Simultaneous quantification of blood rheology and oxygen saturation to evaluate affinity-modifying therapies in sickle cell disease. Issue 21 (22nd September 2022)

• Record Type: Journal Article
• Authors: Hansen, Scott; Wood, David K.
• Is Part Of: Lab on a chip. Volume 22:Issue 21(2022)
• Page Start: 4141
• Page End: 4150
• Publication Date: 2022-09-22
• Subjects: Miniature electronic equipment -- Periodicals; Combinatorial chemistry -- Periodicals; Biotechnology -- Periodicals; 543.0813
• DOI: 10.1039/d2lc00623e
• Languages: English
• ISSNs: 1473-0197

Abstract

Abstract : Sickle cell blood flow and hemoglobin oxygen saturation can be simultaneously measured using a microfluidic device. This combined measurement platform provides a tool to evaluate the potential clinical benefit of anti-sickling therapies. Abstract : Sickle cell blood demonstrates oxygen-dependent flow behavior as a result of HbS polymerization during hypoxia, and these rheological changes provide a biophysical metric that can be used to quantify the pathological behavior of the blood. Relating these rheological changes directly to hemoglobin oxygen saturation would improve our understanding of SCD pathogenesis and the potential effects of therapeutic drugs. Towards this end, we have developed a microfluidic platform capable of spectrophotometric quantification of Hb-O2 saturation and simultaneous evaluation of the accompanying rheological changes in SCD blood flow. We demonstrated the ability to measure changes in Hb-O2 affinity and a restoration of oxygen-independent blood flow behavior after incubation with voxelotor, an oxygen affinity modifying drug approved for use in SCD. We also identified regimes in Hb-O2 saturation where the effects of HbS polymerization begin to take effect in contributing to pathological flow behavior, independent of voxelotor treatment. In contrast, incubation with voxelotor recovered oxygen-dependent blood flow over a range of P O2, providing a framework for understanding voxelotor's therapeutic effect in lowering the P O2 at which the requisite Hb-O2 saturation is reached to observe pathological blood flow. These results help explain the mechanistic effects of voxelotor and show the potential of this platform to identify affinity-modifying compounds and evaluate their therapeutic effect on blood flow.