Biospecimen Science of Blood for cfDNA Genetic Analyses

Purpose of Review: cfDNA is increasingly used for biomonitoring oncological diseases or pregnancy status by different genetic analyses. Uncontrolled pre-analytical variability impacts the quality and quantity and subsequently undermines the utility of this analyte. In this review, we summarize critical pre-analytical factors to be addressed, to avoid irreproducible results. Recent Findings: cfDNA quantity and quality can be impacted by the in vivo condition of the donor and the ex vivo biospecimen handling prior to the downstream analysis. In vivo, physical and psychosocial stress, circadian rhythmicity, and age appear to be critical. Ex vivo, the blood collection tubes, pre-centrifugation storage temperature and time, and cfDNA extraction kits are important. Summary: To address these critical pre-analytical viabilities, in-process quality control material should be applied. Plasma is preferred to serum, as are blood collection tubes with stabilizers. Finally, the donor status and sample processing should be standardized and documented.