Department of Physics, Drexel University, Philadelphia, Pennsylvania.
Department of Physics, Drexel University, Philadelphia, Pennsylvania.
Biophys J. 2021 Jun 1;120(11):2138-2147. doi: 10.1016/j.bpj.2021.03.040. Epub 2021 Apr 20.
We have characterized the imbibed horizontal flow of sickle blood into 100-μm-diameter glass capillaries. We find that blood containing sickled cells typically traverses the capillaries between three and four times as slowly as oxygenated cells from the same patient for all genotypes tested, including SS, AS, SC and Sβ thalassemia blood. Blood from SS patients treated with hydroxyurea has a viscosity intermediate between the SS and AA values. Blood containing cells that are not rigidified, such as normal red cells or oxygenated sickle cells, follows a simple Lucas-Washburn flow throughout the length of the 3-cm capillary. By fitting the flexible-cell data to the Lucas-Washburn model, a viscosity can be derived that is in good agreement with previous measurements over a range of volume fractions and is obtained using an apparatus that is far more complex. Deoxygenation sickles and thus rigidifies the cells, and their flow begins as Lucas-Washburn, albeit with higher viscosity than flexible cells. However, the flow further slows as a dense mass of cells forms behind the meniscus and increases in length as flow progresses. By assuming that the dense mass of cells exerts a frictional force proportional to its length, we derive an equation that is formally equivalent to vertical imbibition, even though the flow is horizontal, and this equation reproduces the observed behavior well. We present a simple theory using activity coefficients that accounts for this viscosity and its variation without adjustable parameters. In the course of control experiments, we have found that deoxygenation increases the flexibility of normal human red cells, an observation only recently published for mouse cells and previously unreported for human erythrocytes. Together, these studies form the foundation for an inexpensive and rapid point-of-care device to diagnose sickle cell disease or to determine blood viscosity in resource-challenged settings.
我们已经描述了镰状细胞血液在 100μm 直径玻璃毛细管中的吸入水平流动。我们发现,对于所有测试的基因型,包括 SS、AS、SC 和 Sβ地中海贫血的血液,含镰状细胞的血液的通过速度通常比同一患者的含氧细胞慢三倍到四倍。用羟基脲治疗的 SS 患者的血液的粘度介于 SS 和 AA 值之间。不刚性化的细胞(如正常红细胞或含氧镰状细胞)的血液在整个 3 厘米长的毛细管中遵循简单的 Lucas-Washburn 流动。通过将柔性细胞数据拟合到 Lucas-Washburn 模型中,可以得出与以前在一系列体积分数下的测量值非常吻合的粘度值,并且使用的仪器要复杂得多。脱氧镰状细胞因此使细胞刚性化,其流动开始时类似于 Lucas-Washburn,尽管粘度比柔性细胞高。然而,随着弯月面后面的细胞密集体形成并且随着流动的进行而长度增加,流动进一步减慢。假设密集的细胞群施加的摩擦力与其长度成正比,我们推导出一个方程,该方程在形式上与垂直吸入等效,即使流动是水平的,并且该方程很好地再现了观察到的行为。我们提出了一个简单的理论,该理论使用活度系数来解释这种粘度及其变化,而无需可调参数。在对照实验过程中,我们发现脱氧会增加正常人类红细胞的柔韧性,这一观察结果最近仅在小鼠细胞中发表,以前在人类红细胞中未报告过。这些研究一起为在资源有限的环境中诊断镰状细胞病或确定血液粘度的廉价、快速的即时护理设备奠定了基础。