Abstract: The present disclosure provides systems, methods, and apparatus for preparing biological samples (e.g., plasma) for sequencing (e.g., DNA sequencing, e.g., third generation sequencing). Moreover, the present disclosure provides various systems, methods, and apparatus that employ this sample preparation technology in the identification of biomarkers for detection of a disease or condition. For example, in certain embodiments, the biological sample preparation method includes capturing fragments of cell free DNA (cfDNA) with capture probes, converting the captured DNA fragments into circular DNA, and amplifying the circular DNA by performing rolling circle amplification (RCA). In particular, it is presently found that by performing this sample preparation method, it is possible to more successfully distinguish true alterations (e.g., aberrant methylation status and/or genomic mutations) from technical/sequencing artifacts.