The Intelligent Knife (iKnife): Revolutionizing Intraoperative Tissue Diagnosis Through Rapid Evaporative Ionization Mass Spectrometry (REIMS)

The intelligent surgical knife (iKnife), based on rapid evaporative ionization mass spectrometry (REIMS), represents a transformative advance in intraoperative tissue characterization. By integrating mass spectrometry with electrosurgical dissection, the iKnife enables real-time differentiation between cancerous and healthy tissues through molecular fingerprinting of the aerosol generated during cutting. This innovation significantly shortens operative time by eliminating delays associated with conventional histopathological analysis and enhances surgical precision by providing continuous feedback on tissue composition. Since its inception by Zoltán Takáts and colleagues, the iKnife has demonstrated remarkable diagnostic accuracy across multiple cancer types, including breast, ovarian, and colorectal malignancies, with reported sensitivities and specificities > 90% in selected tumour types. Beyond oncology, REIMS technology also shows promise for microbial identification and metabolomic profiling. This review provides a comprehensive overview of the iKnife’s development, underlying principles, clinical validation, and emerging applications, as well as its integration into surgical workflows and the challenges remaining for widespread clinical adoption. Future perspectives include miniaturization, AI-driven spectral interpretation, and expansion into robotic and image-guided surgery.