A Sensor Solution to the Femtomolar Problem in Bladder Cancer

Bladder cancer is recognized as the most expensive malignancy per patient due to the necessity of persistent, invasive monitoring and biopsy to diagnose or rule out recurrence, the rate of which approaches 40% of cases. Urine analysis as a screening diagnostic is a potential solution, but remains confounded by biomarker dilution within the bladder, which suppresses concentrations into the exceptionally challenging femtomolar range. In this work, we introduce and mathematically analyze a sensor innovation that addresses this problem in bladder cancer diagnostics by bringing a generic sensor array to the source of biomarker efflux within the lower or upper urinary tract─including the urethra, bladder, ureter, and intrarenal region. We analyze the case of urothelial malignancies producing an efflux of biomarkers into the urine and propose that the use of a sensor probe brought into the proximity of the tumor enhances the detection limit substantially. We show that it is possible to amplify the analyte concentration for detection by more than a factor of 50,000 for protein biomarkers with diffusivities in the range of 10^–10 m²/s in urine. The potential extension to 7 different cancer types with 14 cancer biomarkers is also analyzed. This work provides a new sensor solution to the femtomolar problem in biofluid-based analyses that may lead to earlier detection and treatment and substantially lower the cost of recurrent monitoring.