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Nanomechanical clinical coagulation diagnostics and monitoring of therapies
Nanoscale ( IF 6.7 ) Pub Date : 2017-10-24 00:00:00 , DOI: 10.1039/c7nr06992h
Francesco Padovani 1, 2, 3, 4 , James Duffy 1, 2, 3, 4 , Martin Hegner 1, 2, 3, 4
Affiliation  

Clinical coagulation diagnostics often requires multiple tests. Coagulation times are a first indication of an abnormal coagulation process, such as a coagulation factor deficiency. To determine the specific deficient factor, additional immuno- and/or enzyme assays are necessary. Currently, every clinical laboratory has to normalize their assays (international normalized ratio, INR), and therefore, certain variability within the clinical analytics exists. We report a novel strategy for a quick, reliable and quantitative diagnosis of blood coagulation diseases (e.g. haemophilia) and for monitoring factor replacement and anticoagulant therapies (e.g. heparin treatment). We exploit nano-oscillations of microcantilevers for real-time measurements of the evolving blood plasma clot strength (viscosity). The sensors are oscillated at multiple high resonance mode numbers, in order to minimise the oscillation amplitude (a few nanometers), to provide direct internal control and to increase the quality factor. Along with the activated thromboplastin time (aPTT) and prothrombin time (PT) other parameters important for thrombosis diagnostics can be obtained, including the final clot strength and the fibrinolysis time. We demonstrate the dependence of the parameters on factor deficiencies and we diagnose a specific factor deficiency through an integrated and quantitative in situ immunoassay. This approach does not require continuous calibration since it delivers an absolute quantity (clot strength). The low sample volume required (a few μl) and the ability to measure different parameters within the same test (PT, aPTT and global coagulation assay) make the presented technique a versatile point-of-care device for clinical coagulation diagnostics.

中文翻译:

纳米机械临床凝血诊断和治疗监测

临床凝血诊断通常需要进行多次测试。凝血时间是异常凝血过程(例如凝血因子缺乏症)的第一个指示。为了确定特定的缺陷因子,需要额外的免疫和/或酶测定。当前,每个临床实验室都必须对其测定进行归一化(国际标准化比率,INR),因此,临床分析中存在一定的可变性。我们报告了一种快速,可靠和定量诊断凝血疾病(例如血友病)以及监测因子替代和抗凝疗法(例如肝素治疗)。我们利用微悬臂梁的纳米振荡来实时测量不断发展的血浆凝块强度(粘度)。传感器以多个高共振模式编号进行振荡,以最小化振荡幅度(几纳米),以提供直接的内部控制并提高品质因数。连同激活的凝血活酶时间(aPTT)和凝血酶原时间(PT)一起,可以获得对血栓形成诊断很重要的其他参数,包括最终血凝强度和纤维蛋白溶解时间。我们证明了参数对因素缺陷的依赖性,并且我们通过综合和定量的原位诊断了特定的因素缺陷免疫测定。这种方法不需要连续校准,因为它可以提供绝对量(抗粘强度)。所需的低样品量(几微升)和在同一测试(PT,aPTT和整体凝血测定)中测量不同参数的能力使本技术成为用于临床凝血诊断的多功能即时医疗设备。
更新日期:2017-11-23
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