Safety-by-design using forward and inverse multi-target machine learning

The economic and social future of nanotechnology depends on our ability and manufacture nanomaterials that avoid potential toxicity, by identifying them before they are made, used and released into the environment. Safety-by-design is a framework for including these issues at an early stage of the development process, but balancing multiple nanoparticle properties and selection criteria remains challenging. Based on a synthetic data set of over 19,000 possible sunscreen product specifications, we have used multi-target machine learning to predict the corresponding size, shape, concentration and polytype of titania nanoparticle additives. The study considers the optical properties responsible for the sun protection factor and product transparency, including the extinction coefficients for ultra violet and visible light, and the potential for toxicity due to the generation of reactive oxygen species from the photocatalytically active facets of both anatase and rutile nanoparticles, as a function of the size and shape. We predict a number of conventional forward structure/property and property/product relationships, but show that a direct structure/product relationship provides superior performance when predicting multiple properties or product specifications simultaneously. These models are then inverted, re-optimized and re-trained to provide focused, high performing inverse design models that do not require additional optimization, and are capable of identifying nanoparticle configurations outside of the training set. The ability to directly predict suitable nanoparticle structures that conform to prerequisite sun protection, transparently and potential toxicity thresholds represents a new approach to safety-by-design that can be applied to other products and materials where multiple design criteria must be met at the same time.