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在人体体液中以皮摩尔级检测肌酐,具有扩展的线性动态范围,用于肾功能障碍的诊断。

Electrochemical detection of creatinine at picomolar scale with an extended linear dynamic range in human body fluids for diagnosis of kidney dysfunction.

作者信息

Khursheed Sanya, Sarwar Sumera, Hussain Dilshad, Shah Muhammad Raza, Barek Jiri, Malik Muhammad Imran

机构信息

Third World Center for Science and Technology, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi, 75270, Pakistan.

H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi, 75270, Pakistan.

出版信息

Anal Chim Acta. 2025 Jun 1;1353:343978. doi: 10.1016/j.aca.2025.343978. Epub 2025 Mar 27.

Abstract

BACKGROUND

Creatinine levels in different body fluids can serve as an important biomarker for kidney functioning relevant to prostate cancer and chronic kidney disease (CKD). Creatinine levels vary in concentration in different body fluids, such as blood, urine, and saliva. Unlike previously reported sensors, the developed creatinine sensor can be employed for all levels of creatinine in samples of real patients.

RESULTS

In this study, an efficient voltammetric sensor for creatinine is developed by modifying a glassy carbon electrode (GCE) with poly (ethyleneimine) (PEI) capped silver nanoparticles at titanium dioxide (PEI-AgNPs)/TiO, i.e., titanium dioxide (TiO)/graphene oxide (GO) nanocomposites (Ag@GO/TiO-GCE). The Ag@GO/TiO nanocomposite was characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), thermal gravimetric analysis (TGA), X-ray diffraction (XRD), transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential, Fourier transform infrared (FT-IR) spectroscopy, and UV-Vis spectrophotometry. Various voltammetric techniques namely cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), chronoamperometry (CA), and differential pulse voltammetry (DPV) were employed. The Ag@GO/TiO-GCE demonstrated good selectivity, stability, and a quick response time of 1.0 s for creatinine. An extended linear dynamic range (LDR) of creatinine from 0.01 pM (DPV) to 1.0 M (CV) based on different voltammetric techniques is imperative for detecting diverse creatinine levels in various body fluids. The LOD and LOQ of the developed creatinine detection method were found to be 1.15 pM and 3.5 pM, respectively. The electrochemical sensor exhibited an exceptionally high sensitivity of 15.74 μApMcm.The body fluids from healthy volunteers were spiked with a known amount of creatinine to evaluate sensor efficiency in the context of recovery. Finally, blood serum, saliva, and urine samples of kidney patients were analyzed for creatinine levels.

SIGNIFICANCE

An important merit of the developed creatinine sensor is its ability for non-invasive point-of-care diagnosis in saliva with more than 90 % recovery. The comparison of the developed method with the standard Jaffes' colorimetric method endorsed its reliability and extended ability for the samples where Jaffes' method fails. The low LOD, high sensitivity, extended LDR, and low-cost render the possibility of adopting this method for point-of-care diagnosis.

摘要

背景

不同体液中的肌酐水平可作为与前列腺癌和慢性肾脏病(CKD)相关的肾功能的重要生物标志物。肌酐在血液、尿液和唾液等不同体液中的浓度各不相同。与先前报道的传感器不同,所开发的肌酐传感器可用于实际患者样本中所有水平的肌酐检测。

结果

在本研究中,通过用聚(乙烯亚胺)(PEI)包覆的银纳米颗粒修饰玻碳电极(GCE),即二氧化钛(TiO)/氧化石墨烯(GO)纳米复合材料(Ag@GO/TiO),开发了一种用于肌酐检测的高效伏安传感器(Ag@GO/TiO-GCE)。通过扫描电子显微镜(SEM)、原子力显微镜(AFM)、热重分析(TGA)、X射线衍射(XRD)、透射电子显微镜(TEM)、动态光散射(DLS)、zeta电位、傅里叶变换红外(FT-IR)光谱和紫外可见分光光度法对Ag@GO/TiO纳米复合材料进行了表征。采用了多种伏安技术,即循环伏安法(CV)、电化学阻抗谱(EIS)、计时电流法(CA)和差分脉冲伏安法(DPV)。Ag@GO/TiO-GCE对肌酐表现出良好的选择性、稳定性,响应时间快,为1.0秒。基于不同伏安技术,肌酐的线性动态范围(LDR)从0.01 pM(DPV)扩展到1.0 M(CV),这对于检测各种体液中不同水平的肌酐至关重要。所开发肌酐检测方法的检测限(LOD)和定量限(LOQ)分别为1.15 pM和3.5 pM。该电化学传感器表现出15.74 μApMcm的超高灵敏度。向健康志愿者的体液中加入已知量的肌酐,以评估传感器在回收率方面的效率。最后分析了肾病患者的血清、唾液和尿液样本中的肌酐水平。

意义

所开发的肌酐传感器的一个重要优点是其能够在唾液中进行无创即时诊断,回收率超过90%。将所开发的方法与标准的杰氏比色法进行比较,证实了其可靠性以及在杰氏法不适用的样本中的扩展应用能力。低检测限、高灵敏度以及扩展后的线性动态范围和低成本使得该方法有可能用于即时诊断。

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