Intraoperative molecular diagnostics

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.

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.