Student Poster Finalist: A novel, non-culture based electrochemical sensor for multiplexed biomarker quantification towards rapid Urinary Tract Infection management

Urinary Tract Infections (UTIs) are among the most common infections that affect nearly 10.5 million patients per year. Associated with recurrence and relapse, these require frequent medical attention. The current gold standard for UTI detection is clinical urine culture. This method demands specialized equipment, trained professionals and at least 2-3 days to get lab results. Due to these delays, the patients are prescribed a broad spectrum of antibiotics to prevent complications. This often results in antibiotic resistance making treatment complicated, and ineffective, often resulting in relapse and longer hospital stay. We have developed a biosensor that quantifies three UTI relevant inflammatory biomarkers in very low volumes ( < 60μL) of neat, unfiltered urine within 5 minutes. Thus, our sensor conveniently eliminates the need for culturing bacteria and allows to reliably measure the levels of the biomarkers without any sample preparation steps such as urine pre-filtration. The proposed sensor consists of a standard planar three electrode system (Au working and counter, Ag reference electrodes) and relies on a highly specific affinity-based assay-based label free detection (no redox tagging) of the three inflammatory biomarkers viz., Prostaglandin E2 (PGE2), Interleukin-6 (IL-6) and C-Reactive Protein (CRP) in human urine. The assay contains monoclonal antibodies which preferentially capture their target antigens (PGE2, IL-6 and CRP) with high specificity.  The antibodies are anchored to the gold working electrode by using thiol crosslinker, DSP (dithiobis (succinimidyl propionate). Binding of the target analytes to the respective capture probes causes a dose-dependent modulation of the dielectric properties at the Electrical Double Layer (EDL) at the electrode/ human urine interface. Changes in these parameters are transduced by the sensor using frequency specific (100 Hz) Non-Faradaic Electrochemical Impedance Spectroscopy. Highly sensitive and linear calibration dose response plots were obtained, and the proposed electrochemical sensor shows potential of precisely quantifying PGE2, IL-6 and CRP concentrations for wide dynamic ranges of  analyte doses (500-5000 pg/mL for PGE2, 10-500 pg/mL for IL-6 and 10-1000 ng/mL for CRP) over the entire physiological pH range of human urine (pH 5 to 8). Human subject studies confirmed the accuracy and reliability of the response when compared with traditional ELISA assays. This device shows potential as a vital clinical resource which will improve patient outcomes by transforming the UTI clinical workflow and by enabling clinical decision making in less than 5 minutes (unlike the typical 2-3 day turn-around times associated with culture based diagnostic alternatives). This will enable timely and appropriate prescription of antibiotics and steroids and hence reduce the financial and psychological burden of the patients and their families. The proposed sensor can also be rendered as a point-of-care device for home based monitoring of symptoms and tracking treatment efficacy to plan timely visits to the doctor’s clinic.