Microfluidic electrical impedance assessment of red blood cell-mediated microvascular occlusion

Man, Yuncheng; Maji, Debnath; An, Ran; Ahuja, Sanjay P.; Little, Jane A.; Suster, Michael A.; Mohseni, Pedram; Gürkan, Umut A.

doi:10.1039/d0lc01133a

Cited by 32 publications

(24 citation statements)

References 95 publications

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“…After the RBCs were deformed under the influence of this shear stress, the dynamic RBC recovery was monitored and analyzed according to the Kelvin-Voigt model, allowing the measurement of an elastic shear modulus of RBCs submitted to different shear rates. Even more recently, another group [7][8][9] developed a microfluidic impedance red cell assay (MIRCA) in order to measure RBC transition through narrow openings and also challenged to some extent the concept of 'fluid drop-like' RBCs whose deformation was assumed to be mostly related to viscosity with little or no elastic component. The authors defined new parameters such as an RBC occlusion index (ROI) and an RBC electrical impedance index (REI), which measure the cumulative percentage of vessel occlusion and the impedance change, respectively.…”

Section: Introductionmentioning

confidence: 99%

Metabolic Influences Modulating Erythrocyte Deformability and Eryptosis

et al. 2021

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Many factors in the surrounding environment have been reported to influence erythrocyte deformability. It is likely that some influences represent reversible changes in erythrocyte rigidity that may be involved in physiological regulation, while others represent the early stages of eryptosis, i.e., the red cell self-programmed death. For example, erythrocyte rigidification during exercise is probably a reversible physiological mechanism, while the alterations of red blood cells (RBCs) observed in pathological conditions (inflammation, type 2 diabetes, and sickle-cell disease) are more likely to lead to eryptosis. The splenic clearance of rigid erythrocytes is the major regulator of RBC deformability. The physicochemical characteristics of the surrounding environment (thermal injury, pH, osmolality, oxidative stress, and plasma protein profile) also play a major role. However, there are many other factors that influence RBC deformability and eryptosis. In this comprehensive review, we discuss the various elements and circulating molecules that might influence RBCs and modify their deformability: purinergic signaling, gasotransmitters such as nitric oxide (NO), divalent cations (magnesium, zinc, and Fe++), lactate, ketone bodies, blood lipids, and several circulating hormones. Meal composition (caloric and carbohydrate intake) also modifies RBC deformability. Therefore, RBC deformability appears to be under the influence of many factors. This suggests that several homeostatic regulatory loops adapt the red cell rigidity to the physiological conditions in order to cope with the need for oxygen or fuel delivery to tissues. Furthermore, many conditions appear to irreversibly damage red cells, resulting in their destruction and removal from the blood. These two categories of modifications to erythrocyte deformability should thus be differentiated.

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Section: Introductionmentioning

confidence: 99%

Metabolic Influences Modulating Erythrocyte Deformability and Eryptosis

et al. 2021

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“…The rise of microfluidics in the last two decades has enabled the increase in experimental options to study RBCs' properties and their effect on blood flow [89,[100][101][102]. The easiness of replicating small structures in microfluidics allowed the development of various designs and structures to observe and analyze the deformation of RBCs [103][104][105]. Typical microfluidics approaches consider a forced, or gradual, constriction of RBCs, as they circulate through very narrow slits.…”

Section: Hemodynamics and Hemorheology For A Single Cellmentioning

confidence: 99%

“…In severe cases, ISCs obstruct microvessels, altering the normal circulation of blood. In the last decade, microfluidic devices have played the important role of determining the biophysical characteristics of sickle red cells [175], measuring the mechanical stresses on erythrocytes in sickle cell disease [176], studying vaso-oclusion [104,177,178], identifying biophysical markers [179,180], segregating sickle cells [181], and developing point-of-care diagnostic technologies for low-resource settings [182] and possible treatments [183].…”

Section: Hemorheological Pathologies and Emergent Microfluidics Diagn...mentioning

confidence: 99%

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

et al. 2022

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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.

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“…In turn, the measurement of pressure at specific locations in a microfluidic device allows us to determine the permeability of the pattern [22] as well as correlate pressure changes with visual observations at the microscale in order to explain processes that govern subsurface systems (e.g., hydrocarbon reservoirs) [23]. Local measurements of thermal conductivity and electrical impedance can also be useful, e.g., to detect cellular response during culture [24], assess blood samples [25], count particles [26], determine the sample position in a microfluidic channel [27], or differentiate fluids in multi-phase fluid flow experiments [28].…”

Section: Introductionmentioning

confidence: 99%

“…When sensors are integrated within a microfluidic device, they increase the functionality and value of the device. Unfortunately, the fabrication of bespoke microfluidic devices with integrated sensors can be difficult, time consuming, and expensive because this requires advanced know-how and specialized equipment e.g., to develop a sensor, perform its accurate deposition and patterning, and seal the microfluidic chip without damaging the sensor [23][24][25][26][27][28][29][30]. Such microfluidic devices may also impose some limitations in conducting experiments.…”

Section: Introductionmentioning

confidence: 99%

Manufacturing of Microfluidic Devices with Interchangeable Commercial Fiber Optic Sensors

Wlodarczyk

MacPherson

Hand

et al. 2021

Sensors

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In situ measurements are highly desirable in many microfluidic applications because they enable real-time, local monitoring of physical and chemical parameters, providing valuable insight into microscopic events and processes that occur in microfluidic devices. Unfortunately, the manufacturing of microfluidic devices with integrated sensors can be time-consuming, expensive, and “know-how” demanding. In this article, we describe an easy-to-implement method developed to integrate various “off-the-shelf” fiber optic sensors within microfluidic devices. To demonstrate this, we used commercial pH and pressure sensors (“pH SensorPlugs” and “FOP-MIV”, respectively), which were “reversibly” attached to a glass microfluidic device using custom 3D-printed connectors. The microfluidic device, which serves here as a demonstrator, incorporates a uniform porous structure and was manufactured using a picosecond pulsed laser. The sensors were attached to the inlet and outlet channels of the microfluidic pattern to perform simple experiments, the aim of which was to evaluate the performance of both the connectors and the sensors in a practical microfluidic environment. The bespoke connectors ensured robust and watertight connection, allowing the sensors to be safely disconnected if necessary, without damaging the microfluidic device. The pH SensorPlugs were tested with a pH 7.01 buffer solution. They measured the correct pH values with an accuracy of ±0.05 pH once sufficient contact between the injected fluid and the measuring element (optode) was established. In turn, the FOP-MIV sensors were used to measure local pressure in the inlet and outlet channels during injection and the steady flow of deionized water at different rates. These sensors were calibrated up to 140 mbar and provided pressure measurements with an uncertainty that was less than ±1.5 mbar. Readouts at a rate of 4 Hz allowed us to observe dynamic pressure changes in the device during the displacement of air by water. In the case of steady flow of water, the pressure difference between the two measuring points increased linearly with increasing flow rate, complying with Darcy’s law for incompressible fluids. These data can be used to determine the permeability of the porous structure within the device.

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Microfluidic electrical impedance assessment of red blood cell-mediated microvascular occlusion

Abstract: Alterations in the deformability of red blood cells (RBCs), occurring in hemolytic blood disorders such as sickle cell disease (SCD), contributes to vaso-occlusion and disease pathophysiology. However, there are few...

Cited by 32 publications

References 95 publications

Metabolic Influences Modulating Erythrocyte Deformability and Eryptosis

Metabolic Influences Modulating Erythrocyte Deformability and Eryptosis

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

Manufacturing of Microfluidic Devices with Interchangeable Commercial Fiber Optic Sensors

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