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使用生物硫醇可激活化学发光探针进行全血即时检测以辅助诊断肝损伤

Point-of-Care Testing of Whole Blood for Liver Injury Auxiliary Diagnosis with Biothiols Activable Chemiluminescent Probe.

作者信息

Zhu Jingxuan, Xu Shuai, Zhou Lei, Zeng Qin, Wang Yuhan, Yan Mei, Liu Hongwen

机构信息

College of Chemistry and Chemical Engineering, The First Affiliated Hospital of Hunan Normal University, Hunan Normal University, Changsha 410081, P. R. China.

School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, China.

出版信息

Anal Chem. 2024 Jul 16. doi: 10.1021/acs.analchem.4c02831.

Abstract

Liver injury significantly affects a patient's health and quality of life. However, timely and convenient diagnosis of this disease via whole blood detection remains challenging due to the lack of user-friendly and fast readout blood test methods. Herein, we developed such a method for the swift auxiliary diagnosis of liver injury via whole blood detection using a customed point-of-care testing (POCT) system consisting of a biothiols-activatable chemiluminescent probe and a hand-held POCT device. Biothiols served as the target to build the activable chemiluminescence probe due to their abnormal level in liver injury. Compared with fluorescent and electrical POCTs, this method is more convenient and has strong universality. By incorporating cyclodextrin via host-guest chemistry, we intensified chemiluminescence while mitigating chemical hemolysis caused by the dissolution of organic molecules, making this system suitable for whole blood analysis. Preliminary assessments in aqueous solutions, living cells, and mouse models confirmed its sensitivity, reliability, and feasibility. Simply mixing blood with the probe for 30 min yielded a clear signal readout within 15 s on the POCT device. Utilizing this portable detector, the reduced biothiol level was tested in 18 liver injury patient blood samples, and the results were similar to those measured by a commercial kit and in vivo imaging system. Thus, this work provides a universal platform for the fast and convenient detection of other biomarkers in whole blood samples and opens up possibilities for the rapid clinical diagnosis of diseases, enabling patients to conduct home self-examinations with ease.

摘要

肝损伤严重影响患者的健康和生活质量。然而,由于缺乏用户友好且快速读出结果的血液检测方法,通过全血检测对该疾病进行及时、便捷的诊断仍然具有挑战性。在此,我们开发了一种通过全血检测快速辅助诊断肝损伤的方法,该方法使用了一个由生物硫醇可激活化学发光探针和手持式即时检测(POCT)设备组成的定制即时检测系统。由于生物硫醇在肝损伤中的水平异常,因此将其作为构建可激活化学发光探针的靶标。与荧光和电化学POCT相比,该方法更便捷且具有很强的通用性。通过主客体化学引入环糊精,我们增强了化学发光,同时减轻了有机分子溶解引起的化学溶血,使该系统适用于全血分析。在水溶液、活细胞和小鼠模型中的初步评估证实了其灵敏度、可靠性和可行性。只需将血液与探针混合30分钟,即可在POCT设备上于15秒内获得清晰的信号读数。利用这种便携式检测仪,对18例肝损伤患者血液样本中的生物硫醇水平降低情况进行了检测,结果与商业试剂盒和体内成像系统测量的结果相似。因此,这项工作为全血样本中其他生物标志物的快速便捷检测提供了一个通用平台,并为疾病的快速临床诊断开辟了可能性,使患者能够轻松地进行家庭自我检测。

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