Using Single – Cell Biophysical Properties to Predict Critical Quality Attributes for Cell and Gene Therapy

The ability to monitor Critical Quality Attributes (CQAs) in real-time during the culture has the potential to enhance production efficiency and consistency, shorten the product development cycle and accelerate the time to market. In cell and gene therapy manufacturing, cell state variations during production are closely linked to product quality and yield, but existing sensors lacks the sensitivity to rapidly capture cell state transitions.To address this, we have developed a novel single-cell measurement platform that simultaneously measures biomass and density from the same cell with unprecedented precision. These two biophysical measurements reveal fundamental properties of the cell:biomass corresponds to cell growth and progression through the cell cycle, while density reveals the extent of molecular crowding within the cell which is a proxy for overall fitness.In this talk, I will show how these two biophysical properties predict AAV titer from HEK293cells and reveal functional characteristics of T cells that vary across donors.