FluoCLIP: Stain-Aware Focus Quality Assessment in Fluorescence Microscopy

Accurate focus quality assessment (FQA) in fluorescence microscopy remains challenging, as the stain-dependent optical properties of fluorescent dyes cause abrupt and heterogeneous focus shifts. However, existing datasets and models overlook this variability, treating focus quality as a stain-agnostic problem. In this work, we formulate the task of stain-aware FQA, emphasizing that focus behavior in fluorescence microscopy must be modeled as a function of staining characteristics. Through quantitative analysis of existing datasets (FocusPath, BBBC006) and our newly curated FluoMix, we demonstrate that focus-rank relationships vary substantially across stains, underscoring the need for stain-aware modeling in fluorescence microscopy. To support this new formulation, we propose FluoMix, the first dataset for stain-aware FQA that encompasses multiple tissues, fluorescent stains, and focus variations. Building on this dataset, we propose FluoCLIP, a two-stage vision-language framework that leverages CLIP's alignment capability to interpret focus quality in the context of biological staining. In the stain-grounding phase, FluoCLIP learns general stain representations by aligning textual stain tokens with visual features, while in the stain-guided ranking phase, it optimizes stain-specific rank prompts for ordinal focus prediction. Together, our formulation, dataset, and framework establish the first foundation for stain-aware FQA, and FluoCLIP achieves strong generalization across diverse fluorescence microscopy conditions.