Label-free in-line characterization of immune cell culture using quantitative phase imaging

Cell therapies, such as T cell immunotherapies, hold significant promise for treating complex diseases; however, their widespread adoption has been hindered by challenges related to monitoring cells during culture, which has affected their consistency, potency, and cost. Here, we present a compact, low-cost, label-free quantitative phase imaging (QPI) platform to enable continuous, non-destructive, in-line monitoring of T cell cultures within bioreactors. We further develop quantitative, image-based assays that accurately characterizes T cell culture viability and activation from over 50 independent donors-including therapeutically relevant CAR-T cells - while also preserving culture sterility and eliminating the need for disruptive sampling and endpoint assays. Our findings establish a QPI-pipeline for label-free, in-line cell monitoring and characterization which can significantly improve cell manufacturing processes.