The MasSpec Pen is a mass spectrometry (MS) based cancer detection and diagnosis system that can be used for ex vivo and in vivo tissue sample analysis. The system collects biological molecules from a tissue sample surface via a solid-liquid extraction mechanism and transports the molecules to a mass spectrometer for analysis. The composition of the extracted molecules can then be used to predict if the tissue sample analyzed contains cancerous cells using machine learning algorithms and statistical models. In early-stage clinical research, the MasSpec Pen system was able to distinguish various cancer tissues, including thyroid, breast, lung, and ovarian tumor tissues, from their normal counterparts with an overall accuracy of 96.3%. A follow-up study in illustrating the use of the device for detection of serous ovarian carcinoma in ex vivo tissue biopsies allowed for the discrimination of normal and cancerous ovarian samples with a clinical sensitivity and specificity of 94.0% and 94.4%, respectively.
Development and current usage Livia S. Eberlin, Ph.D., an Assistant Professor of Chemistry at the University of Texas at Austin, first reported the invention of the MasSpec Pen in 2017. Within her laboratory, the device has been used to analyze human tissue biopsies, including normal and cancerous breast, lung, ovarian, and thyroid samples. The MasSpec Pen is currently being evaluated for use on freshly excised tissue biopsies and for intraoperative use during oncology surgeries. The MasSpec Pen has been licensed to Genio Technologies, Inc., a subsidiary of MS Pen Technologies, Inc.
Principle of operation
Ambient ionization mass spectrometry for disease diagnosis The MasSpec Pen technology is based on the principles of ambient ionization, in which ions are generated directly from a sample without need for extensive sample preparation or chromatographic separations. The MasSpec Pen can further be categorized as a solid-liquid extraction based ambient ionization method, described as methods that utilize a solvent system to gently extract molecules from a sample surface that are subsequently analyzed by a mass spectrometer. Desorption electrospray ionization (DESI) was the first liquid-based ambient ionization MS method. DESI employed a spray of charged solvent droplets to bombard a sample surface to desorb and ionize molecules from the sample surface, which are then directed towards and analyzed by a mass spectrometer. DESI-MS and other solvent-based ambient ionization MS methods has been widely employed for the analysis of small molecules, primarily metabolites and lipids, directly from biological tissue specimens to determine their molecular composition and leverage the mass spectral data acquired for diagnostic purposes. These methods have been deployed for the discrimination of normal and cancerous regions of tissue samples for many solid tumor indications, including breast, brain, prostate, ovarian, and colorectal, among others. Multivariate statistical analysis methods are often utilized to generate statistical models from the mass spectral data acquired from direct analysis of tissue samples to distinguish between healthy and diseased tissues.
MasSpec Pen analysis mechanism The MasSpec Pen, initially described in 2017, is a solvent-based ambient ionization technique but differs from its predecessors due to the handheld nature of the device, allowing analysis of samples distant from the mass spectrometer in a geometry independent manner. The MasSpec Pen used a probe that can be manipulated by hand to direct the analysis. To use the system, the tip of the 'pen' is placed in contact with the surface to be sampled and the user triggers the initiation of a sampling procedure by pressing an integrated foot pedal. This signals a syringe pump to deliver a small aliquot of solvent through a polymer tube to a reservoir at the tip of the 'pen' that remains in contact with the sample. Analytes are then extracted from the sample into the solvent droplet by a solid-liquid extraction mechanism. After a 3 second extraction period, the droplet is aspirated into the mass spectrometer using the vacuum from the mass spectrometer as the vacuum source. Once inside the mass spectrometer, the analytes within the solvent droplet are de-solvated and ionized via an inlet ionization mechanism. The ionized molecules are then analyzed by the mass spectrometer analyzer and the mass spectrum resulting is generated.
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