Hardware-Attentive Programmable Fourier Ptychography Enables Task-Adaptive Label-Free Virtual Staining.

Virtual staining will enable fast and reagent-free histological imaging toward accurate and consistent pathology diagnosis. However, most current developments rely on heuristic optical landmarks and blind reconstruction, which reduces interpretability, limits cross-task adaptations, and prevents their ultimate clinical translations. Here, we introduce an interpretable Plain-to-Stain framework, "Task-Adaptive Programmable Optics (TAPO)" that removes manual landmark selection by directly tying programmable optical control to task-specific diagnostic objectives. The approach operates under specially modulated visible light, and the highly programmable imaging system decomposes each optical step to execute optics-attention-based reconstruction, leading to task-adaptive multimodal optical encoding for virtual staining. We demonstrated that TAPO successfully passed rigorous validation across diverse tissue types (liver, lung), pathological states (normal, malignant), staining protocols (H&E, Masson's trichrome), magnifications (10×, 20×), and section-thickness settings including routine 4 µm sections and moderately thicker 10 µm sections. Blinded assessments by a panel of board-certified pathologists on multiple virtual slides showed that TAPO results had high clinical acceptance, especially in resolution, cytoplasmic clarity, and nuclear staining, and demonstrated considerable potential for clinical pathology practice.