Acute Kidney Injury Detection using Real Human Urine NGAL Biomarker Sensor based on 3D Graphene

Netnapa Sittihakote, Sirirat Anutrakulchai, A. Tuantranont, Pobporn Danvirutai, Chavis Srichan
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Abstract

Acute kidney injury (AKI) is not a specified symptom in the early stages. Frequency of AKI occurrence is highly correlated to Chronic Kidney Disease (CKD). Therefore, development of non-invasive, ultra-sensitive, and highly accurate sensing platform is crucial for early AKI diagnosis. Serum creatinine (SCr) level usually takes 24-72 hours to response to the incident of AKI. Meanwhile, urine Neutrophil Gelatinase-Associated Lipocalin (NGAL) takes only 2 hours to response after the AKI occurrence. In this work, we investigated the use of microporous graphene and dipole-dipole enhancement between graphene/nickel layers to enhance electrode sensitivity for urine NGAL level determination. Selectivity was assured using enzymatic electrochemistry. Once NGAL level was measured, a doctor can diagnose AKI under additional information on patient’s conditions. The result is promising since the detection range was 0.110 to 93.9 ng/ml and the correlation coefficient is 0.8235. The detection covered AKI primary diagnostic cutoff level at 87 ng/ml in urine. The electrochemical immunosensor was able to determine NGAL in Urine with results compared to those provided by the standard ELISA method. This work is a part of development of handheld NGAL determination strip in human urine samples and prepared portable NGAL sensing devices. Despite our investigation’s limitation, the acquired data indicates that non-invasive acute kidney injury detection using actual human urine with graphene foam/nickel-based electrochemical sensor should be further explored as an auxiliary diagnostic tool for AKI.
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基于3D石墨烯的真实人尿NGAL生物标志物传感器检测急性肾损伤
急性肾损伤(AKI)在早期阶段并不是一个特定的症状。AKI的发生频率与慢性肾脏疾病(CKD)高度相关。因此,开发无创、超灵敏、高精度的传感平台对于AKI的早期诊断至关重要。血清肌酐(SCr)水平通常需要24-72小时才能对AKI事件做出反应。同时,尿中性粒细胞明胶酶相关脂钙蛋白(NGAL)在AKI发生后仅需要2小时就能产生反应。在这项工作中,我们研究了使用微孔石墨烯和石墨烯/镍层之间的偶极子-偶极子增强来提高电极对尿液NGAL水平测定的灵敏度。利用酶电化学保证了选择性。一旦测量了NGAL水平,医生就可以根据患者的额外信息诊断AKI。检测范围为0.110 ~ 93.9 ng/ml,相关系数为0.8235,具有良好的应用前景。该检测覆盖了尿中87 ng/ml的AKI初级诊断临界值。电化学免疫传感器能够测定尿液中的NGAL,其结果与标准ELISA方法提供的结果相比较。本工作是开发手持式人体尿液NGAL测定条和制备便携式NGAL传感装置的一部分。尽管我们的研究存在局限性,但所获得的数据表明,应进一步探索利用真实人尿和石墨烯泡沫/镍基电化学传感器进行无创急性肾损伤检测,作为AKI的辅助诊断工具。
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