Liquid biopsy & ctDNA diagnostics

01Overview and value chain#

Markers EC: IVDR 2017/746 | OECD: Biotech-health | Regulator: FDA (USA), EMA (European Union), NMPA (China)

Liquid biopsy and ctDNA diagnostics detect and sequence circulating tumor DNA (ctDNA) — tumor-derived DNA fragments shed into the bloodstream — from a blood draw instead of a surgical tissue sample, using next-generation sequencing (NGS) or digital PCR to identify actionable mutations, guide companion-diagnostic drug matching, and track molecular residual disease (MRD) after treatment. Guardant Health’s Guardant360 CDx received FDA approval as a companion diagnostic for Boehringer Ingelheim’s HERNEXEOS in 2026, and the company’s newly expanded Guardant360 Liquid CDx panel is the largest FDA-approved liquid biopsy panel to date, with a 100x expanded genomic footprint. Natera’s Signatera MRD test has IVDR certification across multiple cancers, is FDA-approved as a companion diagnostic in muscle-invasive bladder cancer, and is now recommended by NCCN guidelines for bladder-cancer ctDNA-MRD testing. Foundation Medicine (Roche) has stacked FDA companion-diagnostic approvals for FoundationOne CDx and FoundationOne Liquid CDx across NSCLC, prostate and other indications, and launched FoundationOneMRD, combining structural-variant detection with digital PCR. Sysmex Inostics supplies PlasmaSeqSensei NGS kits and targeted oncology panels, with published clinical evidence that its circulating-tumor-HPV-DNA assay predicts survival. MedGenome contributes ctDNA biomarker research and oncology genomics services from India, and Burning Rock Biotech is a Nasdaq-listed Chinese liquid-biopsy company running NGS-based ctDNA panels for solid-tumor profiling.

The key directions of liquid biopsy and ctDNA diagnostics are:

1. Companion diagnostics (Companion Diagnostics): ctDNA panels approved alongside a specific targeted therapy to select eligible patients — Guardant360 CDx, FoundationOne CDx/Liquid CDx, Signatera CDx.
2. Molecular residual disease monitoring (Minimal Residual Disease MRD): post-treatment blood tests that detect trace ctDNA to flag recurrence before imaging can — Signatera, FoundationOneMRD.
3. Broad genomic profiling (Circulating Tumor DNA): pan-cancer NGS panels sequencing hundreds of genes from a single blood draw for treatment selection — Guardant360, Sysmex Inostics targeted panels.
4. Ultra-sensitive detection chemistry (Digital PCR): digital PCR and tumor-informed sequencing methods pushing detection sensitivity into the parts-per-million range needed for MRD.

Sectoral value chain#

[blood draw & cfDNA/ctDNA extraction] ──> [library prep & NGS / digital PCR] ──> [bioinformatics variant calling]
                                                        │
                                          (companion-diagnostic / MRD algorithm)
                                                        │
                                                        ▼
[longitudinal MRD monitoring] <─── [regulatory approval & reimbursement] <─────┘

Value chain levels#

Cross-cutting technologies of the sector:

• Circulating tumor DNA sequencing (Circulating Tumor DNA): NGS panels sequencing cfDNA to detect tumor-derived mutations at low allele fractions without a surgical biopsy.
• Digital PCR (Digital PCR): partition-based PCR quantification reaching the ultra-low-frequency sensitivity MRD detection requires, complementing broader NGS panels.
• Tumor-informed MRD algorithms (Minimal Residual Disease MRD): patient-specific variant panels (built from the resected tumor) tracked in serial blood draws to detect molecular recurrence months before imaging.

02US#

The US anchors the global liquid-biopsy/ctDNA industry, with Guardant Health, Natera and Foundation Medicine holding the deepest FDA companion-diagnostic and MRD approval portfolios.

Guardant Health, Natera, Foundation Medicine, FDA#

• Guardant Health: Guardant360 CDx is FDA-approved as a companion diagnostic for Boehringer Ingelheim’s HERNEXEOS, and the newly expanded Guardant360 Liquid CDx is the largest FDA-approved liquid biopsy panel to date, with a 100x expanded genomic footprint.
• Natera: Signatera holds EU IVDR certification across multiple cancers, FDA companion-diagnostic approval in muscle-invasive bladder cancer, an NCCN-guideline recommendation for bladder-cancer ctDNA-MRD testing, and a broad clinical launch of the ultra-sensitive Signatera Genome MRD test.
• Foundation Medicine (Roche): FoundationOne CDx and FoundationOne Liquid CDx carry stacked FDA companion-diagnostic approvals (Tepmetko/tepotinib in MET exon-14-skipping NSCLC; Talzenna/talazoparib with Xtandi/enzalutamide in HRR-mutated mCRPC; Akeega/niraparib-abiraterone in BRCA-positive mCRPC), and FoundationOneMRD combines structural-variant detection with digital PCR.
• FDA framework: liquid-biopsy tests enter the US market as PMA-approved companion diagnostics or as laboratory-developed tests (LDTs) under CLIA, with an accelerating cadence of drug-linked CDx approvals since 2024.

03CN#

China hosts a growing liquid-biopsy diagnostics industry led by Nasdaq-listed Burning Rock Biotech, operating under NMPA oversight.

Burning Rock Biotech, NMPA#

• Burning Rock Biotech (燃石医学): a Nasdaq-listed (BNR) Chinese liquid-biopsy oncology company running NGS-based ctDNA panels for solid-tumor genomic profiling, with continuing 2025-2026 clinical and commercial developments reported in Chinese financial media.
• Domestic market: China’s oncology NGS testing market has grown around companion-diagnostic and MRD use cases similar to the US, with local players competing alongside multinational panels under NMPA registration.
• NMPA framework: liquid-biopsy diagnostic kits are registered and controlled as in-vitro diagnostic (IVD) medical devices under NMPA, with companion-diagnostic claims requiring linkage to an approved therapy label.

04EU#

Europe’s liquid-biopsy tier is anchored by Sysmex Inostics, a German NGS/digital-PCR oncology diagnostics specialist operating under the EU’s In Vitro Diagnostic Regulation.

Sysmex Inostics, IVDR#

• Sysmex Inostics (Hamburg, Germany): supplies PlasmaSeqSensei NGS kits and targeted panel assays for oncology, with published clinical evidence (JAMA Oncology) that its circulating-tumor-HPV-DNA (HPV-Seq) assay predicts improved survival when used to monitor treatment clearance.
• IVDR framework: liquid-biopsy and ctDNA assays sold in the EU must meet the In Vitro Diagnostic Regulation (IVDR 2017/746)’s conformity-assessment requirements, a bar Natera’s Signatera has cleared across multiple cancer types, illustrating the compliance path non-EU vendors also follow to sell into Europe.

05Leading companies and research institutes#

06Tech stack and innovations#

The stack pairs cell-free DNA extraction with ultra-sensitive NGS and digital-PCR detection chemistries, then layers tumor-informed bioinformatics to separate true low-frequency tumor signal from background sequencing noise.

1. Broad NGS genomic profiling (Circulating Tumor DNA):
   • Guardant360’s expanded panel and FoundationOne Liquid CDx sequence hundreds of cancer genes directly from plasma cfDNA, matching patients to targeted therapies without a tissue biopsy.
2. Tumor-informed MRD detection (Minimal Residual Disease MRD):
   • Natera’s Signatera and Foundation Medicine’s FoundationOneMRD build a patient-specific variant panel from the resected tumor, then track those exact variants in serial blood draws at sensitivity sufficient to flag recurrence before imaging.
3. Digital PCR and targeted panels (Digital PCR):
   • Sysmex Inostics’ PlasmaSeqSensei kits and targeted panel assays (including circulating-tumor-HPV-DNA) use partition-based digital PCR alongside NGS for ultra-low-frequency variant detection.
4. Companion-diagnostic regulatory linkage (Companion Diagnostics):
   • US CDx approvals (Guardant360 CDx, FoundationOne CDx/Liquid CDx, Signatera CDx) and EU IVDR certification tie the assay directly to an approved drug label, the commercial core of the sector’s reimbursement model.

07Value chains and production pipelines#

Industrial pipeline of a ctDNA liquid-biopsy test (FDA CDx / IVDR 2017/746)#

┌───────────────────────────┐      ┌───────────────────────────┐
│ 1. Blood draw & cfDNA     │ ───> │ 2. Library prep & NGS /   │
│    extraction             │      │    digital PCR             │
└───────────────────────────┘      └───────────────────────────┘
                                                   │
                                                   ▼
┌───────────────────────────┐      ┌───────────────────────────┐
│ 4. Companion-diagnostic / │ <─── │ 3. Bioinformatics &      │
│    MRD report             │      │    variant calling         │
└───────────────────────────┘      └───────────────────────────┘
              │
              ▼
┌───────────────────────────┐      ┌───────────────────────────┐
│ 5. Regulatory approval &  │ ───> │ 6. Longitudinal MRD       │
│    reimbursement          │      │    monitoring              │
└───────────────────────────┘      └───────────────────────────┘

Stage 1: Blood draw and cfDNA extraction

A standard venous blood draw is processed to isolate cell-free DNA from plasma, enriching the small tumor-derived ctDNA fraction shed by dying tumor cells into circulation.

Stage 2: Library prep and NGS / digital PCR

The cfDNA is converted into a sequencing library and run on a broad NGS panel (Guardant360, FoundationOne Liquid CDx) or a targeted digital-PCR/NGS assay (Sysmex Inostics PlasmaSeqSensei), for MRD tests referenced against a tumor-informed patient-specific variant baseline (Signatera, FoundationOneMRD).

Stage 3: Bioinformatics and variant calling

Specialised algorithms suppress sequencing background error to call true low-allele-fraction tumor variants, the step that determines assay sensitivity for both companion-diagnostic mutation calling and trace-level MRD detection.

Stage 4: Companion-diagnostic and MRD report

The clinical report either matches detected mutations to an FDA/NMPA-approved targeted therapy (companion-diagnostic use) or reports a positive/negative molecular-residual-disease call relative to the patient’s treatment timeline.

Stage 5: Regulatory approval and reimbursement

The assay is approved as an FDA PMA companion diagnostic, certified under EU IVDR 2017/746, or registered as an NMPA in-vitro diagnostic device, with payer coverage typically following the regulatory approval and published clinical-utility evidence.

Stage 6: Longitudinal MRD monitoring

Serial post-treatment blood draws track the ctDNA trend over months to years, providing recurrence-risk surveillance (Signatera, FoundationOneMRD) that can lead imaging by months in published clinical studies.