A robotic system for automated chemical synthesis of therapeutic agents

The development of novel compounds for tissue-specific targeting and imaging is often impeded by a lack of lead compounds and the availability of reliable chemistry. Automated chemical synthesis systems provide a potential solution by enabling reliable, repeated access to large compound libraries for screening. Here we report an integrated solid-phase combinatorial chemistry system created using commercial and customized robots. Our goal is to optimize reaction parameters, such as varying temperature, shaking, microwave irradiation, aspirating and dispensing large-sized solid beads, and handling different washing solvents for separation and purification. This automated system accommodates diverse chemical reactions such as peptide synthesis and conventional coupling reactions. To confirm its functionality and reproducibility, 20 nerve-specific contrast agents for biomedical imaging were systematically and repeatedly synthesized and compared to other nerve-targeted agents using molecular fingerprinting and Uniform Manifold Approximation and Projection, which lays the foundation for creating reliable and reproductive chemical libraries in bioimaging and nanomedicine.