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medRxivGenetic & Genomic MedicinePreprint

Plasma cfDNA analysis can be facilitated by membrane based filtration of whole blood regardless of additive

Amanda N. MarraiD, Dirk van den Boom, Mathias EhrichiD, Christopher K. Ellison

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Abstract

Cell-free DNA (cfDNA) has emerged as a pivotal biomarker for various noninvasive screening applications such as noninvasive prenatal screening, minimum residual disease monitoring, and transplant rejection prediction. However, the efficacy of these applications is heavily reliant on the detection of minority nucleic acid species amidst a vast background of host DNA. Therefore, it is crucial to prevent the dilution of the desired cfDNA signal with genomic DNA originating from white blood cell (WBC) degradation. The most commonly adopted sample collection methods prevent WBC lysis by either adding a stabilizing agent to the collection tube, like Streck, or through immediate centrifugation following the collection of whole blood. In this study, we propose an alternative for plasma sample collection that involves membrane based filtration of plasma from cellular blood components at the point of collection. Our findings demonstrate that cfDNA recovered using this method performs equally or better compared to conventional methods and enables the implementation of novel and more accessible blood collection procedures.

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