Heparin has a variety of pharmacological uses, including applications for anti-tumor metastasis, anti-inflammatory and anti-viral activities and is widely used as a clinical anticoagulant. Due to its widespread applications in the clinical procedures, monitoring heparin levels is critically important to ensure the safe use of heparin and to prevent overdose and complications, such as hemorrhage and thrombocytopenia. However, traditional heparin detection relies on the measurements of the activated clotting time or activated partial thromboplastin time, which are not sufficiently reliable or accurate measurements for certain clinical settings. In this work, we describe a dumbbell probe-aided strategy for ultrasensitive and isothermal detection of heparin based on a uniquely strong protamine–heparin interaction and rolling circle amplification driven signal amplification. The detection limit for heparin is 12.5 ng mL⁻¹ (0.83 nM), which is much lower than the therapeutic level of heparin in cardiovascular surgery (17–67 μM) and in postoperative and long-term treatment (1.7–10 μM). Additionally, the proposed sensing platform works well for heparin monitoring in human plasma samples. This simple and ultrasensitive heparin biosensor has potential application in diagnostics, therapeutics, and in biological research.

中文翻译：

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基于滚环扩增的肝素超灵敏检测平台

肝素具有多种药理用途，包括抗肿瘤转移、抗炎和抗病毒活性，并广泛用作临床抗凝剂。由于其在临床操作中的广泛应用，监测肝素水平对于确保肝素的安全使用并防止过量和并发症（例如出血和血小板减少症）至关重要。然而，传统的肝素检测依赖于活化凝血时间或活化部分凝血活酶时间的测量，这对于某些临床环境来说不是足够可靠或准确的测量。在这项工作中，我们描述了一种基于独特的强鱼精蛋白-肝素相互作用和滚环放大驱动信号放大的肝素超灵敏和等温检测的哑铃探针辅助策略。肝素的检测限为12.5 ng mL ^-1 (0.83 nM)，远低于心血管手术中肝素的治疗水平(17-67 μM)以及术后和长期治疗(1.7-10 μM)。此外，所提出的传感平台非常适合人体血浆样本中的肝素监测。这种简单且超灵敏的肝素生物传感器在诊断、治疗和生物研究中具有潜在的应用。