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Introduction to Cancer
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Intraoperative molecular-based tests are also being introduced to prevent the need for follow-up surgery after an initial operation to remove a tumor. In 2013 the UK’s National Institute for Health and Care Excellence (NICE) recommended a new test, the RD-100i OSNA (One-Step Nucleic Acid Amplification) System developed by the Japanese healthcare company Sysmex, for use in the NHS during breast cancer surgery to determine whether the cancer has spread to lymph nodes in the armpit (see Chapter 11). Before this, women diagnosed with early-stage invasive breast cancer had to undergo a biopsy of their lymph nodes during initial surgery to remove tumors in the breast tissue, and then wait up to three weeks for the results, with a second operation required if further disease was found. The RD-100i OSNA test means that surgeons can establish whether the cancer has spread during the initial surgery, and then remove the lymph nodes if necessary, during the same operation. This means that many patients will require fewer operations, thus reducing anxiety and distress, and the costs of surgery. Importantly, the faster diagnosis means that other treatments such as chemotherapy and radiotherapy can be started more rapidly. With a similar goal, researchers at the University of Texas at Austin (USA) are developing a hand-held device coupled to a mass spectrometer known as the MasSpec Pen which uses a discrete water droplet for molecular extraction and rapid tissue diagnosis during surgery.
Emerging Biomedical Analysis
Published in Lawrence S. Chan, William C. Tang, Engineering-Medicine, 2019
As recently reported, scientists at the University of Texas at Austin, led by Livia Eberlin, Associate Professor of Chemistry, have developed a handheld mass spectrometry device that can identify cancer in near real-time. Using this “MasSpec Pen,” which connects to a mass spectrometry instrument, surgeons can easily search residual cancer at the surgical margin and adjacent tissues during their cancer surgeries within seconds. More importantly, the process does not cause tissue damage that may become a physical healing problem and an ethical concern (Waltz 2017, Zhang et al. 2017). The step-by-step intraoperative procedure of this “MasSpec Pen” is described below (Waltz 2017): The operating surgeon holds the “MasSpec Pen” against the questionable tissue in vivo.Water-soluble molecules, including tumor-specific metabolites, are dissolved by the water droplets suspended at the tip of the “MasSpec Pen”.Dissolved and ionized molecules in the droplet travel to the MS for analysis.The molecular information, the mass-to-charge ratio representing the quantitative relationship between mass and electrical charge that is unique for each molecule, is identified.The identified data is analyzed by a statistical classifier that is trained and validated with hundreds of histopathology-certified cancer and normal tissue samples and will determine and report if the questionable tissue is cancerous or normal, within seconds, with greater than 95% accuracy.The surgeon makes an intraoperative decision depending on the finding by the “MasSpec pen”.
Proteomics and pulse azidohomoalanine labeling of newly synthesized proteins: what are the potential applications?
Published in Expert Review of Proteomics, 2018
Tissue diagnosis is particularly important for the determination of cancer grades, and especially for surgical margin evaluation during surgery excision of cancer patients. For decades, diagnosis of tissue samples in the clinical environment has been performed by skilled pathologists using light microscopy techniques [100]. Of late, MS imaging (MSI) has gained increased attention from the biological and medical communities as a powerful approach for tissue imaging and diagnosis. MALDI imaging has provided great hope for tissue analysis by MS, but it requires matrix application to tissue samples and analysis under vacuum conditions [101]. Several ambient ionization MS techniques have been developed for rapid molecular diagnosis of cancer tissues and have shown exceptional potential for clinical use [102]. These ambient ionization MS strategies allow sample analysis in an open environment at atmospheric pressure. More recently, an automated, biocompatible and disposable handheld device called the MasSpec Pen have been developed for direct, real-time nondestructive sampling and molecular diagnosis of tissues [103].
Insights and prospects for ion mobility-mass spectrometry in clinical chemistry
Published in Expert Review of Proteomics, 2022
David C. Koomen, Jody C. May, John A. McLean
To assess disease state by detecting tumor margins in cancerous tissues, three MS tools with distinct delivery systems have recently been developed and deployed in the clinic: desorption electrospray ionization-MS (DESI-MS), the MasSpec Pen and the intelligent knife (iKnife). DESI-MS has been demonstrated in typically ex vivo contexts to map cancerous tumor margins in pathological tissue samples [92,107,108]. First described in 2004, DESI directs charged droplets derived from an electrospray ion source onto a tissue. Through analyte extraction and secondary droplet formation, the analyte species brought to the surface of the tissue are directed into the mass spectrometer. The MasSpec pen utilizes a principle similar to a liquid microjunction surface sampling probe (LMJ-SSP) described by Van Berkel and colleagues for planar surfaces. In the LMJ-SSP a continuously flowing coaxial solvent is directed to a surface via a microjunction for micro liquid extraction of analytes. The extracted analytes are then coaxially directed into the ion source (most commonly ESI) of the MS [109–111]. Rather than a continuous solvent flow, the MasSpec pen uses the gas displacement of user defined single droplets for analyte extraction (Figure 4(A)) [112]. This hand-held, liquid-delivery auxiliary tool coupled to MS can be used for real-time biochemical analysis during surgical procedures [100]. The MasSpec Pen allows for rapid, nondestructive molecular analysis to diagnose abnormal tissues. While intraoperative spectroscopic analyses such as Raman have previously been demonstrated for real-time biochemical analysis during surgery, the MasSpec Pen can collect MS-derived molecular information for disease biomarkers in tissue [112–115]. For example, intraoperative detection of abnormal tissue types can be assessed in ambient conditions by measuring certain onco-metabolites such as 2-hydroxyglutarate in glioma tissue [116]. Additionally, tumor margins can be assessed with the MasSpec pen in thyroid carcinoma (Figure 4(B)) [112]. Elevated abundances of lipid species in the m/z 700–900 range indicate the disease state of the tissue. Among the changes in the metabolic profile of the thyroid carcinoma there is a higher abundance of phosphatidyl inositol (m/z 885), which allows the clinician to determine tumor margins in real-time. While the surgical operation itself is invasive, the MasSpec Pen analysis utilizes discrete water droplets that are nondestructive, which allows for normal tissue to remain intact, improving decision-making by the surgeon, and subsequently, the efficiency of the surgical procedure.