Assessment of transient changes in oxygen diffusion of single red blood cells using a microfluidic analytical platform

Abstract

Red blood cells (RBCs) capability to deliver oxygen (O2) has been routinely measured by P50. Although this defines the ability of RBCs to carry O2 under equilibrium states, it cannot determine the efficacy of O2 delivery in dynamic blood flow. Here, we developed a microfluidic analytical platform (MAP) that isolates single RBCs for assessing transient changes in their O2 release rate. We found that in vivo (biological) and in vitro (blood storage) aging of RBC could lead to an increase in the O2 release rate, despite a decrease in P50. Rejuvenation of stored RBCs (Day 42), though increased the P50, failed to restore the O2 release rate to basal level (Day 0). The temporal dimension provided at the single-cell level by MAP could shed new insights into the dynamics of O2 delivery in both physiological and pathological conditions.

Erysense, a Lab-on-a-Chip-Based Point-of-Care Device to Evaluate Red Blood Cell Flow Properties With Multiple Clinical Applications

“…After a blood donation, RBCs are separated from plasma, white blood cells, and platelets and stored at 4°C in appropriate buffers for up to 49 days (7 weeks). During this time, RBCs experience the so-called storage lesion, leading to metabolic changes ( Kim-Shapiro et al, 2011 ), oxidative stress to proteins and lipids ( Barshtein et al, 2011 ; Yoshida et al, 2019 ), cell shape ( Doan et al, 2020 ) and oxygen uptake and release modifications ( Chng et al, 2021 ). The morphological changes ( Tinmouth et al, 2006 ; Moon et al, 2021 ; Park et al, 2021 ) and the decrease in deformability as a part of the storage lesion ( Bennett-Guerrero et al, 2007 ; D’Alessandro et al, 2015 ; Matthews et al, 2015 ), result in an alteration of RBC flow behavior and a reduced microcapillary perfusion rate ( Piety et al, 2021 ).…”

Biophysical chemistry behind sickle cell anemia and the mechanism of voxelotor action

“…The exact mechanism by which protons (H + ) facilitate the HbS polymerization to cause a lowering in oxygen affinity at low pH is not known 39 . Moreover, the decrease in hemoglobin affinity for oxygen caused by the accumulation of 2,3-DPG (2,3-diphosphoglycerate) has also been found to correlate with pH 10 , 40 . This mechanism for the intracellular accumulation of 2,3-DPG (2,3-diphosphoglycerate) increases oxygen release from RBCs under circumstances where it is needed most 41 .…”

Structured surface wetting of a PTFE flow-cell for terahertz spectroscopy of proteins

“…For example, while THz spectra of single concentrations of oxy and deoxy-hemoglobin do not show any fine spectral features in absorption in the THz band [15], changes in structure of globular proteins are detectable with THz spectroscopy by studying the effect of the macromolecule on the surrounding hydrogen bond network [16]. Differences in hydration dynamics between the two states of hemoglobin have been observed with microwave radiation [17], however, by using THz radiation instead, and by flowing oxygen and nitrogen gases adjacent to the protein solution (oxygenating and de-oxygenating the protein respectively [18,19]), the investigation of longer-range influences can be made with protein modification occurring in situ. Hemoglobin's function to flexibly bind and relinquish oxygen is coupled with the surrounding water network, and further investigation into its mechanism may provide greater insight into a wide range of hemoglobin disorders [20].…”