Red blood cells (RBCs) become sickle-shaped and stiff under hypoxia as a consequence of hemoglobin (Hb) polymerization in sickle cell anemia. Distinguishing between sickle cell disease and trait is crucial during the diagnosis of sickle cell disease. While genetic analysis or high-performance liquid chromatography (HPLC) can accurately differentiate between these two genotypes, these tests are unsuitable for field use. Here, we report a novel microscopy-based diagnostic test called ShapeDx™ to distinguish between disease and trait blood in less than 1 h. This is achieved by mixing an unknown blood sample with low and high concentrations of a chemical oxygen scavenger and thereby subjecting the blood to slow and fast hypoxia, respectively. The different rates of Hb polymerization resulting from slow and fast hypoxia lead to two distinct RBC shape distributions in the same blood sample, which allows us to identify it as healthy, trait, or disease. The controlled hypoxic environment necessary for differential Hb polymerization is generated using an imaging microchamber, which also reduces the sickling time of trait blood from several hours to just 30 min. In a single-blinded proof-of-concept study conducted on a small cohort of clinical samples, the results of the ShapeDx™ test were 100% concordant with HPLC results. Additionally, our field studies have demonstrated that ShapeDx™ is the first reported microscopy test capable of distinguishing between sickle cell disease and trait samples in resource-limited settings with the same accuracy as a gold standard test.

中文翻译：

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对缺氧的不同敏感性可以在护理点对镰状细胞病和特征血样进行基于形状的分类

镰状细胞性贫血中血红蛋白 (Hb) 聚合，导致红细胞 (RBC) 在缺氧条件下变成镰刀状且僵硬。在镰状细胞病的诊断过程中，区分镰状细胞病和性状至关重要。虽然遗传分析或高效液相色谱 (HPLC) 可以准确地区分这两种基因型，但这些测试不适合现场使用。在这里，我们报告了一种名为 ShapeDx™ 的新型基于显微镜的诊断测试，可在不到 1 小时的时间内区分疾病和特征血液。这是通过将未知的血液样本与低浓度和高浓度的化学除氧剂混合，从而分别使血液缓慢和快速缺氧来实现的。缓慢和快速缺氧导致的血红蛋白聚合速率不同，导致同一血液样本中出现两种不同的红细胞形状分布，这使我们能够将其识别为健康、性状或疾病。使用成像微室生成差异 Hb 聚合所需的受控低氧环境，这也将特征血液的镰刀化时间从几个小时缩短到仅 30 分钟。在对一小批临床样本进行的单盲概念验证研究中，ShapeDx™ 测试的结果与 HPLC 结果 100% 一致。此外，我们的实地研究表明，ShapeDx™ 是第一个报道的显微镜测试，能够在资源有限的环境中区分镰状细胞病和性状样本，其准确性与金标准测试相同。