Electrochemical Creatinine (Bio)Sensors for Point-of-Care Diagnosis of Renal Malfunction and Chronic Kidney Disorders

Abstract

In the post-pandemic era, point-of-care (POC) diagnosis of diseases is an important research frontier. Modern portable electrochemical (bio)sensors enable the design of POC diagnostics for the identification of diseases and regular healthcare monitoring. Herein, we present a critical review of the electrochemical creatinine (bio)sensors. These sensors either make use of biological receptors such as enzymes or employ synthetic responsive materials, which provide a sensitive interface for creatinine-specific interactions. The characteristics of different receptors and electrochemical devices are discussed, along with their limitations. The major challenges in the development of affordable and deliverable creatinine diagnostics and the drawbacks of enzymatic and enzymeless electrochemical biosensors are elaborated, especially considering their analytical performance parameters. These revolutionary devices have potential biomedical applications ranging from early POC diagnosis of chronic kidney disease (CKD) and other kidney-related illnesses to routine monitoring of creatinine in elderly and at-risk humans.

Keywords: biosensors; creatinine; diagnostics; kidney failure; point-of-care.

Figure 1

(a) A schematic representation of the molecular structure of creatinine: 2-amino-1-methyl-2-imidazoline-4-one. (b) The reversible enzymatic conversion of creatine-to-creatine phosphate by creatine kinase and the non-enzymatic production of creatinine from creatine phosphate by the removal of inorganic phosphate and a water molecule. (ATP: adenosine triphosphate; ADP: adenosine diphosphate; Pi: inorganic phosphate).

Figure 2

Principle of the electrochemical recognition of 1-methylhydantoin produced by enzymatic hydrolysis of creatinine and detected by complexation with Co²⁺ ions to produce a redox signal: (a) in the absence of the analyte, and (b) in the presence of the analyte. Reprinted from Dasgupta et al. [28], American Chemical Society (2020).

Figure 3

A schematic representation of a non-enzymatic creatinine sensor: A bare pre-treated screen-printed carbon electrode (PTSPCE) and electrodeposition of Cu nanoparticles (CuNPs); electrochemical impedance spectra of PTSPCE before and after CuNPs electrodeposition; and a cyclic voltammogram showing the non-enzymatic detection of creatinine. Reprinted from Domínguez-Aragón et al. [41], MDPI (Basel, Switzerland) (2023).

Figure 4

The principle of different electrochemical (bio)sensors: A combination of receptors, working electrodes, electrochemical detectors, and methods employed for creatinine diagnosis.

Figure 5

(a,b) HRTEM (high-resolution transmission electron microscopy) images of SnO₂@Cu₂O hybrid electrodes; (c) SAED (selected area electron diffraction) pattern of SnO₂@Cu₂O hybrid nanostructures; (d) amperometric sensor response of SnO₂@Cu₂O nanostructures toward different concentrations of creatinine; and (e) the analytical curve between current density and creatinine concentrations for calculating sensitivity. Adapted from Ullah et al. [65], American Chemical Society (2022).

Figure 6

(a) Working mechanism underlying the all-solid-state creatinine biosensors. The responses of the electrodes prepared with FAPQ (NMP) and FAA (n-propanol) at 4 wt.% are displayed for increasing creatinine concentrations in (b) PB and (c) 0.01 M KCl backgrounds. NH₄⁺SM—ammonium-selective membrane; AEM—anion-exchange membrane; PB—phosphate buffer; FU—Fumion-based membranes. The numbers in the plots indicate the logarithmic concentrations of creatinine. Adapted from Liu et al. [78], American Chemical Society (2020).

Figure 7

(a) Cyclic voltammetric response of SB3C16@Cu₂O/SPCE to 10–200 μM creatinine, showing an inversely proportional relationship between the oxidative peak current and creatinine concentration. (b) Schematic of the proposed sensing mechanism, depicting the specificity imparted by the pseudo-PEM and sensitivity due to the potential-assisted soluble Cu(II)-creatinine complex formation. (c) The Nyquist plot confirms the decrease in the R_ct value of the Cu₂O nanoparticle-modified SPCE post-creatinine quantification, indicating an increase in the overall electrode conductivity. SB3C16: N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate; SPCE: screen-printed carbon electrodes. Reprinted from Kumar et al. [89], American Chemical Society (2023).