BioTech IP Review

A liquid biopsy analyzes circulating biomarkers from a non-invasive sample (usually blood) to infer disease presence, subtype, or progression. Instead of sampling tissue directly, it samples what disease sheds into circulation.

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1. Circulating tumor DNA (ctDNA)

• Fragmented DNA released by dying cells
• Contains tumor-specific mutations
• Powerful but sparse in early disease

2. cfDNA methylation patterns

• Tissue-of-origin signatures
• Often more informative than mutations
• Key for early detection

3. Circulating RNA

• mRNA, miRNA, exosomal RNA
• Reflects active biology
• Less stable, but highly informative

4. Proteins & metabolites

• Cytokines, enzymes, metabolic signatures
• Add functional context
• Often non-specific alone

5. Extracellular vesicles (exosomes)

• Carry DNA, RNA, proteins
• Enriched disease signals
• Complex to isolate

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Platform architecture

1. Ultra-sensitive assay
   • Error-corrected sequencing
   • Fragmentomics
   • Deep coverage
2. Multi-analyte integration
   • DNA + methylation + protein
   • Compensates for sparse ctDNA
3. Machine-learning interpretation
   • Pattern recognition
   • Cancer vs non-cancer discrimination
   • Tissue-of-origin prediction
4. Clinical validation at scale
   • Longitudinal cohorts
   • Population studies

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Representative platform strategies

Strategy	Strength	Weakness
Mutation-based	Specific	Low sensitivity early
Methylation-based	Tissue-of-origin	Complex analysis
Multi-omic	High accuracy	Cost & complexity
Fragmentomics	Physics-based signal	Emerging validation

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Liquid biopsy is not a test—it is a platform problem where sensitivity, specificity, and interpretation must scale together.