An Inexpensive, Point‐of‐Care Urine Test for Bladder Cancer in Patients Undergoing Hematuria Evaluation

Although hematuria (blood in urine) is the most common symptom of bladder cancer, 70–98% of hematuria cases are benign. These hematuria patients unnecessarily undergo costly, invasive, and expensive evaluation for bladder cancer. Therefore, there remains a need for noninvasive office‐based tests that can rapidly and reliably rule out bladder cancer in patients undergoing hematuria evaluation. Herein, a clinical assay for matrix metalloproteinases (“Ammps”) is presented, which generates a visual signal based on the collagenase activity (in urine of patients) on the Ammps substrates. Ammps substrates are generated by crosslinking gelatin with Fe(II) chelated alginate nanoparticles, which precipitate in urine samples. The cleavage of gelatin‐conjugated alginate (Fe(II)) nanoparticles by collagenases generates free‐floating alginate (Fe(II)) nanoparticles that participate in Fenton's reaction to generate a visual signal. In a pilot study of 88 patients, Ammps had 100% sensitivity, 85% specificity, and a negative predictive value (NPV) of 100% for diagnosing bladder cancer. This high NPV can be useful in ruling out bladder cancer in patients referred for hematuria evaluation. In this work, a novel point‐of‐care urine test for detection of bladder cancer that is low cost (5.5 cents/test), ultrasensitive, provides high negative predictive value (100%, in a pilot study of 88 patients), and aims to improve detection/monitoring for bladder cancer by decreasing costs and possibly reducing the number of necessary invasive procedures (i.e. cystoscopies) is presented for the first time.