Colorimetric Detection of Creatinine Based on Plasmonic Nanoparticles via Synergistic Coordination Chemistry.

A simple and portable colorimetric assay for creatinine detection is fabricated based on the synergistic coordination of creatinine and uric acid with Hg(2+) on the surface of gold nanoparticles, which exhibits good selectivity and sensitivity. Point-of-care clinical creatinine monitoring can be supported for monitoring renal function and diagnosing corresponding renal diseases at home.

Development of a point-of-care colorimetric metabolomic sensor platform.

Metabolomics is the large-scale study of small molecule metabolites within a biological system. It has applications in measuring dietary intake, predicting heart disease risk, and diagnosing cancer. Metabolites are often measured using high-end analytical tools such as mass spectrometers or large spectrophotometers. However, due to their size, cost, and need for skilled operators, using such equipment at the bedside is not practical. To address this issue, we have developed a low-cost, portable, optical color sensor platform for metabolite detection. This platform includes LEDs, sensors, microcontrollers, a power source, and a Bluetooth chip enclosed within a 3D-printed light-tight case. We evaluated the color sensor's performance using both a range of dyed water samples as well as well-established colorimetric reactions for specific metabolite detection. The sensor accurately measured creatinine, L-carnitine, ascorbate, and succinate well within normal human urine levels with accuracy and sensitivity equal to or better than a standard laboratory spectrophotometer. Our color sensor offers a cost-effective, portable alternative for measuring metabolites via colorimetric assays, thereby enabling low-cost, point-of-care metabolite testing.

Colloidal Photonic Crystal-Enhanced Fluorescence of Gold Nanoclusters: A Highly Sensitive Solid-state Fluorescent Probe for Creatinine.

Gold nanoclusters (AuNCs) are an intensely pursued class of fluorophores with excellent biocompatibility, high water solubility, and ease of further conjugation. However, their low quantum yield limits their applications, such as ultra-sensitive chemical or molecular sensing. To address this problem, various strategies have been adopted for augmenting their fluorescence intensity. Herein, we report a facile and scalable approach for the fluorescence enhancement of bovine serum albumin (BSA) capped AuNCs (BSA-AuNCs) using periodic, close-packed polystyrene colloidal photonic crystals (CPCs). The slow photon effect at the bandgap edges is utilized for the increased light-matter interactions and thereby enhancing the fluorescence intensity of the BSA-AuNCs. Compared to the planar polystyrene control sample, the CPC film yielded a 14-fold enhancement in fluorescence intensity. Further, we demonstrated the as-prepared BSA-AuNCs-CPC as a solid-state platform for the highly sensitive and selective fluorescence turn-off detection of creatinine at nanomolar level.

Al3+-Responsive Ratiometric Fluorescent Sensor for Creatinine Detection: Thioflavin-T and Sulfated-ß-Cyclodextrin Synergy.

Kidney disorders are a rising global health issue, necessitating early diagnosis for effective treatment. Creatinine, a metabolic waste product from muscles, serves as an ideal biomarker for kidney damage. The existing optical methods for creatinine detection often involve labor-intensive synthesis processes and present challenges with the aqueous solubility and sensitivity to experimental variations. In this study, we introduce a straightforward fluorescence "turn-on" ratiometric sensor system for creatinine detection in aqueous media with a limit of detection of 0.5 µM. The sensor is based on sulfated-ß-cyclodextrin (SCD)-templated H-aggregate of a commercially available, ultrafast rotor dye thioflavin-T (ThT). The Al3+ ion-induced dissociation of ThT-SCD aggregates, followed by reassociation upon creatinine addition, generates a detectable signal. The modulation of monomer/aggregate equilibrium due to the disassembly/reassembly of the ThT-SCD system under Al3+/creatinine influence serves as the optimal strategy for ratiometric creatinine detection in aqueous media. Our sensor framework offers several advantages: utilization of the readily available dye ThT, which eliminates the need for a laborious synthesis of custom fluorescent probes; ratiometric sensing, which improves quantitative analysis accuracy; and compatibility with complex aqueous media. The sensor's practical utility has been successfully demonstrated in artificial urine samples. In summary, our sensor system represents a significant advancement in the rapid, selective, and sensitive detection of the clinically crucial bioanalyte creatinine, offering potential benefits for the early diagnosis and management of kidney disorders.

A graphene nanoplatelet-polydopamine molecularly imprinted biosensor for Ultratrace creatinine detection.

Accurate and reliable analysis of creatinine is clinically important for the early detection and monitoring of patients with kidney disease. We report a novel graphene nanoplatelet (GNP)/polydopamine (PDA)-molecularly imprinted polymer (MIP) biosensor for the ultra-trace detection of creatinine in a range of body fluids. Dopamine hydrochloride (DA) monomers were polymerized using a simple one-pot method to form a thin PDA-MIP layer on the surface of GNP with high density of creatinine recognition sites. This novel surface-MIP strategy resulted in a record low limit-of-detection (LOD) of 2 × 10-2 pg/ml with a wide dynamic detection range between 1 × 10-1-1 × 109 pg/ml. The practical application of this GNP/PDA-MIP biosensor has been tested by measuring creatinine in human serum, urine, and peritoneal dialysis (PD) fluids. The average recovery rate was 93.7-109.2% with relative standard deviation (RSD) below 4.1% compared to measurements made using standard clinical laboratory methods. Our GNP/PDA-MIP biosensor holds high promise for further development as a rapid, accurate, point-of-care diagnostic platform for detecting and monitoring patients with kidney disease.

Development of ratiometric electrochemical molecular switches to assay endogenous formaldehyde in live cells, whole blood and creatinine in saliva.

Formaldehyde is a reactive carbonyl species (RCS) that is produced naturally in the human body via metabolic and epigenetic biochemical processes, yet in high concentrations is highly toxic to the environment as well as to living organisms. Therefore, we designed two ratiometric electrochemical molecular redox probes, Formaldehyde oxidative latent probe (FOLP) and dihydroxy-formaldehyde oxidative latent probe (HFOLP), for the selective profiling of endogenous formaldehyde. FOLP and HFOLP each underwent the aza-Cope reaction with formaldehyde followed by hydrolysis to eliminate unmask redox reporter N-alkylated aminoferrocene (AAF) to monitor their response current. The FOLP and HFOLP sensors showed broad dynamic ranges of 0.12-1000 µM and 0.09-3 mM for formaldehyde with detection limits of 48.2 nM and 31.6 µM, respectively. Also, since formaldehyde is the byproduct of biochemical reactions for detecting creatinine and creatinine is an important biomarker for chronic kidney disease (CKD), we tested the FOLP probe for its ability to monitor creatinine. It successfully did so, and this ability was used to develop an electrochemical platform for the quantification of creatinine; it showed a dynamic range of 3.25-200 µM and a limit of detection (1.3 µM). In addition, the FOLP-based assay platform delivered a reliable analytical performance for the quantification of formaldehyde in human whole blood and of creatinine in saliva, and also for the real-time monitoring of endogenous formaldehyde secretion in HeLa cells. Moreover, the concentrations determined using our method were found to be consistent with those determined using formaldehyde and creatinine fluorometric assay kits.

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.