Zwitterionic Microgel Preservation Platform for Circulating Tumor Cells in Whole Blood Specimen

The immediate processing of whole blood specimen is required in circulating tumor cell-based liquid biopsy. The reliable blood specimen stabilization toward preserving circulating tumor cells can enlarge the geographic sharing regions for precise rare-cell technology; however, it remains a challenge owing to circulating tumor cells fragility and rarity. Herein, we aim to establish a zwitterionic magnetic microgel platform to stabilize the whole blood specimen for long-term hypothermic preservation of model circulating tumor cells. In a cohort study of 20 cancer patients, their blood specimen can be preserved up to 7 days without compromising circulating tumor cell viability and RNA integrity, thereby excessively doubling the viable preservation duration. The 7day microgel-preserved blood specimen is able to reliably detect cancer-specific transcripts, similar to fresh blood specimens; while up/down expression regulation of 1243 genes in model circulating tumor cells preserved by commercial protectant. Mechanistically, the zwitterionic microgel assembly counters the cold-induced excessive reactive oxygen species and platelet activation, as well as extracellular matrix loss-induced cell anoikis, to prevent circulating tumor cell loss in the whole blood specimen. The present work serves as a springboard for the development of blood-based noninvasive diagnostics.