Clinically constrained optical design of a high-numerical aperture miniature immersion objective for probe-based confocal laser endomicroscopy.

Confocal laser endomicroscopy (CLE) is a critical modality for the early, minimally invasive diagnosis of intraluminal diseases. However, its clinical translation is constrained by the inherent optical-mechanical trade-offs between numerical aperture (NA), probe diameter, and clinical maneuverability. Achieving high-performance imaging within the strict dimensional limits of standard biopsy channels remains a significant technical bottleneck. To address these challenges, we propose a clinically constrained optical design strategy. This integrated design approach incorporates anatomical boundary constraints directly into the optical optimization process. Based on this method, the developed miniature immersion objective achieved a 0.78 μm lateral resolution across a 300 μm field of view, while the integrated pCLE probe maintained a 1.1 μm lateral resolution. This system realizes stable cellular-level imaging under constrained geometry. It is bending-compatible and clinically deployable. Animal experiments and representative histology-correlated clinical gastric images demonstrated the feasibility of resolving tissue microstructures and clinically relevant mucosal abnormalities, supporting the translational potential of the integrated pCLE probe.