Produce more of the "right" cells with less effort
A uniquely powerful combination of improved initial recovery, extremely efficient washing and removal of platelets consistently delivers a more coherent expansion of T central memory cells compared to other methods tested. For CAR-T cell manufacturing, processing via DLD produces ~50% more of the preferred T cell phenotype following expansion in addition to the significant cost improvements in highly skilled and costly work flows.
Unparalleled Cell Recovery
Microfluidic designs have very little dead volume
As a result, with a gentle efficient and predictable process such as DLD, the cells simply do not have anywhere to hide. As a result, the recovery of cells when processed by DLD is very close to 100%. As shown below, fresh blood was processed by a multi-lane device and recovery of essentially all leucocytes resulted.
Reducing variability - unlocking future automation
DLD processing is more reproducible and yields a better outcome
Our experience has demonstrated that DLD processing, unlike Direct Magnet or Ficoll approaches, where some donors may not respond well to T cell expansion, DLD prepared T cells expand in a coherent and standardized way, and do so with significantly less variation, effectively paving the way to process automation. The data below represent samples that were split following apheresis and had T cells enriched and stimulated either by direct magnetic removal, or by use of Ficoll or or DLD prior to magnetic selection and subsequent expansion - core cell processing steps of CAR therapy manufacture. Initial expansion of the non DLD methods initially looks robust at day 8, but the cells produced are not of the desired phenotype, moreover - the variability of these expansions was >50% for both Day 8 and Day 15 in culture. In sharp contrast, the DLD prepared cells, at both Day 8 and Day 15, expand in a robust and coherent manner for all samples. Further, the T cells produced by the DLD process are of the highly sought T central memory phenotype, resulting in over 50% more T central memory cells produced (top figure).
DLD Efficiency - Platelet Removal
Processing via DLD removes 0.5 log more platelets vs. Ficoll in apheresis samples.In parallel samples DLD processed cells show significantly reduced platelets per leucocyte vs. other methods, reducing the amount of "biological noise" (growth factors/cytokines etc.) that are present in samples that are not as effectively cleaned.
DLD Processed Apheresis Sample
Ficoll (2x Wash)