capillaries and thus generate an electrical signature for red blood cells in the context of human erythroid genetic disorders, such as sickle cell disease or hereditary spherocytosis, in which red cell elasticity is altered. Red blood cells from healthy individuals, heated or not, and red blood cells from patients with sickle cell disease or hereditary spherocytosis where characterized at a single cell level using our device. Transit time and blockade amplitude recordings were correlated with microscopic observations, and analyzed. The link between the electrical signature and the mechanical properties of the red blood cells is discussed in the paper, with greater...
Sickle cell disorder (SCD) is a multisystem disease with heterogeneous phenotypes. Although all patients have the mutated haemoglobin (Hb) in the SS phenotype, the severity and frequency of complications are variable. When exposed to low oxygen tension, the Hb molecule becomes dense and, forms tactoids which, lead to the peculiar sickled shapes of the affected red blood cells, giving the disorder its name. This sickle cell morphology is responsible for the profound and widespread pathologies associated with this disorder, such as vaso-occlusive crisis, (VOC). How much of the clinical manifestation is due to sickled erythrocytes and what is due to the relative contributions of other elements in the blood, especially in the microcapillary circulation, is usually not visualized and quantified for each patient during clinical management. Here, we used a microfluidic microcirculation mimetic (MMM) which has 187 capillary-like constrictions to impose deformations on erythrocytes of SCD pa...
2021 21st International Conference on Solid-State Sensors, Actuators and Microsystems (Transducers)
Bioimpedance measurements using microfluidic systems play an increasingly important role in cell analysis. In this paper, a microfluidic device mimicking the vasculature, in particular blood microcapillaries, and equipped with electrodes for bioimpedance sensing is described. Red blood cells, from patients suffering from sickle cell disease, were analyzed and discriminated in this device according to the physical parameters. The statistical position of different subpopulations on the Gaussian distribution of the whole sickle cell population was analyzed. A discrimination between sickle cell subpopulations, related to different density states, was achieved.
Frontiers in Molecular Biosciences, 2021
Sickle cell disease (SCD) is the monogenic hemoglobinopathy where mutated sickle hemoglobin molecules polymerize to form long fibers under deoxygenated state and deform red blood cells (RBCs) into predominantly sickle form. Sickled RBCs stick to the vascular bed and obstruct blood flow in extreme conditions, leading to acute painful vaso-occlusion crises (VOCs) – the leading cause of mortality in SCD. Being a blood disorder of deformed RBCs, SCD manifests a wide-range of organ-specific clinical complications of life (in addition to chronic pain) such as stroke, acute chest syndrome (ACS) and pulmonary hypertension in the lung, nephropathy, auto-splenectomy, and splenomegaly, hand-foot syndrome, leg ulcer, stress erythropoiesis, osteonecrosis and osteoporosis. The physiological inception for VOC was initially thought to be only a fluid flow problem in microvascular space originated from increased viscosity due to aggregates of sickled RBCs; however, over the last three decades, multi...
High-throughput microfluidic characterization of erythrocyte shape and mechanical variability
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The motion of red blood cells (RBCs) in microchannels is important for microvascular blood flow and biomedical applications such as blood analysis in microfluidics. The current understanding of the complexity of RBC shapes and dynamics in microchannels is mainly based on several simulation studies, but there are a few systematic experimental investigations. Here, we present a combined study, which systematically characterizes RBC behavior for a wide range of flow rates and channel sizes. Even though simulations and experiments generally show good agreement, experimental observations demonstrate that there is no single well-defined RBC state for fixed flow conditions, but rather a broad distribution of states. This result can be attributed to the inherent variability in RBC mechanical properties, which is confirmed by a model that takes the variation in RBC shear elasticity into account. This represents a significant step toward a quantitative connection between RBC behavior in micro...
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Procedia Engineering, 2016
Microfluidic devices exploit combined physical, chemical and biological phenomena that could be unique in the sub-millimeter dimensions. The blood is a non-Newtonian fluid, containing particulate and soluble elements, which penetrates the whole body carrying a wealth of biomedical information. The design of microfluidic devices capable of extracting immediately this information is the current goal of development Point-of-Care (POC) medical devices. We examined the characteristics of blood flow in specially designed microfluidic devices having different geometric structure and material composition with the aim of defining suitable conditions for sensitive detection of changes in the interactions between particulate elements of the blood and the adequately modified surfaces of the microfluidic system. As a model experiment we demonstrated the fast analysis of the AB0 blood group system, applying respective antibody reagents and capillary blood samples with different blood groups. We showed that by tuning the hydrophilicity of the surface and capillary dimensions of the microfluidic system it is possible to detect precisely the red blood cell binding to the capillary walls by monitoring the flow rate characteristics in an autonomous microfluidic system. Our proof-of-concept results point to a novel direction in blood analysis in autonomous microfluidic systems and also provide the basis for the construction of a simple quantitative device for blood group determination.