Department of NanoEngineering, University of California San Diego, La Jolla, CA 92093, United States.
Cardiology Unit, VA Healthcare System, San Diego, La Jolla, CA 92161, United States.
Biosens Bioelectron. 2019 Feb 1;126:831-837. doi: 10.1016/j.bios.2018.11.052. Epub 2018 Dec 8.
Heparin is an indispensable drug in anticoagulation therapy but with a narrow therapeutic window, which dictates regular testing and dose adjustment. However, current monitoring tools have a long turnaround time or are operator intensive. In this work, we describe a cellulose-based photoacoustic sensor for heparin. The sensors have a turnaround time of 6 min for whole blood samples and 3 min for plasma samples regardless of heparin concentration. These sensors have a limit of detection of 0.28 U/ml heparin in human plasma and 0.29 U/ml in whole blood with a linear response (Pearson's r = 0.99) from 0 to 2 U/ml heparin in plasma and blood samples. The relative standard deviation was < 12.5% in plasma and < 17.5% in whole blood. This approach was validated with heparin-spiked whole human blood and had a linear correlation with the activated partial thromboplastin time (aPTT) (r = 0.99). We then studied 16 sets of clinical samples-these had a linear correlation with the activated clotting time (ACT) (Pearson's r = 0.86, P < 0.0001). The photoacoustic signal was also validated against the cumulative heparin dose (Pearson's r = 0.71, P < 0.0001). This approach could have applications in bed-side heparin assays for continuous heparin monitoring.
肝素是抗凝治疗中不可或缺的药物,但治疗窗较窄,这就需要定期检测和剂量调整。然而,目前的监测工具检测时间长或需要操作人员投入大量精力。在这项工作中,我们描述了一种基于纤维素的肝素光声传感器。无论肝素浓度如何,这些传感器对全血样本的检测时间均为 6 分钟,对血浆样本的检测时间均为 3 分钟。这些传感器对人血浆中的肝素检测限为 0.28 U/ml,对全血中的肝素检测限为 0.29 U/ml,在血浆和全血中,肝素浓度在 0 至 2 U/ml 范围内呈线性响应(Pearson r = 0.99)。在血浆中的相对标准偏差小于 12.5%,在全血中的相对标准偏差小于 17.5%。该方法用肝素加标全血进行了验证,与激活部分凝血活酶时间(aPTT)呈线性相关(r = 0.99)。然后,我们研究了 16 组临床样本-这些样本与激活凝血时间(ACT)呈线性相关(Pearson r = 0.86,P < 0.0001)。光声信号也与累积肝素剂量呈相关性(Pearson r = 0.71,P < 0.0001)。这种方法可能在床边肝素检测中用于连续肝素监测。