Fig. 2: High-throughput lipids synthesis and screening platform.

a A schematic to illustrate the high-throughput synthesis method for the toolbox of lipids (1200). b The combinatorial lipids library consists of three components structure (amine headgroups, aldehyde tails, and isocyanide tails). c A schematic diagram shows the lipid nanoparticles (LNPs) components for mRNA encapsulating. d Lipid synthesis, LNPs formulation, and luciferase assay are automated by a liquid handling robot. e The data used for the fine-tuning are depicted in a balloon plot, which involved 1200 lipids for Fluc mRNA (mFLuc) delivery and measuring the relative luciferase expression in HeLa cells. f The loss value on the training set and validation set against fine-tuning steps. g The precision matrix computed on the experimental library of 1200 lipids. The mRNA transfection potency (mTP) is divided into six equal percentiles, which are predicted and compared to the actual results. h Uniform Manifold Approximation and Projection (UMAP) plot of the experimental library, colored by the mTP. Panels (c, d) were created with BioRender.com and released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license.