Plugging a gap in screening-Arrays of nanoliter-sized plugs of different compositions can be preformed in a three-phase liquid/liquid/gas flow. The arrays can be transported into a microfluidic channel to test against a target (see schematic representation), as demonstrated in protein crystallization and an enzymatic assay.Keywords crystal growth; enzymatic arrays; microreactors; screening methods; three-phase system Herein, we describe a simple, economical microfluidic method of screening a small volume (down to submicroliter volumes) of a solution against a large number of reagents on the nanoliter scale. The use of microfluidics to miniaturize chemical and biological screening is an important and active area of research in such diverse areas as biochemical assays, protein crystallization, and combinatorial chemistry. [1][2][3][4][5][6][7] Nanoliter aqueous plugs (droplets) transported through microchannels in an immiscible liquid have been used in a liquid/liquid flow system and allow miniaturization while eliminating dispersion, [8,9] accelerating mixing, [10] and providing control over the surface chemistry. [11] Applications of such systems to protein crystallization, [3,12] kinetic measurements, [10] assays, [13,14] DNA analysis, [8] and chemical synthesis [15] have been demonstrated. Such plug-based microfluidic systems have been especially attractive for applications in which the concentrations of several reagents had to be varied. The concentrations were varied by rapidly changing the flow rates of the reagent streams as the droplets were formed. [3,12] Plugbased methods of that type require equipment for varying flow rates, and even though such equipment could be as simple as a few computer-controlled syringe pumps, this requirement presents a barrier to many potential users in chemical and biochemical laboratories. In addition, to increase the number of reagents that can be screened, both the number of the microfluidic channels in the device and the number of flow control devices have to be increased proportionally. Herein, we implement a complementary approach that uses pre-formed arrays of plugs to simplify the experiment for the user, relies on a liquid/liquid/gas three-phase flow system to ensure robustness, and allows a much larger number of reagents to be tested in a scalable fashion.