Project Summary Prostate cancer is a leading cause of cancer mortality in medically underserved men, due to limited access to quality health care resources. Longitudinal monitoring of very low blood prostate specific antigen (PSA) concentrations (tens of pg/mL) is an important tool for clinical surveillance of patients post radical prostatectomy or radical radiotherapy. Such monitoring requires high sensitivity diagnostic assays. However, it is challenging for underserved patients suffering from health disparities to get access to the state-of-the-art diagnostic resources. Lacking the appropriate resources and infrastructure results in loss-to-follow-up, increased tumor recurrence and metastasis without surveillance. Residents in Chinatown communities across the US represent such medically underserved populations suffering from health disparities, due to language, cultural and economic barriers. Our goal is to reduce prostate cancer care disparities by providing access to high sensitivity PSA measurement with minimal infrastructure needs, by further developing and validating an ultrasensitive, convenient, low-cost and widely deployable Microbubbling PSA Platform. This platform builds on our innovative Microbubbling Digital Assay technology, capable of quantitating femtomolar concentrations of protein biomarkers in various biological fluids, including blood, using smartphones. We have demonstrated that, using blood samples from prostate cancer patients, the Microbubbling PSA assay has comparable accuracy, but ~200 fold higher sensitivity than central laboratory state-of-the-art. The clinical feasibility and viability of the technology has also been successfully proven for various clinical applications, including bhCG detection and RADx-funded and FDA EUA-submitted SARS-CoV-2 antigen detection. In addition, we have developed and demonstrated feasibility of an automated microfluidics platform that integrates all Microbubbling assay steps. We propose to (Aim 1) integrate the Microbubbling PSA Assay into the automated microfluidics platform suitable for home or urologist office use, without infrastructure or sophisticated instrument needs. This platform only requires a few drops of fingerstick blood as input and a smartphone for high sensitivity quantitative PSA readout in 20 min. (Aim 2) By collaborating with the central clinical laboratory at Hospital of the University of Pennsylvania, we will validate the clinical performance of the Microbubbling PSA Platform by comparing with FDA- approved state-of-the-art, using clinical blood samples. Furthermore, we will collaborate with Dr. Wenwu Jin, a urologist, Chief of Surgery and local expert practicing in Chinese Hospital in San Francisco Chinatown to validate the usability of the platform in medically underserved Chinatown residents.