biostudies-literatureHa NSU.S. Department of EnergyNational Institutes of HealthNIGMS NIH HHS3361-3369https://www.ebi.ac.uk/biostudies/studies/S-EPMC10484474biostudies-literatureUnknown23(15)Mass spectrometry (MS) enables detection of different chemical species with a very high specificity; however, it can be limited by its throughput. Integrating MS with microfluidics has a tremendous potential to improve throughput and accelerate biochemical research. In this work, we introduce Drop-NIMS, a combination of a passive droplet loading microfluidic device and a matrix-free MS laser desorption ionization technique called nanostructure-initiator mass spectrometry (NIMS). This platform combines different droplets at random to generate a combinatorial library of enzymatic reactions that are deposited directly on the NIMS surface without requiring additional sample handling. The enzyme reaction products are then detected with MS. Drop-NIMS was used to rapidly screen enzymatic reactionLab on a chipA combinatorial droplet microfluidic device integrated with mass spectrometry for enzyme screening.PMC10484474DE-AC02-05CH11231T32 GM008349NIH 5 T32 GM008349DE-FC0207ER64494Adams PDKuch NBowen BPDeng KSong FKim PWKutschke MParker AHa NSNorthen TRde Raad MAndeer POnley JRGupta KFox BfalseA combinatorial droplet microfluidic device integrated with mass spectrometry for enzyme screening.Mass spectrometry (MS) enables detection of different chemical species with a very high specificity; however, it can be limited by its throughput. Integrating MS with microfluidics has a tremendous potential to improve throughput and accelerate biochemical research. In this work, we introduce Drop-NIMS, a combination of a passive droplet loading microfluidic device and a matrix-free MS laser desorption ionization technique called nanostructure-initiator mass spectrometry (NIMS). This platform combines different droplets at random to generate a combinatorial library of enzymatic reactions that are deposited directly on the NIMS surface without requiring additional sample handling. The enzyme reaction products are then detected with MS. Drop-NIMS was used to rapidly screen enzymatic reaction2023-01-01T00:00:00Z2023 Jul2025-06-01T01:16:41.907Z2025-06-01T01:16:41.907ZS-EPMC104844743740191510.1039/d2lc00980c