Intraoperative molecular diagnostics

01Overview and value chain

Markers: [EC: IVDR 2017/746 + MDR 2017/745 | OECD: Biotech-health | Regulator: FDA (USA), EMA (European Union), NMPA (China)]

Intraoperative molecular diagnostics give surgeons a real-time read on tissue identity — tumor versus healthy margin — during the operation itself, replacing or supplementing the decades-old workflow of sending a frozen section to pathology and waiting 20-30 minutes for a result. On Target Laboratories’ Cytalux (pafolacianine) is an FDA-approved folate-receptor-targeted fluorescence imaging agent that helps surgeons visualize malignant tissue during cancer surgery, and has now been used in over 1,000 real-world cancer surgeries with outcomes tracking its clinical-trial data. Dilon Technologies received FDA approval and launched MarginProbe 2, a next-generation radiofrequency-spectroscopy probe for intraoperative breast-tumor margin assessment during breast-conserving surgery. Perimeter Medical Imaging AI’s Claire became the first FDA-approved AI-enabled optical coherence tomography (OCT) imaging device for breast-cancer-surgery margin assessment. Invenio Imaging’s stimulated Raman histology (SRH) system generates digital, pathologist-quality histopathology images of brain-tumor tissue in the operating room without the frozen-section stains and delay. In Europe, photonamic’s Gliolan (Gleolan in the US, 5-aminolevulinic acid) is a fluorescence-guided-resection agent that makes glioma tissue fluoresce under blue light during surgery, and Imperial College London’s iKnife (rapid evaporative ionization mass spectrometry, REIMS) analyzes the smoke generated by electrosurgical cutting in real time to identify tissue type, commercialized in partnership with Waters Corporation.

The key directions of intraoperative molecular diagnostics are:

1. Fluorescence-guided surgery (Fluorescence-Guided Surgery): imaging agents that make tumor tissue visibly fluoresce under specific light during the operation — Cytalux (folate-receptor-targeted), Gliolan/Gleolan (5-ALA, glioma).
2. Optical margin imaging (Optical Coherence Tomography): high-resolution optical scanning of the excised specimen surface for margin assessment without tissue destruction — Perimeter Medical Imaging AI’s Claire.
3. Digital intraoperative histopathology (Stimulated Raman Histology): label-free optical microscopy generating pathologist-quality tissue images in minutes instead of the 20-30 minute frozen-section workflow — Invenio Imaging.
4. Mass-spectrometry and RF-spectroscopy tissue ID (Rapid Evaporative Ionization Mass Spectrometry): real-time chemical/electrical tissue-type identification during cutting or probing — Imperial College London’s iKnife (REIMS), Dilon Technologies’ MarginProbe (RF spectroscopy).

Sectoral value chain

[agent/probe/system development] ──> [FDA/CE regulatory approval] ──> [OR integration & surgeon training]
                                                    │
                                       (real-time intraoperative tissue analysis)
                                                    │
                                                    ▼
[guideline adoption & post-market evidence] <─── [surgical margin/resection decision] <─────┘

Value chain levels

Cross-cutting technologies of the sector:

• Fluorescence-guided surgery (Fluorescence-Guided Surgery): targeted or accumulation-based fluorescent agents (folate-receptor conjugates, 5-ALA) make tumor tissue visibly distinct from healthy tissue under specific-wavelength light.
• Stimulated Raman histology (Stimulated Raman Histology): label-free Raman-scattering microscopy generates virtual H&E-equivalent tissue images without the stains, sectioning and 20-30-minute wait of frozen-section pathology.
• Rapid evaporative ionization mass spectrometry (Rapid Evaporative Ionization Mass Spectrometry): analyzes the aerosol/smoke generated by electrosurgical cutting to identify tissue type from its lipidomic profile in near-real time.

02US

The US hosts the deepest bench of intraoperative diagnostic device and agent makers, spanning fluorescence agents, OCT imaging and digital histopathology, all under FDA device/drug approval pathways.

Cytalux, MarginProbe 2, Claire, NIo

• On Target Laboratories: Cytalux (pafolacianine) is an FDA-approved folate-receptor-targeted fluorescence imaging agent used to help surgeons visualize malignant tissue during cancer surgery, with real-world outcome data now tracking its original clinical-trial findings across more than 1,000 surgeries.
• Dilon Technologies: received FDA approval and launched MarginProbe 2, a next-generation radiofrequency-spectroscopy probe for intraoperative breast-tumor margin assessment in breast-conserving surgery, continuing the MarginProbe technology line through a pivotal trial for the upgraded device.
• Perimeter Medical Imaging AI: Claire is the first FDA-approved AI-enabled optical coherence tomography (OCT) imaging device for breast-cancer-surgery margin assessment, scanning the excised specimen surface without destroying tissue.
• Invenio Imaging: its stimulated Raman histology (SRH) system generates digital, pathologist-quality images of brain-tumor tissue in the operating room, aimed at central-nervous-system surgery where frozen-section turnaround is a bottleneck.
• FDA framework: intraoperative fluorescence agents clear the FDA as new drugs (Cytalux), while imaging and spectroscopy devices clear as PMA/510(k) medical devices (MarginProbe, Claire), with an accelerating cadence of approvals in the category since 2024-2026.

03CN

China’s operating rooms are adopting intraoperative frozen-section and rapid-pathology workflows at scale, but no dedicated Chinese intraoperative molecular-diagnostics company cleared source confirmation as a distinct commercial originator in this category as of 2026.

rapid pathology, NMPA, technology transfer

• Domestic frozen-section capacity: major Chinese oncology centers run high-volume conventional frozen-section pathology, the workflow this category’s fluorescence, OCT and Raman-histology technologies aim to speed up or replace.
• Import and technology-transfer pathway: US and EU intraoperative diagnostic agents and devices (fluorescence agents, OCT systems) typically enter China via NMPA import registration or local distribution partnerships rather than domestic-originated platforms at this stage.
• NMPA framework: intraoperative diagnostic devices and any companion in-vitro diagnostic component register under NMPA as medical devices/IVD products, following the same device-class pathway as imported fluorescence and OCT systems.

04EU

Europe’s contribution centers on a fluorescence-guided-resection drug for brain-tumor surgery and the mass-spectrometry iKnife technology pioneered at Imperial College London.

Gliolan/Gleolan, iKnife, MDR/IVDR

• photonamic (Germany, medac Group): markets Gliolan (Gleolan in the US), a 5-aminolevulinic acid (5-ALA) agent that patients take before glioma surgery so that tumor tissue fluoresces under blue light, letting neurosurgeons achieve more complete resections than white-light surgery alone.
• Imperial College London: developed the iKnife (Intelligent Knife), which uses rapid evaporative ionization mass spectrometry (REIMS) to analyze the aerosol generated by electrosurgical cutting in real time and identify tissue type from its lipidomic signature, commercialized in partnership with Waters Corporation’s mass-spectrometry platforms.
• MDR/IVDR framework: intraoperative devices and companion in-vitro diagnostic elements sold in the EU fall under the Medical Device Regulation (MDR 2017/745) and, where a diagnostic assay component is involved, the In Vitro Diagnostic Regulation (IVDR 2017/746).

05Leading companies and research institutes

06Tech stack and innovations

The stack spans four distinct physical principles — targeted fluorescence, optical coherence tomography, Raman scattering and mass spectrometry — each converted into a real-time, OR-compatible readout of tissue identity.

1. Fluorescence imaging agents (Fluorescence-Guided Surgery):
   • Cytalux binds folate receptors overexpressed on many tumor cells, and Gliolan/Gleolan’s 5-ALA is metabolized into a fluorescent porphyrin preferentially by glioma tissue, both making tumor visibly distinct under specific-wavelength light without any additional imaging hardware in the room.
2. AI-enabled optical coherence tomography (Optical Coherence Tomography):
   • Perimeter Medical Imaging AI’s Claire scans the excised specimen surface with OCT and an AI interpretation layer to flag positive margins, a non-destructive optical alternative to frozen-section sampling.
3. Stimulated Raman histology (Stimulated Raman Histology):
   • Invenio Imaging’s system illuminates unstained fresh tissue with two lasers tuned to the Raman scattering signature of lipids and proteins, computationally rendering a virtual H&E-equivalent image in minutes.
4. Mass-spectrometry and RF-spectroscopy tissue ID (Rapid Evaporative Ionization Mass Spectrometry):
   • Imperial College London’s iKnife feeds electrosurgical smoke into a mass spectrometer (via Waters Corporation’s platform) for lipidomic tissue-type classification, while Dilon Technologies’ MarginProbe measures the electrical/RF response of tissue in direct probe contact — two different physical routes to the same real-time tissue-ID goal.

07Value chains and production pipelines

Industrial pipeline of an intraoperative molecular diagnostic (FDA PMA/510(k) / EU MDR-IVDR)

┌───────────────────────────┐      ┌───────────────────────────┐
│ 1. Agent/probe/system     │ ───> │ 2. Regulatory approval   │
│    development             │      │                           │
└───────────────────────────┘      └───────────────────────────┘
                                                   │
                                                   ▼
┌───────────────────────────┐      ┌───────────────────────────┐
│ 4. Real-time tissue       │ <─── │ 3. OR integration &      │
│    analysis                │      │    training                │
└───────────────────────────┘      └───────────────────────────┘
              │
              ▼
┌───────────────────────────┐      ┌───────────────────────────┐
│ 5. Surgical decision      │ ───> │ 6. Guideline adoption &  │
│                            │      │    evidence                │
└───────────────────────────┘      └───────────────────────────┘

Stage 1: Agent, probe or system development

A fluorescence agent (folate-receptor conjugate, 5-ALA), an optical/spectroscopic imaging system (OCT, SRH lasers) or a mass-spec/RF-probe interface is developed against the specific physical or biological principle that distinguishes tumor from healthy tissue.

Stage 2: Regulatory approval

Fluorescence agents clear the FDA as new drugs and imaging/spectroscopy devices clear as PMA or 510(k) medical devices in the US, or undergo MDR/IVDR conformity assessment in the EU, each requiring clinical data demonstrating diagnostic accuracy against standard pathology.

Stage 3: OR integration and training

The approved device or agent is installed in the operating room workflow, with surgeons and pathologists trained to interpret the fluorescence, OCT, SRH or mass-spec readout alongside standard surgical judgment.

Stage 4: Real-time tissue analysis

During the procedure, the excised specimen or in-situ tissue is imaged, probed or analyzed — fluorescence visualization, OCT scan, SRH microscopy or REIMS mass-spec/RF-spectroscopy reading — producing a tissue-identity result within the timeframe of the ongoing surgery.

Stage 5: Surgical decision

The surgeon uses the real-time readout to decide whether to extend the resection, conclude the procedure, or send an additional sample to standard frozen-section pathology for confirmation.

Stage 6: Guideline adoption and evidence

Published re-excision-rate reductions and other outcome data (Cytalux’s 1,000+-surgery real-world tracking, Claire’s FDA clearance as the first AI-enabled OCT device) feed surgical-society guideline recommendations and payer coverage decisions.