Development of Bladder Cancer Diagnosis Kit Using Buoyancy-Lifted Orthogonal-Organogel Messenger

Abstract

Early diagnosis of bladder cancer reduces mortality and improves patients' quality of life. Therefore, a POCT device capable of regular and frequent bladder cancer monitoring is essential. Many POCT devices for diagnosing bladder cancer using urine samples have been developed. However, there are limitations due to the inherent characteristics of urine, such as ultra-low biomarker content by kidney filtration, a wide pH range, and interfering molecules such as hematuria and ions. Especially the early stage of bladder cancer, in which the biomarker concentration is much lower than the advanced stages, is difficult to diagnose through a POCT device. Here, I report a urine-based bladder cancer diagnosis kit using buoyancy-lift orthogonal organogel messenger. The system measures biomarkers in the following ways. 1) A buoyant organogel (signal transporter) containing a solvatochromic fluorescent dye is designed to float upwards for signal transduction. 2) Bigel film composed of commercial hydrogel encapsulating buoyancy signal organogel is degraded with bladder cancer enzyme biomarker. 3) Designed with a dodecane/aqueous bilayer (clinical urine sample), the biomarker recognition was isolated in the aqueous layer, and the transduction and amplification of the signal occurred in the organic layer. Through this, early diagnosis is possible without the interference of various biomolecules in the urine sample. This point-of-care device showed high sensitivity and selectivity, identifying up to 0.25 mU/ml enzyme biomarkers in clinical urine samples. In the clinical test, the device discriminated between bladder cancer patients and non-bladder cancer patients with 91.6% accuracy (a group of 47 patients and 15 non-bladder cancer patients). In the samples of early-stage bladder cancer patients, the kits displayed a diagnostic accuracy of 91.4%, unlike the widely used commercial bladder cancer diagnosis kit, NMP22 Bladder Check, which showed 16% accuracy in the same clinical samples.