Differential sensitivity to hypoxia enables shape-based classification of sickle cell disease and trait blood samples at point of care

IF 6.1 2区 医学 Q1 ENGINEERING, BIOMEDICAL Bioengineering & Translational Medicine Pub Date : 2023-12-27 DOI:10.1002/btm2.10643
Claudy D'Costa, Oshin Sharma, Riddha Manna, Minakshi Singh, Samrat Singh, Srushti Singh, Anish Mahto, Pratiksha Govil, Sampath Satti, Ninad Mehendale, Yazdi Italia, Debjani Paul
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Abstract

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.

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对缺氧的不同敏感性可在护理点对镰状细胞疾病和特质血液样本进行基于形状的分类
由于镰状细胞贫血症中血红蛋白(Hb)聚合的结果,红细胞(RBC)在缺氧情况下会变成镰状且僵硬。在诊断镰状细胞病的过程中,区分镰状细胞病和遗传性镰状细胞病至关重要。虽然基因分析或高效液相色谱法(HPLC)可以准确区分这两种基因型,但这些检测方法不适合现场使用。在这里,我们报告了一种名为 ShapeDx™ 的基于显微镜的新型诊断测试,该测试可在 1 小时内区分疾病和特异性血液,其方法是将未知血液样本与低浓度和高浓度的化学氧清除剂混合,从而使血液分别处于慢缺氧和快缺氧状态。缓慢缺氧和快速缺氧导致 Hb 聚合速度不同,从而在同一血液样本中形成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、特质或疾病。差异 Hb 聚合所需的可控缺氧环境是通过成像微室产生的,它还能将特质血液的镰状时间从数小时缩短到 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™ 检测结果与 HPLC 结果的一致性达到 100%。此外,我们的现场研究还表明,ShapeDx™ 是首个报道的显微镜检测方法,能够在资源有限的环境中区分镰状细胞疾病和特质样本,其准确性与金标准检测方法相同。
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来源期刊
Bioengineering & Translational Medicine
Bioengineering & Translational Medicine Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
8.40
自引率
4.10%
发文量
150
审稿时长
12 weeks
期刊介绍: Bioengineering & Translational Medicine, an official, peer-reviewed online open-access journal of the American Institute of Chemical Engineers (AIChE) and the Society for Biological Engineering (SBE), focuses on how chemical and biological engineering approaches drive innovative technologies and solutions that impact clinical practice and commercial healthcare products.
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