# Liquid biopsy & ctDNA diagnostics
Blood-based detection and quantification of circulating tumor DNA (ctDNA) for cancer companion diagnostics and molecular residual disease (MRD) monitoring, replacing or supplementing tissue biopsy — led by Guardant Health, Natera and Foundation Medicine in the US, Sysmex Inostics in the EU, MedGenome in India, and Burning Rock Biotech in China.
Source: https://en.bioecon.ru/technology/liquid-biopsy-ctdna-diagnostics/
Updated: 2026-08-18
## Overview 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
| Level | Description | Key inputs/outputs |
|:---|:---|:---|
| **Blood Draw & Extraction** | cell-free DNA (cfDNA) isolation from plasma, enriching the tumor-derived ctDNA fraction | **In:** patient blood sample.
**Out:** purified cfDNA. |
| **Library Prep & Detection** | NGS library construction or digital-PCR assay against cfDNA, targeting cancer-relevant genes/variants | **In:** cfDNA, tumor-informed baseline (for MRD).
**Out:** raw sequence/PCR data. |
| **Bioinformatics & Variant Calling** | low-frequency variant calling, background-error suppression, MRD signal algorithms | **In:** raw sequence data.
**Out:** variant/MRD call. |
| **Companion-diagnostic / MRD Report** | clinical report matching mutations to approved therapies or flagging molecular recurrence | **In:** variant calls.
**Out:** actionable clinical report. |
| **Regulatory Approval & Reimbursement** | FDA PMA/CDx approval, EU IVDR certification, NMPA registration, payer coverage | **In:** clinical validation data.
**Out:** approved, reimbursed test. |
| **Longitudinal MRD Monitoring** | serial post-treatment blood draws tracking ctDNA trend for recurrence surveillance | **In:** serial samples.
**Out:** recurrence-risk trend. |
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.
---
## US
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.
---
## CN
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.
---
## EU
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.
---
## Leading companies and research institutes
| Company / Institute | Country | Key products / platforms | Tech features | Status 2026 |
|:---|:---|:---|:---|:---|
| **Guardant Health** | 🇺🇸 USA | *Guardant360 CDx / Liquid CDx* | FDA CDx, 100x-expanded panel | commercial |
| **Natera** | 🇺🇸 USA | *Signatera MRD / CDx* | IVDR-certified, FDA CDx (MIBC) | commercial |
| **Foundation Medicine** | 🇺🇸 USA | *FoundationOne CDx / Liquid CDx / MRD* | Multiple stacked FDA CDx approvals | commercial |
| **Sysmex Inostics** | 🇩🇪 Germany | *PlasmaSeqSensei NGS kits* | Targeted panels, HPV-Seq | commercial |
| **MedGenome** | 🇮🇳 India | *Oncology genomics / ctDNA research* | Biomarker research & services | growth |
| **Burning Rock Biotech** | 🇨🇳 China | *NGS ctDNA solid-tumor panels* | Nasdaq-listed (BNR) | commercial |
---
## Tech 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.
---
## Value 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.