The　integration　of　simple　fabricated　paper　devices　with　a　multiplexing　fluid　control　technology　are　the　keys　for　extending　traditional　microfluidic　applications　to　paper-based　devices.　However,　paper　devices　to　date　have　lacked　a　method　for　addressing　the　integration　of　complex　fluid　manipulations.　By　featuring　a　scalable　and　programmable　mechanical　valve　matrix　that　is　actuated　by　push-pull　solenoids,　we　present　a　paper　microfluidic　multiplexing　technology　for　performing　biochemical　assays　in　a　high　degree　of　autonomy.　The　technology　allows　every　channel　of　a　paper　network　to　be　autonomously　addressed　and　isolated　while　uses　a　minimal　number　of　control　elements,　efficiently　reducing　its　complexity.　The　technology　is　implemented　in　an　integrated　portable　system　including　a　multiplexor　controller,　a　relay　matrix,　a　paper　device,　on-chip　temperature　control　unit　and　an　image　analyzer.　Biochemical　reaction　signals　can　be　acquired　and　automatically　interpreted　via　a　self-built　mobile　App.　A　prototype　that　consists　of　8　independent　valve　lines　was　demonstrated,　allowing　multiplexed　control　of　a　paper　device　with　16　operating　channels.　After　thoroughly　studying　the　behaviour　of　fluid　transport　in　the　paper　device　using　both　numerical　simulation　and　experimentations,　multiplex　colorimetric　assays　of　heavy　metal　samples　and　glucose　in　common　soft　drinks　and　artificial　saliva　samples　were　analyzed.　To　the　best　of　our　knowledge,　this　is　the　first　demonstration　of　a　simple　fabricated　paper　device　integrated　with　a　valve　multiplexing　technology.　The　scalability　of　this　integration　makes　the　technology　ideally　suited　for　high-throughput　analysis　and　holds　great　potential　for　progressing　large　scale　integration　of　paper　microfluidics.　©　2020　Elsevier　B.V.