Physics / mechanism
Liquid biopsy detects circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), exosomes, or cell-free RNA in peripheral blood, urine, or CSF — avoiding surgical tissue access. ctDNA fragments (~160 bp) are isolated via ultracentrifugation or size-exclusion, then sequenced (ddPCR, NGS, or methylation arrays). Key parameters: variant allele frequency (VAF) sensitivity floor ~0.01–0.1% for leading platforms; turnaround 3–7 days; specificity varies with tumour shedding rate. State of the art: Foundation Medicine’s FoundationOne Liquid CDx, Guardant360, and GRAIL’s Galleri (multi-cancer early detection via methylation signatures, ~50 cancer types, sensitivity 67% at >1.4% specificity).
Competitive landscape
Tissue biopsy remains gold standard — higher tumour DNA yield, spatial heterogeneity data, direct histology. Competing molecular approaches: imaging (PET/CT, MRI) for structural detection; proteomics-based serum markers (PSA, CA-125) — cheaper but lower specificity. Within liquid biopsy, ddPCR competes on sensitivity for known variants; NGS panels compete on breadth. Emerging: single-molecule sequencing (PacBio, ONT) for long-read methylation phasing. GRAIL vs. Exact Sciences (Oncotype) vs. Guardant is the core commercial contest.
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Frontier (open questions)
- To be added.