Screening of huge and numerous libraries is the ‘bread and butter’ within the first part of the invention of novel medicine. Nevertheless, upkeep and periodic renewal of high-quality giant compound collections pose a substantial logistic, environmental and financial downside. Right here, we train another, the ‘on-the-fly’ synthesis of huge and numerous libraries on a nanoscale in a extremely automated style. For the primary time, we present the feasability of the synthesis of a big library based mostly on 16 completely different chemistries in parallel on a number of 384-well plates utilizing the acoustic allotting ejection (ADE) know-how platform. In distinction to combinatorial chemistry, we produced 16 scaffolds on the similar time and in a sparse matrix style, every compound by a random mixture of a big constructing block range. Synthesis, analytics, resynthesis of chosen compounds, and chemoinformatic evaluation of the library is described. Benefits of the herein described automated nanoscale synthesis strategy embrace nice library range, absence of library storage logistic, supperior economics, pace of synthesis by automation, elevated security, therefore sustainable chemistry.