Digitizing Chemistry Using the Chemical Processing Unit: From Synthesis to Discovery.

Abstract

The digitization of chemistry is not simply about using machine learning or artificial intelligence systems to process chemical data, or about the development of ever more capable automation hardware; instead, it is the creation of a hard link between an abstracted process ontology of chemistry and bespoke hardware for performing reactions or exploring reactivity. Chemical digitization is therefore about the unambiguous development of an architecture, a chemical state machine, that uses this ontology to connect precise instruction sets to hardware that performs chemical transformations. This approach enables a universal standard for describing chemistry procedures via a chemical programming language and facilitates unambiguous dissemination of these procedures. We predict that this standard will revolutionize the ability of chemists to collaborate, increase reproducibility and safety, as we all as optimize for cost and efficiency. Most importantly, the digitization of chemistry will dramatically reduce the labor needed to make new compounds and broaden accessible chemical space. In recent years, the developments of automation in chemistry have gone beyond flow chemistry alone, with many bespoke workflows being developed not only for automating chemical synthesis but also for materials, nanomaterials, and formulation production. Indeed, the leap from fixed-configuration synthesis machines like peptide, nucleic acid, or dedicated cross-coupling engines is important for developing a truly universal approach to "dial-a-molecule". In this case, a key conceptual leap is the use of a batch system that can encode the chemical reagents, solvent, and products as packets which can be moved around the system, and a graph-based approach for the description of hardware modules that allows the compilation of chemical code that runs on, in principle, any hardware. Further, the integration of sensor systems for monitoring and controlling the state of the chemical synthesis machine, as well as high resolution spectroscopic tools, is vital if these systems are to facilitate closed-loop autonomous experiments. Systems that not only make molecules and materials, but also optimize their function, and use algorithms to assist with the development of new synthetic pathways and process optimization are also possible. Here, we discuss how the digitization of chemistry is happening, building on the plethora of technological developments in hardware and software. Importantly, digital-chemical robot systems need to integrate feedback from simple sensors, e.g., conductivity or temperature, as well as online analytics in order to navigate process space autonomously. This will open the door to accessing known molecules (synthesis), exploring whether known compounds/reactions are possible under new conditions (optimization), and searching chemical space for unknown and unexpected new molecules, reactions, and modes of reactivity (discovery). We will also discuss the role of chemical knowledge and how this can be used to challenge bias, as well as define and expand synthetically accessible chemical space using programmable robotic chemical state machines.