Large-batch evaluation of cell counter instrument-to-instrument consistency for cell therapy applications

Abstract

Abstract Cell therapy has been hailed as a medical revolution, and its rise has only increased the importance of accuracy and precision in cell counting. Ensuring the identity, purity, and viability of cell therapy products is critical for increasing efficacy and avoiding potential harmful side effects. The burden of sample analysis often rests on fleets of automated cell counters, leading to the need for confidence that multiple cell counters will give similar results. In this work we compare groups of two distinct cell counting instruments. The first type is a well-established single-sample counter (Cellometer K2), similar to those often found in R&D laboratories. The second type of instrument (Cellaca MX) is a high-throughput cell counter that is often more suitable for a manufacturing environment than its single-sample counterparts. We test the consistency of these cell counters using both live cells and fluorescent beads. We use samples of Jurkat cells to simulate immunotherapy products, and prepare the beads in fixed reference samples to allow comparison of multiple instruments over extended periods of time. We use these beads to investigate agreement among 60 Cellometer K2 instruments and 30 Cellaca MX instruments, what we believe is the largest group of cell counting instruments to be involved in a single comparison study. Our work illustrates experimental approaches suitable for the comparison of multiple cell counting methods. We measure consistency among the cell counters, both within groups of similar instruments and between instrument types. This consistency encourages optimism for “future-proof” assays that can survive the transition from R&D to production with minimal adjustment.