In vivo Real-Time Mass Spectrometry for Guided Surgery Application

Fatou, Benoit; Saudemont, Philippe; Leblanc, Éric; Vinatier, D.; Mesdag, Violette; Wisztorski, Maxence; Focşa, Cristian; Salzet, Michel; Ziskind, Michaël; Fournier, Isabelle

doi:10.1038/srep25919

Cited by 118 publications

(133 citation statements)

References 37 publications

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“…For example, a sampling probe using a DESI-MSI source to produce a continuous high-pressure spray of microdroplets has been proposed for tissue analysis (38), but it has not been demonstrated for cancer diagnosis or in vivo use. Ultraviolet and infrared laser approaches have been reported for tissue analysis through ablation processes (23, 24). A resonant infrared laser ablation system was used to analyze a cancer tissue sample ex vivo and human finger skin in vivo (24).…”

Section: Discussionmentioning

confidence: 99%

“…Ultraviolet and infrared laser approaches have been reported for tissue analysis through ablation processes (23, 24). A resonant infrared laser ablation system was used to analyze a cancer tissue sample ex vivo and human finger skin in vivo (24). To date, the iKnife has been the most successful MS-based technique demonstrated for in vivo, intraoperative diagnosis (21, 22).…”

Section: Discussionmentioning

confidence: 99%

“…Rapid evaporative ionization MS, or the iKnife, combines an electrocauterization device with MS for direct tissue analysis and classification and has been successfully used intraoperatively for in vivo cancer diagnosis (21, 22). Ultraviolet and infrared lasers have also been coupled with MS for characterization of cancer tissues (23, 24). Although these approaches offer the advantage of incorporating common surgical methods into an MS-based diagnostic workflow, these technologies rely on tissue damage to produce molecular ions or are operationally constrained to a specific surgical modality.…”

Section: Introductionmentioning

confidence: 99%

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Nondestructive tissue analysis for ex vivo and in vivo cancer diagnosis using a handheld mass spectrometry system

et al. 2017

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Conventional methods for histopathologic tissue diagnosis are labor- and time-intensive and can delay decision-making during diagnostic and therapeutic procedures. We report the development of an automated and biocompatible handheld mass spectrometry device for rapid and nondestructive diagnosis of human cancer tissues. The device, named MasSpec Pen, enables controlled and automated delivery of a discrete water droplet to a tissue surface for efficient extraction of biomolecules. We used the MasSpec Pen for ex vivo molecular analysis of 20 human cancer thin tissue sections and 253 human patient tissue samples including normal and cancerous tissues from breast, lung, thyroid, and ovary. The mass spectra obtained presented rich molecular profiles characterized by a variety of potential cancer biomarkers identified as metabolites, lipids, and proteins. Statistical classifiers built from the histologically validated molecular database allowed cancer prediction with high sensitivity (96.4%), specificity (96.2%), and overall accuracy (96.3%), as well as prediction of benign and malignant thyroid tumors and different histologic subtypes of lung cancer. Notably, our classifier allowed accurate diagnosis of cancer in marginal tumor regions presenting mixed histologic composition. Last, we demonstrate that the MasSpec Pen is suited for in vivo cancer diagnosis during surgery performed in tumor-bearing mouse models, without causing any observable tissue harm or stress to the animal. Our results provide evidence that the MasSpec Pen could potentially be used as a clinical and intraoperative technology for ex vivo and in vivo cancer diagnosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nondestructive tissue analysis for ex vivo and in vivo cancer diagnosis using a handheld mass spectrometry system

et al. 2017

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“…Dynamics of ions emission are important to study for a wide spectrum of applications either medical1, industrial or academic, such as pulsed laser deposition2, laser induced breakdown spectroscopy3, laser assisted mass spectrometry4, ion implantation5, and light source generation6. With nanosecond pulsed lasers, the ablation of metals is accompanied by large-heat affected zones, as well as the formation and ejection of molten material78.…”

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confidence: 99%

Characteristics of Ions Emission from Ultrashort Laser Produced Plasma

Elsied

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Diwakar

et al. 2016

Sci Rep

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The dynamic characteristics of the ions emitted from ultrashort laser interaction with materials were studied. A series of successive experiments were conducted for six different elements (C, Al, Cu, Mo, Gd, and W) using 40 fs, 800 nm Ti: Sapphire laser. Time-of-flight (TOF) ion profile was analyzed and charge emission dependencies were investigated. The effects of incident laser interaction with each element were studied over a wide range of laser fluences (0.8 J/cm2 to 24 J/cm2) corresponding to laser intensities (2.0 × 1013 W/cm2 to 6.0 × 1014 W/cm2). The dependencies of the angular resolved ion flux and energy were also investigated. The TOF ion profile exhibits two peaks corresponding to a fast and a slow ion regime. The slow ions emission was the result of thermal vaporization while fast ions emission was due to time dependent ambipolar electric field. A theoretical model is proposed to predict the total ion flux emitted during femtosecond laser interaction that depends on laser parameters, material properties, and plume hydrodynamics. Incident laser fluence directly impacts average charge state and in turn affects the ion flux. Slow ions velocity exhibited different behavior from fast ions velocity. The fast ions energy and flux were found to be more collimated.

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“…It causes tissue damage to produce molecular ions for in vivo diagnosis. 9,10 The method is likewise operationally compelled to a particular surgical methodology. There is a local rise in temperature and the structural proteins are precipitated Editorial as the laser energy is absorbed by the tissue, which eventually causes boiling of the water content of tissue.…”

mentioning

confidence: 99%