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

Abstract

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.

Is the Pen really Mightier than the Scalpel?

“…It is capable of identifying histologically distinct regions in a single human tissue sample. 3 These results show that the MasSpec pen can be used to detect cancer in margins with mixed composition of normal and cancer cells by the molecular information obtained. Thus, this recent technology in the diagnosis of cancer can be exploited for oral squamous cell carcinoma (OSCC) detection, diagnosis, and assessment.…”

“…But the technology relies on tissue damage to produce molecular ions. [2][3][4] Along with this, the major concern is that the electrosurgical smoke contains irritants, carcinogens, and neurotoxic compounds. Exposure to these compounds may cause health hazards.…”

“…3 The chemical information is obtained directly from the tissue samples. It has a greater advantage of being used for clinical or field application, as it is portable.…”

“…6 The major drawback of this technique is that it cannot be used for in vivo analysis as it includes use of organic solvent sprays, high-pressure nebulizing gas, and high voltages. 3,7,8 It is also known to have lower spatial resolution (180-200 μm). 6 The MS coupled with ultraviolet lasers and infrared lasers is a laser desorption ionization (LDI)-MS analysis.…”

“…It has been reported that the database allows prediction of malignancy with a high sensitivity (96.4%), specificity (96.2%), and a good overall precision (96.3%). 3 All the components are incorporated within the tip so the geometrical optimization and alignment is not required. The pen has three primary components: syringe pump, polytetrafluoroethylene tubing conduits, and a sampling probe.…”