Photonic crystal barcode microfluidic chip for smart screening of lactogenic Chinese herbs using human mammary organoids.

Postpartum insufficient lactation is challenging to maternal and infant health, yet safe and effective lactation-promoting drugs remain lacking. Here, we present an integrated smart screening platform that combines human mammary organoids with a photonic crystal barcode microfluidic chip for high-throughput identification and mechanistic elucidation of lactation-promoting traditional Chinese medicines (TCMs). Human mammary organoids recapitulate key structural and functional features of native mammary tissue and, critically, acquire the capacity to stably secrete milk proteins including TIMP1, which serves as a quantifiable lactogenic marker. The photonic crystal barcodes, fabricated as monodisperse silica colloidal crystal microspheres with tunable structural colors, are functionalized with capture antibodies and embedded in a herringbone-structured microfluidic chip, enabling in situ, visual, and highly sensitive fluorescence-based detection of secreted proteins. Using this system, we screen 18 TCM compounds and identify curcumin, puerarin, and forsythoside H as the three most effective candidates for enhancing TIMP1 secretion in vitro. Notably, in vivo experiments in a postpartum mouse model demonstrated that all three TCMs markedly induced milk yield and mammary alveolar development. RNA-seq analysis further unveils that forsythia uniquely regulates a series of pathways involving reprogramming of carbohydrate metabolism, amplification of estrogen/prolactin hormone signaling cascades, and induction of mammary epithelial differentiation. This synergistic activation of core lactogenic pathways provides a molecular basis for forsythia's superior lactation-promoting efficacy. These findings demonstrate that the present platform shows potential for efficient screening of lactation-promoting herbs and advancing the modernization of TCMs in lactation management.