Creatinine Sensor Research Articles

Fabrication and Characterization of a Creatinine Sensor using Differential Extended-Gate Field Effect Transistors

Fabrication and Characterization of a Creatinine Sensor using Differential Extended-Gate Field Effect Transistors

High-Performance Electrochemical Creatinine Sensors Based on β-Lead Dioxide/Single-Walled Carbon Nanotube Electrodes.

Creatinine is an important biomarker of kidney function and muscular metabolism. In this paper, we developed the β-lead dioxide/single-walled carbon nanotube (β-PbO2/CNT) and the β-PbO2/CNT ion-selective electrode (β-PbO2/CNT/ISE), which were used as highly sensitive potentiometric sensors for creatinine detection. The fabricated electrodes exhibited highly pH-sensitive characteristics due to the synergistic effect of the electrochemical properties of CNT and β-PbO2. Moreover, an ammonium-ion-selective membrane coating allowed the β-PbO2/CNT electrode to be NH4+-selective for direct detection of the ammonium ion. By exploiting the electrochemical characteristics of these electrodes, the creatinine assay was established through the one-step selective conversion of creatinine by creatinine deiminase, in which the OH- and NH4+ generated by the enzymatic reaction were detected using β-PbO2/CNT and β-PbO2/CNT/ISE electrodes as pH- and NH4+-responsive sensors, respectively. The total creatinine assay can be completed within ∼5 min. The assay results from β-PbO2/CNT and β-PbO2/CNT/ISE showed excellent sensitivity values of -75.56 and 64.62 mV in the detection range of 10-400 μM with a fast response (20 s), and the limits of detection were calculated to be 0.06 and 0.13 μM, respectively. Moreover, the developed creatinine sensor showed high selectivity against 11 interfering bio/chemical species with negligible interferences (selectivity coefficient <10-4) and excellent repeatability (>97% within 25 cycles) and long-term stability for 4 weeks of storage. In addition, the feasibility and practicality of the device were successfully demonstrated in human serum tests, with recoveries of 95-104% for PbO2/CNT and 92-110% for PbO2/CNT/ISE.

High aspect ratio copper nanowires modified screen-printed carbon electrode for interference-free non-enzymatic detection of serum creatinine in neutral medium

In this work, the affinity of copper to create a soluble coordination complex with creatinine was exploited for the electrochemical detection of creatinine levels in serum. High aspect ratio copper nanowires were synthesized by controlled hydrothermal method in the presence of dextrose and octadecyl amine. Disposable screen-printed electrode modified with copper nanowires demonstrated excellent sensing towards creatinine in 0.1 M phosphate buffer with a wide detection range of 50–500 µM. The developed sensor was found to be highly selective even in the presence of interfering molecules like glucose, ascorbic acid, urea, uric acid, and chloride. The proposed copper nanowire-based non-enzymatic creatinine sensor is highly promising for point-of-care testing applications.

Deciphering the complexation processes of creatinine-cobalt and creatinine-cobalt-2-nitrobenzaldehyde: Morphological, spectroscopic and electrochemical analysis

Owing to creatinine's coordinating property with transition metal ions, its oxidation by 2-nitrobenzaldehyde, and the ability of the nitrite group to form chelate and bridging compounds with cobalt ions, different conditions-dependent pathways of reactions can be undertaken when any two of the three components (cobalt ion, creatinine, and 2-nitrobenzaldehyde) react. Bringing these three components together opens up multiple reaction possibilities. In this work, the effect of 2-nitrobenzaldehyde on a new complexation pathway of creatinine-cobalt has been explored, under some controlled conditions. As a result, a 4-coordinated complex, [Co(CR)3(H2O)]Cl2, and a 7-coordinated complex, [Co(CR)3(H2O)2(2-NBA)]Cl3, were obtained, where CR= creatinine and 2-NBA= 2-nitrobenzaldehyde. P-XRD analysis confirmed the formation of new amorphous complexes and SEM analysis revealed their rod-shaped and nano-fibrous morphologies respectively. FTIR and Raman analysis established the coordination of cobalt ions with endocyclic nitrogen of creatinine and chelation with the nitro group of 2-NBA. From EDX analysis, close similarities between the experimental and theoretical elemental compositions of the complexes were determined. EPR analysis established the paramagnetic nature of the complexes. While DRS studies indicated different d-configurations of the cobalt ions in the complexes, CV and DPV confirmed their respective oxidation states to be +2 and +3. The coordination pathways described here can be put into a creatinine sensor development application.

Harnessing quantum plexcitons for enhanced sensitivity and selectivity of creatinine sensor

Despite their widespread usage, surface plasmon resonance (SPR) sensors have several drawbacks, including limited sensitivity and the requirement for sophisticated functionalization chemistry to enhance their performance. In contrast, using quantum states for sensing may result in an enormous increase in sensor performance. These states, however, often need a rigorously controlled environment, which limits their adoption. Recently, there has been a surge of interest in employing quantum plexcitons to solve this conundrum, which has recently been proven to be resilient and robust even in ambient conditions. Here, we report the utilization of plexcitons induced through hybridization of surface plasmon and excitons in a SPR-Otto configuration for sensing creatinine molecules. Using an organic pentamer, BOBzBT2, the ultra-strong coupling regime with a Rabi splitting of 22 % of the uncoupled energy was observed and exploited to monitor the creatinine concentrations. This demonstration proposes a way to combine the benefits of an SPR-based design with the sensitivity offered by quantum plexcitons, which is beneficial for future practical quantum sensing.

Sol-gel synthesized RexBi1-x-O thin films for electrochemical creatinine sensing: A facile fabrication approach

The escalating predominance of renal diseases has obliged vigorous research on developing efficient and cost-effective biosensors for creatinine, an aspirant biomarker reflecting renal health. Herein, we fabricated a highly sensitive and selective Rhenium (Re)-doped Bismuth oxide (Bi2O3) (RexBi1-x-O) based enzymatic electrochemical creatinine biosensor. Various concentrations of Re (5%, 10%, and 20%) were mixed with Bi2O3 solution via facile sol-gel synthesis and deposited on an Indium Tin oxide (ITO) substrate. The detailed physicochemical and electrochemical performance of the thin film was investigated and compared at different annealing temperatures (400 °C, 500 °C, and 600 °C). The optimized RexBi1-x-O thin film (Re0.10Bi0.90-O at 500 °C annealing temperature) depicted a limit of detection (LOD) as low as 28 μM in a concentration range of 0.05 mM–2 mM with excellent selectivity. To ensure the feasibility of the proposed creatinine sensor, its sensing performance was verified in human serum contaminated with altered creatinine concentrations, which manifested a satisfactory recovery rate. Eventually, the outstanding performance of RexBi1-x-O-based enzymatic creatinine sensor indorsed it as an accountable candidate for even more complex markers detection.

Rapid electrodeposition of Cu nanoparticle film on Ni foam as an integrated 3D free-standing electrode for non-invasive and non-enzymatic creatinine sensing.

High cost, inherent destabilization, and intricate fixing of enzyme molecules are the main drawbacks of enzyme-based creatinine sensors. The design of a low-cost, stabilizable, and enzyme-free creatinine sensing probe is essential to address these limitations. In this work, an integrated three-dimensional (3D) free-standing electrode was designed to serve as a non-enzymatic creatinine sensing platform and was fabricated by rapid electrodeposition of a dense copper nanoparticle film on nickel foam (Cu NP film/NF). This low-cost, stable, easy-to-fabricate, and binder-free Cu NP film/NF electrode has abundant active sites and excellent electrochemical performance. Cyclic voltammetry measurements show a wide linear range (0.25-24 mM), low detection limit (0.17 mM), and high sensitivity (306 μA mM-1 cm-2). The developed sensor shows high recovery of creatinine concentration in real urine. Besides, it has better specificity, reproducibility, and robustness in detecting creatinine. These excellent results suggest that a non-enzymatic creatinine sensor based on an integrated 3D free-standing Cu NP film/NF electrode has good potential for non-invasive detection of urinary creatinine.

A fast and highly selective ECL creatinine sensor for diagnosis of chronic kidney disease

A new ECL sensor to monitor creatinine as a biomarker for diagnosis of chronic kidney diseases.

A flexible capacity-metric creatinine sensor based on polygon-shape polyvinylpyrrolidone/CuO and Fe2O3 NRDs electrodeposited on three-dimensional TiO2–V2O5–Polypyrrole nanocomposite

The innovations of the present work include these items; (i) Design and preparation of three-dimensional flexible conductive polymeric nanocomposites (3D-FCPNCs) containing polypyrrole (PPy), V2O5 and TiO2 and modification of their surface with polygon-shape polyvinylpyrrolidone/CuO nanorods (PVP/CuO NRDs) and Fe2O3 NRDs using an hierarchical process based on isoelectric point (IEP), (ii) Application of the prepared surfaces as the flexible enzymeless creatinine sensors using four calibration curves (impedimetric, real capacitance (C′), imaginary capacitance (C″) and double layer capacitance (Cdl)) obtained from electrochemical impedance spectroscopy (EIS) technique. The best results have been obtained using PVP/CuO NRDs–Fe2O3 NRDs/TiO2–V2O5–PPy 3D-FCPNC hierarchical electrode with a wide range of the linear concentration range (10 nmol L−1 −1.3 mmol L−1). Although, determination of creatinine through extraction of parameters such as charge transfer resistance (Rct) and Cdl from measuring impedance at a wide range of frequencies provides useful information about the characteristics of the electrolyte/electrode interface, but measuring real and imaginary capacitances at a specific frequency instead of a wide frequency range can decrease the response time to lower than 1 min. Finally, the prepared hierarchical enzymeless sensors have been successfully used to estimate creatinine concentration in blood serum.

An alkaline ferrocyanide non-enzymatic electrochemical sensor for creatinine detection

Creatinine is a useful metabolite for the evaluation of Chronic Kidney Disease (CKD). Creatinine concentrations in urine outside of the healthy range of 4 to 15 mM may indicate CKD and other kidney conditions. Early detection and monitoring can provide lifesaving intervention, and as such there is a need to develop rapid, cheap and selective electrochemical creatinine sensors. A simple non-enzymatic creatinine sensing platform enabled by the electrocatalytic response of the metabolite to ferricyanide in alkaline conditions is presented. Studies were made on unmodified glassy carbon (GCE) and screen printed carbon electrodes (SPCE), both giving sensitivity of 21 ± 5 µA mM−1 cm−2 and limit of detection of ca. 60 µM.

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

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.

Fabrication of an Enzyme Membrane for Creatinine Detection and Its Application to an Extended-Gate FET-Based Biosensor

An extended-gate field effect transistor (EGFET) based creatinine sensor using an enzyme-containing silk-fibroin membrane successfully fabricated. In this experiment, we used creatinine deiminase as a detection enzyme for serum creatinine, which is known as a marker of chronic kidney disease. The fabricated biosensor showed excellent potentiometric response to creatinine over a wide range from 0.007 - 0.4 mg/mL in phosphate buffer solution, which can enable to measure creatinine concentration in blood plasma.

Non-enzymatic electrochemical detection of creatinine based on a glassy carbon electrode modified with a Pd/Cu2O decorated polypyrrole (PPy) nanocomposite: an analytical approach.

The major constraints of standard enzymatic biosensors are poor long-term storage stability and high cost. Hence, there is extensive research towards fabrication of reliable enzymeless biosensors based on nanomaterials. In this paper, we present the development of an enzymeless electrochemical biosensor for highly precise detection of creatinine. This involves the use of a simple yet effective alternative to the commonly utilized Pd/Cu2O/PPy nanocomposite, which was characterized by different analytical methods. The present electrochemical sensor provides a wide detection range (0.1 to 150 μM), low detection limit (0.05 μM) and high sensitivity (0.207 μA), and is capable of detecting the creatinine level in human urine samples, which are inexpensive. The results are reproducible, and the sensor is stable. The sensor demonstrates good electrocatalytic activity and selectivity towards the detection of creatinine in the presence of various other similar biological entities. When compared to other existing counterparts, the electrocatalytic behaviour of the present sensor is comparable, if not better. So, the present electrochemical sensor for creatinine might be employed as a long-term diagnostic alternative.

Anodic SnO2 Nanoporous Structure Decorated with Cu2O Nanoparticles for Sensitive Detection of Creatinine: Experimental and DFT Study.

Advanced anodic SnO2 nanoporous structures decorated with Cu2O nanoparticles (NPs) were employed for creatinine detection. Anodization of electropolished Sn sheets in 0.3 M aqueous oxalic acid electrolyte under continuous stirring produced complete open top, crack-free, and smooth SnO2 nanoporous structures. Structural analyses confirm the high purity of rutile SnO2 with successful functionalization of Cu2O NPs. Morphological studies revealed the formation of self-organized and highly-ordered SnO2 nanopores, homogeneously decorated with Cu2O NPs. The average diameter of nanopores is ∼35 nm, while the average Cu2O particle size is ∼23 nm. Density functional theory results showed that SnO2@Cu2O hybrid nanostructures are energetically favorable for creatinine detection. The hybrid nanostructure electrode exhibited an ultra-high sensitivity of around 24343 μA mM-1 cm-2 with an extremely lower detection limit of ∼0.0023 μM, a fast response time (less than 2 s), and wide linear detection ranges of 2.5-45 μM and 100 μM to 15 mM toward creatinine. This is ascribed to the creation of highly active surface sites as a result of Cu2O NP functionalization, SnO2 band gap diminution, and the formation of heterojunction and Cu(1)/Cu(ll)-creatinine complexes through secondary amines which occur in the creatinine structure. The real-time analysis of creatinine in blood serum by the fabricated electrode evinces the practicability and accuracy of the biosensor with reference to the commercially existing creatinine sensor. The proposed biosensor demonstrated excellent stability, reproducibility, and selectivity, which reflects that the SnO2@Cu2O nanostructure is a promising candidate for the non-enzymatic detection of creatinine.

Low-cost, disposable sensors based on polystyrene waste and V–TiO2 microneedle composites for diagnosis of renal malfunction and muscle dystrophy

A compact, cost-efficient, and disposable electrochemical creatinine sensor is designed using disposable screen-printed carbon electrodes coated with a composite receptor based on polystyrene foam (i.e., packaging material waste) and anatase-phase V–TiO2 microneedles. The electrochemical sensor is capable of monitoring 1–25 μM creatinine in a standard redox solution at 7.4 pH and room temperature. The electrochemical measurements are performed with a portable potentiostat using an android smartphone. Cyclic voltammetry and differential pulse voltammetry characteristics are measured to monitor the concentration of creatinine. The sensor exhibits excellent creatinine sensitivity of 30.95 ± 1.73 μA/cm2⸳μM and an extremely low threshold detection limit of 184 nM creatinine.

Synthesis of Sodium Citrate-Capped Gold Nanoparticles and its Application for Creatinine Detection in Urine Sample by Colorimetric Analysis Based on the Red-Green-Blue (RGB) Digital Image

AuNPs have been synthesized with reducing agents and sodium citrate covering agents using the colorimetric method. The formation of sodium citrate-covered AuNPs was confirmed using a UV-Vis spectrophotometer. The optimization of creatinine concentration of 10 mM was indicated by shifting the absorption peak from 530 to 700 nm. The results of this optimization were then used to standardize the detection of creatinine in urine samples using a validation test method. The TEM results showed that the AuNPs were dispersed at relatively large distances. The size of the AuNPs was 30.67 nm and creatinine was 19.96 nm. This is because no substance had aggregate NPS, therefore, the particles are still scattered. Testing the quantitative value of Red-Green-Blue (RGB) digital images involved a mobile phone camera. The resulting images were stored in a memory card and then transferred to a laptop/computer. The data were processed using ImageJ software. The linear correlation and selectivity of the quantitative values ​​of Red-Green-Blue (RGB) from the RGB method were compared with the results of colorimetric detection using the UV-Vis spectrophotometric method. The data were used to determine the amount of creatinine concentration. The results exhibited that sodium citrate had the ability as a reducing agent and a covering agent in the synthesis of AuNPs for the determination of creatinine. The RGB digital image method had good sensitivity to creatinine with LoD of 0.068 mM dan LoQ of 0.228 mM, which was smaller than the UV-Vis spectrophotometric method where LoD was 0.225 mM and LoQ was 0.751 mM. The validation method results showed that AuNPs can be used as a creatinine sensor. This method used a colorimetric sensor of the Red-Green-Blue (RGB) component in urine samples and was translated with ImageJ software.

Highly Sensitive and Selective Detection of Diabetic Nephropathy Markers by a Perovskite LaNiO3−x Based Potentiometric Sensor

This work describes the fabrication of efficient biosensors to detect diabetic nephropathy markers (pH, glucose, and creatinine) by constructing a layer-wise sol-gel deposited perovskite LaNiO3−x (LNO) thin-film combined with intermedial annealing (500°C to 700°C). The structural, morphological, and compositional properties of LNO were analyzed by X-ray diffraction, Raman spectroscopy, field emission scanning electron microscopy, atomic force microscopy, and X-ray photoelectron spectroscopy. The bilayer-coated LNO thin film annealed at 600°C exhibited the highest pH sensitivity of 65.83 mV pH−1 with 99.36% linearity for pH 2 to pH 12, a minimum hysteresis of 0.6 mV, and an almost unvarying drift rate of 2.04 mV h−1 in an extended gate field effect transistor (EGFET). Furthermore, the optimized film was utilized to detect glucose and creatinine by immobilizing different enzymes on the LNO surface. The glucose sensor was able to detect glucose with a sensitivity of 20.5 mV mM−1, whereas the sensitivity of the creatinine sensor was 126.4 mVpCcreatinine −1 for an acceptable linear range, with high selectivity for their respective target molecules. Hence, an LNO-based EGFET sensor can be considered a decisive solicitant for diagnosing diabetic nephropathy.

ZIF-8 Nanoparticles Based Electrochemical Sensor for Non-Enzymatic Creatinine Detection.

There is a consistent demand for developing highly sensitive, stable, cost-effective, and easy-to-fabricate creatinine sensors as creatinine is a reliable indicator of kidney and muscle-related disorders. Herein, we reported a highly sensitive and selective non-enzymatic electrochemical creatinine sensor via modifying poly(3,4 ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) coated indium tin oxide (ITO) substrate by zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs). The topography, crystallinity, and composition of the sensing electrode were characterized by field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The peroxidase-like activity of ZIF-8 nanoparticles enabled it to detect creatinine forming a zinc-creatinine composite. The electrochemical behavior and sensing performance were evaluated by amperometric and impedimetric analysis. The sensor obtained a sufficiently low limit of detection (LOD) of 30 µM in a clinically acceptable linear range (0.05 mM–2.5 mM). The interference study demonstrated high selectivity of the sensor for creatinine concerning other similar biomolecules. The sensing performance of the creatinine sensor was verified in the actual human serum, which showed excellent recovery rates. Hence, the magnificent performance of ZIF-8 based non-enzymatic creatinine sensor validated it as a responsible entity for other complicated renal markers detection.

Electrochemical creatinine detection for advanced point-of-care sensing devices: a review.

Creatinine is an amino acid derived from creatine catabolism at different steps of the body's organs, and its detection is significant because levels out of normal values are linked to some diseases like kidney failure. Normal concentration levels of creatinine in blood are from 45 to 110 μM, while in urine, typical concentrations range between 3.3 to 27 mM, and in saliva from 8.8 and 26.5 μM. Nowadays, the creatinine detection is carried through different spectroscopic-colorimetric methods; however, the resulting values present errors due to high interferences, delayed analysis, and poor stability. Electrochemical sensors have been an alternative to creatinine detection, and the electrochemical methods have been adapted to detect in enzymatic and non-enzymatic sensors, the latter being more relevant in recent years. Nanomaterials have made creatinine sensors more stable, sensitive, and selective. This review presents recent advances in creatinine electrochemical sensors for advances in point-of-care (POC) sensing devices, comprising both a materials point of view and prototypes for advanced sensing. The effect of the metal, particle size, shape and other morphological and electronic characteristics of nanomaterials are discussed in terms of their impact on the effective detection of creatinine. In addition, the application of nanomaterials in POC devices is revised pointing to practical applications and looking for more straightforward and less expensive devices to manufacture.

Facile Detection of Blood Creatinine Using Binary Copper-Iron Oxide and rGO-Based Nanocomposite on 3D Printed Ag-Electrode under POC Settings.

Metal nanoparticles have been helpful in creatinine sensing technology under point-of-care (POC) settings because of their excellent electrocatalyst properties. However, the behavior of monometallic nanoparticles as electrochemical creatinine sensors showed limitations concerning the current density in the mA/cm2 range and wide detection window, which are essential parameters for the development of a sensor for POC applications. Herein, we report a new sensor, a reduced graphene oxide stabilized binary copper-iron oxide-based nanocomposite on a 3D printed Ag-electrode (Fe-Cu-rGO@Ag) for detecting a wide range of blood creatinine (0.01 to 1000 μM; detection limit 10 nM) in an electrochemical chip with a current density ranging between 0.185 and 1.371 mA/cm2 and sensitivity limit of 1.1 μA μM-1 cm-2 at physiological pH. Interference studies confirmed that the sensor exhibited no interference from analytes like uric acid, urea, dopamine, and glutathione. The sensor response was also evaluated to detect creatinine in human blood samples with high accuracy in less than a minute. The sensing mechanism suggested that the synergistic effects of Cu and iron oxide nanoparticles played an essential role in the efficient sensing where Fe atoms act as active sites for creatinine oxidation through the secondary amine nitrogen, and Cu nanoparticles acted as an excellent electron-transfer mediator through rGO. The rapid sensor fabrication procedure, mA/cm2 peak current density, a wide range of detection limits, low contact resistance including high selectivity, excellent linear response (R2 = 0.991), and reusability ensured the application of advanced electrochemical sensor toward the POC creatinine detection.