Abstract The goal of this R21 project is to develop an in vitro salivary gland Sjögren’s syndrome (SS) tissue chip (SSTC) platform based on microbubble array technology using the MRL/lpr mouse model. SS is an autoimmune disease characterized by sialadenitis (lymphocytic infiltration) in the salivary glands resulting in xerostomia (dry mouth). The disease commonly diagnosed in older women suggesting hormones may contribute to the pathogenesis. Estrogen and androgen receptors are expressed in the salivary gland and on the infiltrated lymphocytic cells. The proposed SSTC will be used to investigate the effect of in vitro and in vivo exposure to a mixture of endocrine disrupting chemical (EDCs) on the growth and function of salivary gland tissue mimetics (SGm). RNAseq studies will be performed on salivary glands to identify differentially regulated gene/pathways associated with sialadenitis and to discover if oral EDC exposure contributes to disease pathogenesis. This project will develop the first ever SSTC that can be used for mechanistic studies and future high throughput drug discovery studies. Currently there are no disease modifying drugs to treat SS patients.