Label-Free, Novel Electrofluidic Capacitor Biosensor for Prostaglandin E2 Detection toward Early and Rapid Urinary Tract Infection Diagnosis

Abstract

Urine Prostaglandin E2 (PGE2) has been identified as an attractive diagnostic and prognostic biomarker for urinary tract infection (UTI). This work demonstrates the use of PGE2 as a biomarker for rapid and label-free testing for UTI. In this work, we have developed a novel electrofluidic capacitor-based biosensor that can used for home-based UTI management with high accuracy in less than 5 min for small volume urine samples (<60 μL). The PGE2 biosensor works on the principle of affinity capture using highly specific monoclonal PGE2 antibody and relies on non-faradaic electrical impedance spectroscopy (EIS) and Mott−Schottky (MS) for quantifying subtle variations in PGE2 levels expressed in human urine (pH 5−8). Dynamic light scattering experiments were performed to characterize surface charge properties and the impact of bulk interferents on the interfacial modulation of electrical properties due to binding and urine pH variations. Binding chemistry between the key elements of the immunosensor stack was validated using attenuated total reflectance-Fourier transform infrared spectroscopy and surface plasmon resonance studies. Linear calibration dose responses were obtained for PGE2 for both EIS and MS. The sensor reliably distinguished between UTI negative and UTI positive cases for both artificial (pH 5−8) and pooled human urine samples. The sensor was not found to cross-react with Prostaglandin D2, a structurally similar interferent, and other abundant urine interferents (urea and creatinine). Human subject studies confirmed the validity of the sensor for robust and accurate UTI diagnosis. This work can be extended to achieve easy, reliable, and rapid home-based UTI management, which can consequently help physicians with timely and appropriate administration of therapy to improve patient outcomes and treatment success.

DigEST: Digital plug‐n‐probe disease Endotyping Sensor Technology

“…UTIs are common infections that affect individuals of all age groups and are associated with frequent episodes of recurrence and relapse, especially in post‐menopausal women. UTIs, though a common cause of mortality worldwide, is often undiagnosed (especially in resource‐challenged settings due to limited access to laboratory culture tests) and when left untreated can result in severe sequelae such as sepsis and even death, as the causative pathogen ascends from the lower urinary tract to the upper urinary tract and ultimately spread into the bloodstream 12,13,43,49,50 . Thus, tracking the progression of the disease, in a time‐critical fashion, is key for treatment success.…”

“…UTIs, though a common cause of mortality worldwide, is often undiagnosed (especially in resource-challenged settings due to limited access to laboratory culture tests) and when left untreated can result in severe sequelae such as sepsis and even death, as the causative pathogen ascends from the lower urinary tract to the upper urinary tract and ultimately spread into the bloodstream. 12,13,43,49,50 Thus, tracking the progression of the disease, in a time-critical fashion, is key for treatment success. To achieve this, we have developed a rapid UTI biosensor that measures inflammatory biomarkers which are expressed in urine in response to the underlying infection, regardless of the type of pathogen (commonly bacteria).…”

Hydroxypropyl β-Cyclodextrin-Functionalized MoO3 Quantum Dots as a Multifunctional Probe for PGE2 Detection, Bioimaging, and Oxidative Stress Management in Inflammatory Diseases

“…PGE2, a naturally occurring lipid biomolecule with a small molecular size, presents challenges in molecular-level detection. However, earlier literature has made significant strides in sensitive and selective detection methods such as conventional chromatography, mass spectrometry (MS), enzyme-linked immunosorbent assay (ELISA), enzyme immunoassay (EIA), advanced single-molecule arrays (Simoa), , and electrochemical sensors. , However, all primarily rely on the use of either biorecognition elements or a costly centralized technique; there is an emerging consensus on the potential benefits of developing alternative approaches for molecular-level detection of PGE2. The integration of nanostructures, such as quantum dots (QDs), presents promising avenues for molecular diagnosis.…”

Inflammatory Stimuli Responsive Non-Faradaic, Ultrasensitive Combinatorial Electrochemical Urine Biosensor

“…There has been a great advancement in the field of POC diagnostic devices for inflammatory and infectious diseases in the current research space for a home-based multiplexed detection of biomarkers. These urine biosensors in their current formats output biomarker concentrations expressed in the urine samples without any information or interpretation of the severity of the disease and the urgency to schedule a doctor visit [ 6 ]. This defeats the very purpose of early detection through home-based diagnostics, as the patients are not trained medical professionals and hence cannot achieve a holistic understanding of their physiology when they are overwhelmed by looking at a bunch of numbers.…”