A Proteoform-Resolved Lateral Flow Immunoassay with Antibody Mimics and Engineered Release for Precise Prostate Cancer Diagnosis

Prostate cancer (PCa) is a leading cancer in men, with approximately one in eight diagnosed during their lifetime. Early detection through lateral flow immunoassays (LFIAs) is critical for improving survival rates globally. However, the widely used prostate-specific antigen (PSA) biomarker suffers from limited specificity, as elevated PSA levels are also observed in non-cancerous conditions such as benign prostatic hyperplasia. Recent studies indicate that distinct PSA proteoforms, protein variants resulting from different glycosylation modifications, are linked to specific prostate diseases. Despite this, PSA proteoform-based diagnostics remain underdeveloped due to an incomplete understanding of PSA at the proteome level and detection challenges in false positive and negative. PRIME aims to overcome these barriers by enabling accurate identification of PSA proteoforms without the use of harsh chemicals that could degrade glycosylation patterns. It also seeks to develop a proteoform-resolved LFIA for reliable, ease-to-use and point-of-care PCa diagnosis by integrating antibody mimics and a time-delayed pad into the LFIA platform. The success of PRIME is supported by my expertise in antibody mimic nanoparticle design and mass spectrometry-based proteomics, the world-leading biosensing and LFIA expertise of my host group led by Prof. Dame Molly Stevens at the University of Oxford, and clinical collaboration with Prof. Freddie Hamdy CBE, who provides access to blood samples from the largest randomized controlled study of PCa in the United Kingdom.