A Nanoscale Tool for Photoacoustic-Based Measurements of Clotting Time and Therapeutic Drug Monitoring of Heparin.
A Nanoscale Tool for Photoacoustic-Based Measurements of Clotting Time and Therapeutic Drug Monitoring of Heparin.
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DOI：
10.1021/acs.nanolett.6b02557
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发表时间：
2016-10-12
期刊：
影响因子：
10.8
通讯作者：
Jokerst JV
中科院分区：
文献类型：
--
作者：
Wang J;Chen F;Arconada-Alvarez SJ;Hartanto J;Yap LP;Park R;Wang F;Vorobyova I;Dagliyan G;Conti PS;Jokerst JV
肝素抗凝治疗是临床护理不可或缺的特征，但治疗窗较窄，是第二常见的重症监护室（ICU）用药错误。活性部分凝血活酶时间（aPTT）监测肝素，但存在周转时间长、参考范围可变、低分子量肝素效用有限以及与剂量相关性差等问题。在这里，我们描述了一种光声成像技术，以监测肝素浓度使用亚甲蓝作为一种简单的和联邦药物管理局批准的造影剂。我们发现肝素浓度和在磷酸盐缓冲盐水（PBS）和血液中测量的光声信号之间有很强的相关性。在32 s内检测到血液中的临床相关肝素浓度，检测限为0.28 U/mL。我们通过与aPTT（Pearson's r = 0.86; p < 0.05）以及与硫酸鱼精蛋白治疗的相关性来验证这种成像方法。该技术对低分子量肝素（依诺肝素）也具有良好的实用性，包括72 μg/mL的血液检测限。然后，我们使用这些发现来创建一种基于纳米颗粒的混合材料，该混合材料可以将亚甲基蓝作为可穿戴/植入式肝素传感器的潜在应用，以维持治疗窗口中的药物水平。据我们所知，这是第一次使用光声成像抗凝治疗，具有显着的潜在影响，心血管和外科界。
Heparin anticoagulation therapy is an indispensable feature of clinical care yet has a narrow therapeutic window and is the second most common intensive care unit (ICU) medication error. The active partial thromboplastin time (aPTT) monitors heparin but suffers from long turnaround times, a variable reference range, limited utility with low molecular weight heparin, and poor correlation to dose. Here, we describe a photoacoustic imaging technique to monitor heparin concentration using methylene blue as a simple and Federal Drug Administration-approved contrast agent. We found a strong correlation between heparin concentration and photoacoustic signal measured in phosphate buffered saline (PBS) and blood. Clinically relevant heparin concentrations were detected in blood in 32 s with a detection limit of 0.28 U/mL. We validated this imaging approach by correlation to the aPTT (Pearson’s r = 0.86; p < 0.05) as well as with protamine sulfate treatment. This technique also has good utility with low molecular weight heparin (enoxaparin) including a blood detection limit of 72 μg/mL. We then used these findings to create a nanoparticle-based hybrid material that can immobilize methylene blue for potential applications as a wearable/implantable heparin sensor to maintain drug levels in the therapeutic window. To the best of our knowledge, this is the first use of photoacoustics to image anticoagulation therapy with significant potential implications to the cardiovascular and surgical community.
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作者：
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DOI：
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