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

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)/TiO₂, i.e., titanium dioxide (TiO₂)/graphene oxide (GO) nanocomposites (Ag@GO/TiO₂-GCE). The Ag@GO/TiO₂ 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/TiO₂-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 μApM⁻¹cm⁻².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.