Rapid Arbitrary‐Shape Microscopy of Unsectioned Tissues for Precise Intraoperative Tumor Margin Assessment

This study presents a novel microscopic imaging system capable of rapid, section‐free scanning of irregular tissue surfaces, delivering high sensitivity for detecting cancer cell clusters during intraoperative tumor margin assessment. Abstract Rapid and accurate intraoperative examination of tumor margins is crucial for precise surgical treatment, yet current methods are limited by incomplete tissue sampling and time‐consuming sample sectioning. The Rapid Arbitrary‐Shape Microscope (RAM) is developed, a bedside imaging system that enables high‐speed, 3D microscopy of irregular tissue surfaces without sectioning, providing cellular‐resolution images within minutes while preserving tissue morphology post‐excision. RAM precisely integrates a 3D scanning module with a robotic platform, seamlessly combining morphological measurements with robotic‐driven pathological microscopy. In studies involving metastatic tumors in 39 mouse liver and spleen samples, RAM demonstrated high accuracy in detecting positive margins containing cancer cells, achieving a sensitivity of 99.1% and a specificity of 82.9%. The system's capability is further validated on 12 skin cancer samples from 10 human subjects using nondestructive imaging, highlighting its potential to reduce surgical time and minimize the risk of overlooking residual cancer at surgical margins during intraoperative evaluation. This study presents a novel microscopic imaging system capable of rapid, section-free scanning of irregular tissue surfaces, delivering high sensitivity for detecting cancer cell clusters during intraoperative tumor margin assessment. Abstract Rapid and accurate intraoperative examination of tumor margins is crucial for precise surgical treatment, yet current methods are limited by incomplete tissue sampling and time-consuming sample sectioning. The Rapid Arbitrary-Shape Microscope (RAM) is developed, a bedside imaging system that enables high-speed, 3D microscopy of irregular tissue surfaces without sectioning, providing cellular-resolution images within minutes while preserving tissue morphology post-excision. RAM precisely integrates a 3D scanning module with a robotic platform, seamlessly combining morphological measurements with robotic-driven pathological microscopy. In studies involving metastatic tumors in 39 mouse liver and spleen samples, RAM demonstrated high accuracy in detecting positive margins containing cancer cells, achieving a sensitivity of 99.1% and a specificity of 82.9%. The system's capability is further validated on 12 skin cancer samples from 10 human subjects using nondestructive imaging, highlighting its potential to reduce surgical time and minimize the risk of overlooking residual cancer at surgical margins during intraoperative evaluation. Advanced Science, EarlyView.