Molecular Recognition to Macroscopic Strain Transduction: A Novel Cross‐Scale Interfacial Sensing Strategy for Point‐of‐Care Prostate Cancer Surveillance

ABSTRACT The urinary sarcosine (Sar) advances prostate cancer (PCa) management, yet its clinical translation for point‐of‐care (POC) use encounters a complex urine matrix with strong interferents for most reported sensors. In response, a novel hydrogel sensor with a cross‐scale interfacial strain sensing strategy is developed for POC testing of urinary Sar in PCa diagnosis. To dynamically preserve “conformational memory” of molecularly imprinted hydrogels under hydration, we establish a quantitative structure‐activity relationship between swelling response and imprinting efficiency to regulate their high‐affinity for specific Sar recognition. Through interfacial coupling design, we achieve strong adhesion between the hydrogel and strain gauge across wet‐dry and soft‐rigid boundaries, enabling the translation of molecular‐scale Sar recognition events into measurable macroscopic strain signals with minimal signal attenuation and energy dissipation. To maximize signal transduction efficiency, the complex 3D and anisotropic swelling of the hydrogel is engineered to match the planar 2D response of the strain gauge, thereby enhancing overall strain‐to‐signal sensitivity and detection limit. Consequently, the developed sensor exhibits competitive analytical performance compared to existing technologies, notably in a wide detection range (10 −3 to 10 6 µ M ) with a rapid response (2 min). Our developed hydrogel‐based sensor offers a promising POC strategy for urinary Sar detection, advancing diagnostics in PCa care.