Red Blood Cell Suspensions Research Articles

Predictive values of clinical data,molecular biomarkers, and echocardiographic measurements in preterm infants with bronchopulmonary dysplasia.

We aimed to use molecular biomarkers and clinical data and echocardiograms that were collected during admission to predict bronchopulmonary dysplasia (BPD) in preterm infants with gestational age ≤32 weeks. Eighty-two patients (40 with BPD, BPD group and 42 healthy as controls, non-BPD group) admitted to the Department of Neonatology of the Children's Hospital of Soochow University between October 1, 2018, and February 29, 2020, were enrolled in this study at the tertiary hospital. Basic clinical data on the perinatal period, echocardiographic measurements, and molecular biomarkers (N-terminal-pro-B-brain natriuretic peptide, NT-proBNP) were collected. We used multiple logistic regression analysis to establish an early predictive model for detecting BPD development in preterm infants of gestational age ≤32 weeks. We also used a receiver operating characteristic curve to assess the sensitivity and specificity of the model. No significant differences were found between the BPD and non-BPD groups in terms of sex, birth weight, gestational age, incidence of asphyxia, maternal age, gravidity, parity, mode of delivery, premature rupture of membranes >18 h, use of prenatal hormones, placental abruption, gestational diabetes mellitus, amniotic fluid contamination, prenatal infections, and maternal diseases. The use of caffeine, albumin, gamma globulin; ventilation; days of FiO2 ≥ 40%; oxygen inhalation time; red blood cell suspension infusion volume (ml/kg); and proportion of infants who received total enteral nutrition (120 kcal/kg.d) ≥24 d after birth were higher in the BPD group than in the non-BPD group. The levels of hemoglobin, hematocrit, and albumin in the BPD group were significantly lower than those in the non-BPD group. The total calorie intake was significantly lower in the BPD group on the 3rd, 7th, and 14th day after birth than in the non-BPD group (P < 0.05). The incidence rates of patent ductus arteriosus (PDA), pulmonary hypertension, and tricuspid regurgitation were significantly higher in the BPD group than in the non-BPD group (P < 0.05). The serum level of NT-proBNP 24 h after birth was significantly higher in the BPD group than in the non-BPD group (P < 0.05). Serum NT-proBNP levels were significantly higher in infants with severe BPD than in those with mild or moderate BPD (P < 0.05). As there were various risk factors for BPD, a combining clinical data, molecular biomarkers, and echocardiogram measurements can be valuable in predicting the BPD. The tricuspid regurgitation flow rate (m/s), NT-proBNP (pg/ml), ventilator-associated pneumonia, days of FiO2 ≥ 40% (d), red blood cell suspension infusion volume (ml/kg), and proportion of infants who received total enteral nutrition (120 kcal/kg.d) ≥24 d after birth were the most practical factors considered for designing an appropriate model for predicting the risk of BPD.

Application of Modified DTT Methods to Reduce the Interference of Daratumumab on Serological Detection

To modified the classic dithiothreitol (DTT) method for treating red blood cells (RBCs) in Technical Manual of American Association of Blood Banks（AABB） and evaluate its application value in pre-transfusion examination of patients treated with daratumumab. The classic 0.2 mol/L DTT method was improved in terms of PBS, DTT concentration, donor RBCs concentration (suspended/packed) and sample processing time. The modified DTT methods and AABB classic DTT method were applied to the blood matching tests of 12 multiple myeloma patients treated with daratumumab. The effect of treating panel RBCs with modified DTT methods on the detection of other irregular antibodies was evaluated by using antiserum and antibody reagents with known antibody properties. Two modified DTT methods were established (method 1: changed the concentration of DTT to 0.01 mol/L; method 2: changed the concentration of DTT to 0.02 mol/L and replaced the packed RBCs with 3% RBCs suspension). The optimal treatment time was 35 min for the modified DTT methods. At this time, the pan-agglutination caused by daratumumab was eliminated, but the detection of antibodies such as anti-E, anti-JKa, anti-M were not affected, and the titer of anti-K antibodies was only slightly decreased. The modified DTT methods were effective, which can eliminate the interference of daratumumab while retaining the activity of the Kell blood group system, and can replace the current classic DTT method in AABB Technical Manual.

Interplay between size and softness in the vascular dynamics of microcarriers

The geometry and mechanical properties of blood-borne particles play a major role in determining their vascular behavior and ability to evade immune cell sequestration. Within this context, the transport dynamics of deformable microcarriers (MCs) in a red blood cell (RBC) suspension is systematically investigated. Trajectories and the margination propensity of nominally spherical particles with five different diameters (DMC = 0.5, 1, 2, 3, and 4 μm) and three levels of deformability (stiff, soft, and extra soft) are studied for two different vessel calibers (capillary: 10 μm; arteriole: 50 μm) under three different hematocrits (Hct = 10%, 20%, and 30%). The multi-component suspension is modeled as elastic membranes and elastic solids representing RBC and MC, respectively, immersed in Newtonian fluid simulated by smoothed particle hydrodynamics method. The results document the existence of two regimes: (i) a “collision force” regime where fast-moving RBCs push sufficiently small particles toward the wall; (ii) a “lift force” regime where sufficiently large particles migrate away from the wall. Between these two regimes, a maximum in margination propensity appears, which depends on the particle size, deformability, and flow conditions. For the considered vessel calibers and hematocrits, 2 μm MC offers the highest margination propensity. The vascular dynamics of small MC (DMC ≤ 0.5 μm) is hardly influenced by their deformability, whereas extra soft MCs behave similarly to RBCs. In addition to the limitations related to the two-dimensional analysis, these simulations suggest that moderately deformable micrometric carriers would more efficiently marginate and seek for vascular targets in the microcirculation.

Observation on the clinical outcomes of continued pregnancy following cesarean scar pregnancy in 55 women

Objective: To observe the clinical outcomes of continued pregnancy in pregnant women with cesarean scar pregnancy (CSP). Methods: A retrospective analysis was performed on the pregnancy outcomes of 55 pregnant women who were diagnosed with CSP at the Second Affiliated Hospital of Army Medical University during the first trimester of pregnancy from August 1st, 2018 to October 31st, 2021 and strongly requested to continue the pregnancy. Results: Of the 55 pregnant women, 15 terminated the pregnancy in the first trimester, 1 underwent hysterotomy at 23 weeks of gestation due to cervical dilation, and 39 (71%, 39/55) continued pregnancy to the third trimester achieving live births via cesarean section. The gestational age of the 39 pregnant women delivered by cesarean section was 35+6 weeks (range: 28+5-39+2 weeks), of whom 7 cases at 28+5-33+6 weeks, 20 cases at 34-36+6 weeks, and 12 cases at 37-39+2 weeks. The results of pathological examination were normal placenta in 3 cases (8%, 3/39), placenta creta in 4 cases (10%, 4/39), placenta increta in 9 cases (23%, 9/39) and placenta percreta in 23 cases (59%, 23/39). Among the 36 pregnant women who were pathologically confirmed as placenta accreta spectrum disorders (PAS) after surgery, the last prenatal ultrasonography showed placenta previa in 27 cases (75%, 27/36) and not observed placenta previa in 9 cases. The median intraoperative blood loss, autologous blood transfusion, and allogeneic suspended red blood cell infusion of 39 pregnant women during cesarean section were 1 000 ml (300-3 500 ml), 300 ml (0-2 000 ml) and 400 ml (0-2 400 ml), respectively. The uterine preservation rate was 100% (39/39), and only 1 case received cystostomy due to intracystic hemorrhage. The birth weight of the newborn was 2 580 g (1 350-3 800 g), and 1 case of mild asphyxia. Conclusions: Pregnant women with CSP who continue pregnancy under close monitoring after adequate ultrasound evaluation and doctor-patient communication could achieve better maternal and infant outcomes, but pregnant women with CSP are highly likely to continue pregnancy and develop into PAS. Effective hemostasis means and multidisciplinary team cooperation are needed in perinatal period for ensuring maternal and fetal safety.

Anisotropic short-range attractions precisely model branched erythrocyte aggregates.

Homogeneous suspensions of red blood cells (RBCs or erythrocytes) in blood plasma are unstable in the absence of driving forces and form elongated stacks, called rouleaux. These erythrocyte aggregates are often branched porous networks - a feature that existing red blood cell aggregation models and simulations fail to predict exactly. Here we establish that alignment-dependent attractive forces in a system of dimers can precisely generate branched structures similar to RBC aggregates observed under a microscope. Our simulations consistently predict that the growth rate of typical mean rouleau size remains sub-linear - a hallmark from past studies - which we also confirm by deriving a reaction kernel taking into account appropriate collision cross-section, approach velocities, and an area-dependent sticking probability. The system exhibits unique features such as the existence of percolated and/or single giant cluster states, multiple coexisting mass-size scalings, and transition to a branched phase upon fine-tuning of model parameters. Upon decreasing the depletion thickness we find that the percolation threshold increases but the morphology of the structures opens up towards an increased degree of branching. Remarkably the system self-organizes to produce a universal power-law size distribution scaling irrespective of the model parameters.

Autosplenectomy may be a good prognostic sign in sickle cell diseases

Background: Sickle cell diseases (SCDs) are inborn and destructive processes on vascular endothelium, particularly at the capillaries. Methods: Patients with red blood cells (RBCs) transfusions of less than 50 units in their lives were put into the first and 50 units or higher were put into the second groups. Results: There were 224 patients in the first and 92 patients in the second groups. Mean ages were similar in them (28.9 vs 30.0 years, respectively, p&gt;0.05). The male ratio was higher in the second group (45.5% vs 64.1%, p&lt;0.001). In contrast to the lower prevalence of autosplenectomy (56.2% vs 45.6%, p&lt;0.05), painful crises per year, digital clubbing, chronic obstructive pulmonary disease (COPD), leg ulcers, stroke, chronic renal disease (CRD), and coronary heart disease (CHD) were all higher in the second group (p&lt;0.05 for all). Conclusion: The sickled or just hardened RBCs-induced capillary endothelial damage initiates at birth, and terminates with multiorgan failures even at childhood. Although RBCs suspensions and corticosteroids in acute, and aspirin with an anti-inflammatory dose plus low-dose warfarin plus hydroxyurea both in acute and chronic phases decrease severity, survivals are still shortened in both genders, dramatically. In contrast to the lower prevalence of autosplenectomy, painful crises per year, digital clubbing, COPD, leg ulcers, stroke, CRD, and CHD were higher in the second group. So there may be an inverse relationship between prevalence of autosplenectomy and severity of SCDs, and spleen may act as a chronic inflammatory focus as a filter of blood for these abnormally hardened RBCs. Key words: Sickle cell diseases, sickled or just hardened red blood cells, capillary endothelial edema, myocardial infarction, stroke, sudden deaths, autosplenectomy

As a good prognostic sign, Autosplenectomy is higher in females in Sickle Cell Diseases

Background: Sickle cell diseases (SCDs) are inborn and destructive processes on vascular endothelium, particularly at the capillaries. Methods: All patients with the SCDs were included. Results: We studied 222 males and 212 females with similar ages (30.8 vs 30.3 years, p&gt;0.05, respectively). Although the higher prevalence of autosplenectomy (50.4% vs 53.3%, p&lt;0.05), transfused units of red blood cells (RBCs) in their lives (48.1 vs 28.5, p=0.000), disseminated teeth losses (5.4% vs 1.4%, p&lt;0.001), ileus (7.2% vs 1.4%, p&lt;0.001), cirrhosis (8.1% vs 1.8%, p&lt;0.001), leg ulcers (19.8% vs 7.0%, p&lt;0.001), clubbing (14.8% vs 6.6%, p&lt;0.001), coronary heart disease (CHD) (18.0% vs 13.2%, p&lt;0.05), chronic renal disease (CRD) (9.9% vs 6.1%, p&lt;0.05), chronic obstructive pulmonary disease (COPD) (25.2% vs 7.0%, p&lt;0.001), and stroke (12.1% vs 7.5%, p&lt;0.05) were all lower in females. Conclusion: The sickled or just hardened RBCs-induced capillary endothelial damage initiates at birth, and terminates with multiorgan failures even at childhood. Although RBCs suspensions and corticosteroids in acute, and aspirin with an anti-inflammatory dose plus low-dose warfarin plus hydroxyurea both in acute and chronic phases decrease severity, survivals are still shortened in both genders, dramatically. Although the higher prevalence of autosplenectomy, transfused units of RBCs in their lives disseminated teeth losses, ileus, cirrhosis, leg ulcers, clubbing, CHD, CRD, COPD, and stroke were all lower in females. So there may be an inverse relationship between autosplenectomy and severity of SCDs, and spleen may act as a chronic inflammatory focus as a filter of blood for these sickled or just hardened RBCs. Key words: Sickled or just hardened red blood cells, capillary endothelial edema, myocardial infarction, stroke, sudden deaths, autosplenectomy, female gender

Male Gender alone may be a bad Prognostic Factor in Sickle Cell Diseases

Background: Sickle cell diseases are inborn and destructive processes on vascular endothelium, particularly at the capillaries. Methods: All patients were included. Results: We studied 222 males and 212 females with similar ages (30.8 vs 30.3 years, p&gt;0.05, respectively). Smoking (23.8% vs 6.1%, p&lt;0.001), alcohol (4.9% vs 0.4%, p&lt;0.001), transfused red blood cells (RBCs) in their lives (48.1 vs 28.5 units, p=0.000), disseminated teeth losses (5.4% vs 1.4%, p&lt;0.001), chronic obstructive pulmonary disease (COPD) (25.2% vs 7.0%, p&lt;0.001), ileus (7.2% vs 1.4%, p&lt;0.001), cirrhosis (8.1% vs 1.8%, p&lt;0.001), leg ulcers (19.8% vs 7.0%, p&lt;0.001), clubbing (14.8% vs 6.6%, p&lt;0.001), coronary heart disease (CHD) (18.0% vs 13.2%, p&lt;0.05), chronic renal disease (CRD) (9.9% vs 6.1%, p&lt;0.05), and stroke (12.1% vs 7.5%, p&lt;0.05) were all higher, and autosplenectomy (50.4% vs 53.3%, p&lt;0.05) and mean age of mortality were lower in males (30.2 vs 33.3 years, p&lt;0.05). Conclusion: The sickled or just hardened RBCs-induced capillary endothelial damage initiates at birth, and terminates with multiorgan failures even at childhood. Although RBCs suspensions and corticosteroids in acute, and aspirin with an anti-inflammatory dose plus low-dose warfarin plus hydroxyurea both in acute and chronic phases decrease severity, survivals are still shortened in both genders, dramatically. Transfused units of RBCs in their lives, disseminated teeth losses, COPD, ileus, cirrhosis, leg ulcers, clubbing, CHD, CRD, and stroke were all higher, and autosplenectomy and mean age of mortality were lower in males which can not be explained by effects of smoking and alcohol alone at these younger mean ages, relatively. Key words: Sickle cell diseases, sickled or just hardened red blood cells, capillary endothelial edema, myocardial infarction, stroke, sudden deaths, male gender

Segmental flexibility of spectrin reflects erythrocyte membrane deformability

The frequency-dependent contribution of spectrin, the main cytoskeletal protein of red blood cell (RBC) membrane, to the complex admittance and capacitance of suspended RBCs have revealed two dielectric relaxations, βsp (1.4 MHz) and γ1sp (7 MHz). The strength of these relaxations was related to the ability of RBC membrane to deform. In this study the two relaxations were inhibited by N-ethylmaleimide (up to 5 mM), known to impair the RBC deformability, and the degree of inhibition, i.e., the number of accessible SH-groups on spectrin, depended on the deformation of RBC membrane. Dithiothreitol (up to 5 mM), which does not affect RBC deformability, did not affect the above dielectric relaxations in line with the absence of S-S groups on spectrin. Phenylhydrazine (up to 3 mM) and hydrogen hydroperoxide (up to 450 μM) are known to denature the haemoglobin of RBCs producing nanoparticles (globins) that bind to spectrin turning the RBC membrane rigid. At the same concentrations they were shown to inhibit progressively the two relaxations on spectrin. The results are in line with the involvement of some globin-sized segments of spectrin in the dielectric activity of spectrin and in the ability of RBC plasma membrane to deform.

Cross-talk between red blood cells and plasma influences blood flow and omics phenotypes in severe COVID-19.

Coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and can affect multiple organs, among which is the circulatory system. Inflammation and mortality risk markers were previously detected in COVID-19 plasma and red blood cells (RBCs) metabolic and proteomic profiles. Additionally, biophysical properties, such as deformability, were found to be changed during the infection. Based on such data, we aim to better characterize RBC functions in COVID-19. We evaluate the flow properties of RBCs in severe COVID-19 patients admitted to the intensive care unit by using microfluidic techniques and automated methods, including artificial neural networks, for an unbiased RBC analysis. We find strong flow and RBC shape impairment in COVID-19 samples and demonstrate that such changes are reversible upon suspension of COVID-19 RBCs in healthy plasma. Vice versa, healthy RBCs resemble COVID-19 RBCs when suspended in COVID-19 plasma. Proteomics and metabolomics analyses allow us to detect the effect of plasma exchanges on both plasma and RBCs and demonstrate a new role of RBCs in maintaining plasma equilibria at the expense of their flow properties. Our findings provide a framework for further investigations of clinical relevance for therapies against COVID-19 and possibly other infectious diseases.

Erythrocyte Respiratory Activity of the Mitochondrial Complex of the Black Sea Thornback Ray (Raja clavata L.) under the Influence of Certain Activators and Inhibitors In Vitro

Global warming implies the risk of a changing oxygen regime in the seas and oceans of our planet. The mitochondrial complex of nuclear erythrocytes of cartilaginous fish, as the energy basis of blood cells, has repeatedly encountered such climatic fluctuations throughout their evolutionary history. In this regard, the features of the adaptive strategy of the erythrocyte mitochondrial complex in the thornback ray (Raja clavata L.) are of interest from the evolutionary and ecological points of view. The rate of oxygen consumption in resuspended (Ht = 25–30%) erythrocytes taken from the Black Sea thornback ray in saline was studied by the polarographic method. A high “basal” rate of respiration in the erythrocytes of the thornback ray was shown, which ranged from 10.5 to 21.6 pmol O2 min−1·106 cells. The addition of substrates of the mitochondrial respiration activators glutamate, maleate, and succinate to the erythrocyte suspension caused a 2–6-fold increase in the respiratory activity of thornback ray erythrocytes. In cases where the rate of respiration of erythrocytes was high, protonophore–dinitrophenol caused an inhibition of the activity of mitochondrial respiration. At low respiration rates of erythrocytes, its effect was opposite and caused a stimulation of mitochondrial respiration. Oligomycin caused a significant inhibition of the respiratory activity of the red blood cell suspension of the thornback ray. This suppression of cell respiration was enhanced under conditions of exposure to the permeabilization of erythrocytes with digitonin. This can be recommended as one of the ways to block the respiratory activity of erythrocytes in cartilaginous fish. Another way of effectively blocking the respiration of the mitochondrial complex of the thornback ray’s erythrocytes was the effect of the blockers rotenone and sodium azide. The peculiarity of the mitochondria of the erythrocytes of the thornback ray was the absence of the complete inhibition of respiration by sodium azide (NaN3), which is characteristic of the mitochondria of other fish species. Our data on the activation of the “respiration” of erythrocytes in fish indicate that the potential capabilities of cold-blooded and warm-blooded vertebrates have rather similar characteristics. This may indicate the initial “laying” of the architecture of the inner membrane to support the energy potential of the mitochondria of the cell.

Examining the universality of the hemolysis power law model from simulations of the FDA nozzle using calibrated model coefficients.

Computational fluid dynamics (CFD) is widely used to predict mechanical hemolysis in medical devices. The most popular hemolysis model is the stress-based power law model that is based on an empirical correlation between hemoglobin release from red blood cells (RBCs) and the magnitude of flow-induced stress and exposure time. Empirical coefficients are traditionally calibrated using data from experiments in simplified Couette-type blood-shearing devices with uniform-shear laminar flow and well-defined exposure times. Use of such idealized coefficients in simulations of real medical devices with complex hemodynamics is thought to be a primary reason for the historical inaccuracy of absolute hemolysis predictions using the power law model. Craven et al.(Biomech Model Mechanobiol 18:1005-1030, 2019) recently developed a CFD-based Kriging surrogate modeling approach for calibrating empirical coefficients in real devices that could potentially be used to more accurately predict absolute hemolysis. In this study, we use the FDA benchmark nozzle to investigate whether utilizing such calibrated coefficients improves the predictive accuracy of the standard Eulerian power law model. We first demonstrate the credibility of our CFD flow simulations by comparing with particle image velocimetry measurements. We then perform hemolysis simulations and compare the results with in vitro experiments. Importantly, the simulations use coefficients calibrated for the flow of a suspension of bovine RBCs through a small capillary tube, which is relatively comparable to the flow of bovine blood through the FDA nozzle. The results show that the CFD predictions of relative hemolysis in the FDA nozzle are reasonably accurate. The absolute predictions are, however, highly inaccurate with modified index of hemolysis values from CFD in error by roughly three orders of magnitude compared with the experiments, despite using calibrated model coefficients from a relatively similar geometry. We rigorously examine the reasons for the inaccuracy that include differences in the flow conditions in the hemolytic regions of each device and the lack of universality of the hemolysis power law model that is entirely empirical. Thus, while the capability to predict relative hemolysis is valuable for product development, further improvements are needed before the power law model can be relied upon to accurately predict the absolute hemolytic potential of a medical device.

Hemoglobin is an oxygen-dependent glutathione buffer adapting the intracellular reduced glutathione levels to oxygen availability

Fast changes in environmental oxygen availability translate into shifts in mitochondrial free radical production. An increase in intraerythrocytic reduced glutathione (GSH) during deoxygenation would support the detoxification of exogenous oxidants released into the circulation from hypoxic peripheral tissues. Although reported, the mechanism behind this acute oxygen-dependent regulation of GSH in red blood cells remains unknown.This study explores the role of hemoglobin (Hb) in the oxygen-dependent modulation of GSH levels in red blood cells. We have demonstrated that a decrease in Hb O2 saturation to 50% or less observed in healthy humans while at high altitude, or in red blood cell suspensions results in rising of the intraerythrocytic GSH level that is proportional to the reduction in Hb O2 saturation. This effect was not caused by the stimulation of GSH de novo synthesis or its release during deglutathionylation of Hb's cysteines. Using isothermal titration calorimetry and in silico modeling, we observed the non-covalent binding of four molecules of GSH to oxy-Hb and the release of two of them upon deoxygenation. Localization of the GSH binding sites within the Hb molecule was identified. Oxygen-dependent binding of GSH to oxy-Hb and its release upon deoxygenation occurred reciprocally to the binding and release of 2,3-bisphosphoglycerate. Furthermore, noncovalent binding of GSH to Hb moderately increased Hb oxygen affinity. Taken together, our findings have identified an adaptive mechanism by which red blood cells may provide an advanced antioxidant defense to respond to oxidative challenges immediately upon deoxygenation.

Red blood cell magnetophoresis as a function of oxygen partial pressure

Red blood cell (RBC) magnetophoresis is a function of the concentration of dissolved oxygen (O2) in normal RBCs measured by cell tracking velocimetry (CTV). The hemoglobin (Hb) magnetic susceptibility changes from diamagnetic (when fully oxygenated, oxyHb) to paramagnetic (when fully deoxygenated, deoxyHb) resulting in a small shift in the normal RBC diamagnetic susceptibility from lower to higher than that of water (-9.05 × 10-6). To date, the RBC magnetophoretic motion analyses have been limited to only two quaternary states of the Hb-O2 complexes, fully oxygenated RBCs (i.e. 100 % O2 saturation of Hb inside RBCs) and fully deoxygenated RBCs (0 % O2 saturation of Hb inside RBCs). In this work, the RBC magnetophoretic velocity is measured at small pO2 intervals for the entire physiological range of 0–160 mmHg. The changes in the RBC magnetophoresis as a function of the O2 partial pressure in solution (pO2) agreed with the theoretical predictions based on the RBC-O2 equilibrium curve (OEC, measured by Hemox Analyzer and Blood Oxygen Binding System, BOBS™) and the Adair O2-Hb cooperative binding theory. The results provide a scientific basis for future designs of a “magnetic filter” based on the precise control of the RBC magnetic moment by carefully controlling the pO2 of the RBC suspension.

Shear induced diffusion of platelets revisited.

The transport of platelets in blood is commonly assumed to obey an advection-diffusion equation with a diffusion constant given by the so-called Zydney-Colton theory. Here we reconsider this hypothesis based on experimental observations and numerical simulations including a fully resolved suspension of red blood cells and platelets subject to a shear. We observe that the transport of platelets perpendicular to the flow can be characterized by a non-trivial distribution of velocities with and exponential decreasing bulk, followed by a power law tail. We conclude that such distribution of velocities leads to diffusion of platelets about two orders of magnitude higher than predicted by Zydney-Colton theory. We tested this distribution with a minimal stochastic model of platelets deposition to cover space and time scales similar to our experimental results, and confirm that the exponential-powerlaw distribution of velocities results in a coefficient of diffusion significantly larger than predicted by the Zydney-Colton theory.

Cytoplasmic anion/cation imbalances applied across the membrane capacitance may form a significant component of the resting membrane potential of red blood cells

Electrical aspects of cell function manifest in many ways. The most widely studied is the cell membrane potential, Vm, but others include the conductance and capacitance of the membrane, the conductance of the enclosed cytoplasm, as well as the charge at the cell surface (an electrical double layer) producing an extracellular electrical potential, the ζ-potential. Empirical relationships have been identified between many of these, but not the mechanisms that link them all. Here we examine relationships between Vm and the electrical conductivities of both the cytoplasm and extracellular media, using data from a suspensions of red blood cells. We have identified linear relationships between extracellular medium conductivity, cytoplasm conductivity and Vm. This is in contrast to the standard model of a resting membrane potential which describes a logarithmic relationship between Vm and the concentration of permeable ions in the extracellular medium. The model here suggests that Vm is partially electrostatic in origin, arising from a charge imbalance at an inner electrical double-layer, acting across the membrane and double-layer capacitances to produce a voltage. This model describes an origin for coupling between Vm and ζ, by which cells can alter their electrostatic relationship with their environment, with implications for modulation of membrane ion transport, adhesion of proteins such as antibodies and wider cell–cell interactions.

Flows of healthy and hardened RBC suspensions through a micropillar array.

Red blood cell (RBC) deformability is an important haemorheological factor; it is impaired in many pathologies leading to microvascular complications. Several microfluidic platforms have been utilized to examine the role of deformability in RBC flows but their geometries tend to be simplified. In the present study, we extend our previous work on healthy RBC flows in micropillar arrays [1] to probe the effect of impaired RBC deformability on the velocity and haematocrit distributions in microscale RBC flows. Healthy and artificially hardened RBC suspensions at 25% haematocrit were perfused through the micropillar array at various flow rates and imaged. RBC velocities were determined by Particle Image Velocimetry (PIV) and haematocrit distributions were inferred from the image intensity distributions. The pillars divide the flow into two distinct RBC streams separated by a cell-depleted region along the centreline and in the rear/front stagnation points. RBC deformability was not found to significantly affect the velocity distributions; the shape of the velocity profiles in the interstitial space remained the same for healthy and hardened RBCs. Time-averaged and spatiotemporal intensity distributions, however, reveal differences in the dynamics and local distributions of healthy and hardened cells; hardened cells appear to enter the cell-depleted regions more frequently and their interstitial distributions are more uniform. The study highlights the importance of local RBC distributions and the impact of RBC deformability on cell transport in complex microscale flows.

Conservation of orbital angular momentum and polarization through biological waveguides

A major roadblock to the development of photonic sensors is the scattering associated with many biological systems. We show the conservation of photonic states through optically self-arranged biological waveguides, for the first time, which can be implemented to transmit light through scattering media. The conservation of optical properties of light through biological waveguides allows for the transmission of high bandwidth information with low loss through scattering media. Here, we experimentally demonstrate the conservation of polarization state and orbital angular momentum of light through a self-arranged biological waveguide, several centimeters long, in a sheep red blood cell suspension. We utilize nonlinear optical effects to self-trap cells, which form waveguides at 532 nm and 780 nm wavelengths. Moreover, we use the formed waveguide channels to couple and guide probe beams without altering the information. The formed biological waveguides are in a sub-diffusive scattering regime, so the photons’ information degrades insignificantly over several centimeters of propagation through the scattering media. Our results show the potential of biological waveguides as a methodology for the development of novel photonic biosensors, biomedical devices that require optical wireless communication, and the development of new approaches to noninvasive biomedical imaging.

3D Particle Tracking Velocimetry Applied To Platelet-Size Particles In Red Blood Cells Suspensions Flows Through Squared Microchannels

General defocusing particle tracking (GDPT) method is used to characterize the motion of platelet-size particles within red blood cell (RBC) suspension flows through straight-square microchannels. The method is able to characterize the three-dimensional (3D) nature of particle-RBC interactions, however the measurement depth is limited by the height of the microchannel and hematocrit level (Hct). The RBC mask the particle images and detection becomes impossible above a limit depth. The pressure-driven flow is characterized by velocity distributions and 3D trajectories of platelet-size particles within the RBC suspensions. At large hematocrit levels (Hct=30 %), the velocity distribution exhibits a blunter profile typical of blood flow in capillary-size microchannels. In addition, the interplay between blood viscosity and pressure-driven flow causes the velocity magnitude to decrease, in the center region, with increasing hematocrit. The platelet-size particles exhibit larger velocity fluctuations along the spanwise and vertical directions as Hct is increased, both inside the RBC-rich region and cell-free layer (CFL). On one hand, inside the RBC-rich zone the increasing number of flowing RBC leads to more frequent particle-RBC collisions. On the other hand, even though the particle movement inside the CFL is confined between the boundary of the RBC and the wall of the microchannel, as the thickness of the CFL decreases (i.e. increasing Hct) the collisions with RBC become more frequent. To the authors knowledge, these results represent the first experimental characterization of 3D platelet-size particle behaviour and near-wall dynamics within RBC-suspensions, and it paves the way for more detailed particle-cell flows characterization.

Back Cover: Dielectrophoretic detection of electrical property changes of stored human red blood cells

DOI: 10.1002/elps.202100241 The back cover picture shows our method to measure the electrical properties of human red blood cells (RBCs) subjected to refrigerated storage over a period of 20 days. The RBCs are chemically crosslinked with glutaraldehyde in order to ionically freeze them in their electrical state immediately prior to analysis. As shown, we load a suspension of RBCs into small electrode pinholes. The electrodes are subjected to an electric field and we measure their resulting dielectrophoresis behavior using a 3DEP dielectrophoresis cytometer. Because crosslinked RBCs do not lose their ionic content during analysis, we are able to measure RBC electrical cytoplasm conductivity and membrane conductance changes as cells age in storage.