Introduction and objective
In this work, we have developed a novel label-free and non-culture based, rapid point-of-care testing device for reliable UTI and recurrent UTI diagnosis and management, by combinatorially evaluating critical inflammatory biomarkers i.e., bacterial lipopolysaccharide (LPS), Prostaglandin E2 (PGE2) and Interleukin-8 (IL-8), within 5 minutes, using a drop (<0.2mL) of neat, unprocessed human urine requiring little to no sample preparation at the user end. Our POC diagnostic device can detect pathogen (e.g., bacterial lipopolysaccharide (LPS) and local inflammation (PGE2 and IL-8) and can thus diagnose UTI with high accuracy and precision. This technology is also able to assess risk of rUTI relapse.
Methods
The device platform is label-free and is made of gold-based electrodes immobilized with highly specific capture probes for highly selective detection. A wide dynamic range of 500-5,000pg/mL for PGE2, 1-1000 pg/mL for IL-8 and 1-1500 pg/mL for LPS was achieved using non-faradaic electrochemical impedance spectroscopy. Further, spike-in and recovery studies were performed to test for the accuracy of biomarker quantification. Cross-reactivity studies using potential intereferents were performed to gauge sensor specificity. The sensor performance and the ability to diagnose UTI was validated using human subject studies.
Results
USENSE platform is novel because it can detect UTI relevant biomarkers within a single sensor. This technology addressed the gap in the current urine dipsticks which are semi quantitative or give out a yes/no result. The measurement of two inflammatory markers (IL-8 and PGE2) and one bacterial marker (LPS) allows for a culture-free method with a rapid turnaround time for diagnosis, suitable for routine home-based screening. In addition, the USENSE framework will produce risk scores to help clinicians differentiate between UTI and asymptomatic bacteriuria. Further, USENSE uses PGE2 concentration to predict UTI recurrence and relapse.
Conclusions
This work introduces a novel rapid POC testing device for reliable UTI diagnosis, by combinatorially evaluating critical inflammatory biomarkers using a drop of urine. The device is highly sensitive and specific and shows wide dynamic range, high accuracy, and reliability comparable to established lab standard technique. USENSE can be used as a vital clinical resource to make informed clinical decisions in <5 minutes. This will enable timely and appropriate prescription of antibiotics by allowing early UTI treatment.
Source of funding
Welch Foundation (Grant AT-2030-20200401)
