Zane Baird

Lipid and metabolite profiles of human brain tumors by desorption electrospray ionization-MS

Significance Brain tumors can lead to a significant source of morbidity and mortality. The primary treatment is microsurgical resection, and the extent of resection is associated with length of survival. Unfortunately, reliable intraoperative tools for diagnosis and safe maximal resection of the tumor mass are lacking. Mass spectra (lipid and metabolite profiles) can be used to distinguish between healthy and diseased tissues by comparison of patterns of peak intensities using multivariate statistics. This experiment can be done on a timescale amenable to intraoperative analysis using tissue smears. These data can provide surgeons with near real-time pathologic information and guide the intraoperative resection of the tumor at the difficult to detect peritumoral borders. Examination of tissue sections using desorption electrospray ionization (DESI)-MS revealed phospholipid-derived signals that differ between gray matter, white matter, gliomas, meningiomas, and pituitary tumors, allowing their ready discrimination by multivariate statistics. A set of lower mass signals, some corresponding to oncometabolites, including 2-hydroxyglutaric acid and N-acetyl-aspartic acid, was also observed in the DESI mass spectra, and these data further assisted in discrimination between brain parenchyma and gliomas. The combined information from the lipid and metabolite MS profiles recorded by DESI-MS and explored using multivariate statistics allowed successful differentiation of gray matter (n = 223), white matter (n = 66), gliomas (n = 158), meningiomas (n = 111), and pituitary tumors (n = 154) from 58 patients. A linear discriminant model used to distinguish brain parenchyma and gliomas yielded an overall sensitivity of 97.4% and a specificity of 98.5%. Furthermore, a discriminant model was created for tumor types (i.e., glioma, meningioma, and pituitary), which were discriminated with an overall sensitivity of 99.4% and a specificity of 99.7%. Unsupervised multivariate statistics were used to explore the chemical differences between anatomical regions of brain parenchyma and secondary infiltration. Infiltration of gliomas into normal tissue can be detected by DESI-MS. One hurdle to implementation of DESI-MS intraoperatively is the need for tissue freezing and sectioning, which we address by analyzing smeared biopsy tissue. Tissue smears are shown to give the same chemical information as tissue sections, eliminating the need for sectioning before MS analysis. These results lay the foundation for implementation of intraoperative DESI-MS evaluation of tissue smears for rapid diagnosis.

Using Ambient Ion Beams to Write Nanostructured Patterns for Surface Enhanced Raman Spectroscopy

Electrolytic spray deposition was used to pattern surfaces with 2D metallic nanostructures. Spots that contain silver nanoparticles (AgNP) were created by landing solvated silver ions at desired locations using electrically floated masks to focus the metal ions to an area as little as 20 μm in diameter. The AgNPs formed are unprotected and their aggregates can be used for surface-enhanced Raman spectroscopy (SERS). The morphology and SERS activity of the NP structures were controlled by the surface coverage of landed silver ions. The NP structures created could be used as substrates onto which SERS samples were deposited or prepared directly on top of predeposited samples of interest. The evenly distributed hot spots in the micron-sized aggregates had an average SERS enhancement factor of 10(8) . The surfaces showed SERS activity when using lasers of different wavelengths (532, 633, and 785 nm) and were stable in air.

Ion Separation in Air Using a Three-Dimensional Printed Ion Mobility Spectrometer

The performance of a small, plastic drift tube ion mobility spectrometer (DT-IMS) is described. The IMS was manufactured using three-dimensional (3D) printing techniques and operates in the open air at ambient pressure, temperature, and humidity. The IMS housing and electrodes were printed from nonconductive polylactic acid (PLA, housing) and conductive polyethylene terephthalate glycol-modified polymer containing multiwalled carbon nanotubes (PETG-CNT, electrodes). Ring electrodes consisting of both an inner disk and an outer ring were used to prevent neutral transmission while maximizing ion transmission. As a stand-alone instrument, the 3D printed IMS is shown to achieve resolving powers of between 24 and 50 in positive ion mode using tetraalkylammonium bromide salts (TAA), benzylamines (mono-, di-, and tri-), and illicit drugs (MA, MDEA, and haloperidol). Resolving powers of between 29 and 42 were achieved in negative ion mode using sodium alkyl sulfates (C8, C12, C16, and C18). Reduced ion mobilities of TAA cations (C2-C8) were calculated at 14% relative humidity in air to be 1.36, 1.18, 1.03, 0.90, 0.80, 0.73, and 0.67, respectively. The effect of humidity on reduced ion mobilities of TAA cations is discussed. 3D printing is shown to be a quick and cost-effective way to produce small IMS instruments that can compete in performance with conventionally manufactured IMS instruments that also operate in the open air. An important difference between this IMS and other instruments is the absence of a counter gas flow.

Outlook and Future Directions

While a brief introduction to the FDM process was provided in Sect. 1.4, a more detailed overview of the components, kinematics, and figures of merit of different types of 3D printers is warranted. In general, a 3D printer must include: (i) a platform on which the object is to be built, (ii) a means of additive delivery of material in a controlled manner, and (iii) accurate and precise control of positioning in at least 3 axes. These requirements can be addressed by several approaches with trade-offs in cost and performance.

Ion Manipulation in Air Using a System of Curved 3D Printed Plastic Electrodes

Mass spectrometry (MS) is arguably one of the most widely used scientific tools with applications ranging from complex mixture analysis (Cooks et al. in Int. J. Mass Spectrom. 377:709–718, 2014 [1], Kojo in High-Throughput Analysis in the Pharmaceutical Industry, CRC Press, Boca Raton, pp. 377–391, 2008 [2]) to molecular biology (Aebersold and Mann in Nature 422:198–207, 2003 [3]) and even large-scale purification and materials preparation (Parkins in Phys. Today 58:45–51, 2005 [4], Johnson et al. Ann. Rev. Anal. Chem. 4:83–104, 2011 5]). Because the fundamental basis for MS relies on a low number of collisions, the operation of a mass spectrometer requires the establishment of a low pressure environment.

3D Printed Annular Focusing Ambient Ion Mobility Spectrometer

From its beginnings as “Plasma Chromatography™” for the analysis of trace organic molecules, to applications in security for the detection of explosives and chemical warfare agents, and more recent applications in structural analysis of biomolecules, ion mobility spectrometry (IMS) has been demonstrated as a powerful analytical tool.

Tumor Cell Detection by Mass Spectrometry Using Signal Ion Emission Reactive Release Amplification.

A method is presented for the detection of circulating tumor cells (CTC) using mass spectrometry (MS), through reporter-ion amplification. Particles functionalized with short-chain peptides are bound to cells through antibody-antigen interactions. Selective release and MS detection of peptides is shown to detect as few as 690 cells isolated from a 10 mL blood sample. Here we present proof-of-concept results that pave the way for further investigations.