Label Free, Lateral Flow Prostaglandin E2 Electrochemical Immunosensor for Urinary Tract Infection Diagnosis

Abstract

A label-free, rapid, and easy-to-use lateral flow electrochemical biosensor was developed for urinary tract infection (UTI) diagnosis in resource challenged areas. The sensor operates in non-faradaic mode and utilizes Electrochemical Impedance Spectroscopy for quantification of Prostaglandin E2, a diagnostic and prognostic urinary biomarker for UTI and recurrent UTI. To achieve high sensitivity in low microliter volumes of neat, unprocessed urine, nanoconfinement of assay biomolecules was achieved by developing a three-electrode planar gold microelectrode system on top of a lateral flow nanoporous membrane. The sensor is capable of giving readouts within 5 min and has a wide dynamic range of 100–4000 pg/mL for urinary PGE2. The sensor is capable of discriminating between low and high levels of PGE2 and hence is capable of threshold classification of urine samples as UTI positive and UTI negative. The sensor through its immunological response (directly related to host immune response) is superior to the commercially available point-of-care UTI dipsticks which are qualitative, have poor specificity for UTI, and have high false-positive rates. The developed sensor shows promise for rapid, easy and cost-effective UTI diagnosis for both clinical and home-based settings. More accurate point-of-care UTI diagnosis will improve patient outcomes and allow for timely and appropriate prescription of antibiotics which can subsequently increase treatment success rates and reduce costs.

Advances in electrochemical sensors based on nanomaterials for the detection of lipid hormone

“…In previous reports, electrochemical sensors of prostaglandin E1 (Zheng et al, 2016) and 8-iso-prostaglandin F2α (Sanchez-Tirado et al, 2017) have been successively reported. With the deepening understanding of the fatty acid derivative hormone and the development of electrochemical sensors, Ganguly et al (2021) developed a three-electrode planar gold microelectrode system with flow-based nanopore membranes for electrochemical immunosensors for detecting prostaglandin E2 (PGE2). This sensor can be used in both clinical and home settings for a more immediate, fast and accurate diagnosis of urinary tract infection.…”

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

“…For quantifying inflammation, urine has been widely studied in the research space, mainly because it is easily accessible, is “quiescent” since the molecular activity does not change much after sampling and does not require specialized sampling by trained professionals, and hence can be easily deployed for home-based routine screening [ 1 , 5 ]. 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.…”

“…The transduction of the antibody-antigen binding event is achieved by monitoring the interfacial modulation of the electrode-urine interface as a function of the binding. The sensor is in the form of a standard planar gold three-electrode electrochemical system on a flexible, nanoporous lateral flow membrane substrate [ 5 , 13 ]. The porosity of the substrate allows for a wide dynamic range and enhanced sensitivity due to the phenomena and macromolecular crowding which is especially important for developing ultrasensitive sensors for detecting cytokines that are expressed in very low concentrations in biofluids [ 4 , 14 , 15 ].…”

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

“…24,25 Thus, PGE2 was chosen as the target biomarker to achieve early, accurate single number quantitative readouts, independent of the causative pathogen. 26 To produce a costeffective, portable, rapid diagnostic device, electrochemical/ electroanalytical methods were chosen as the transduction mechanism for biosensing. Electrochemical biosensors are popular for building POC devices as they are (i) small, portable, mass-producible, and inexpensive as they are compatible with microfabrication and (ii) are reliable as they seamlessly integrate with miniaturized electronics with high fidelity and are generally programmed to give out quantitative results.…”

“…In their recent work, Ebrahimzadeh et al showed that urinary Prostaglandin E2 (PGE2) is one such biomarker that can serve not only as a reliable diagnostic but also a prognostic biomarker for rUTI in postmenopausal women . PGE2, which is an enzymatic product of cyclooxygenase-2 (COX-2), is a critical mediator of the inflammatory response. , Thus, PGE2 was chosen as the target biomarker to achieve early, accurate single number quantitative readouts, independent of the causative pathogen . To produce a cost-effective, portable, rapid diagnostic device, electrochemical/electroanalytical methods were chosen as the transduction mechanism for biosensing.…”