Ph.D. Candidate, Graduate Student, Rensselaer Polytechnic Institute
Development of multimodal approach to get maximum chemical information from precious samples
Recent advances have led to the ability to generate comprehensive chemical maps of solid samples with high spatial resolution. Unambiguous analyte identification from these samples necessarily requires different analyses performed on the same sample, often termed ‘multimodal chemical imaging’. While tandem imaging methods provide a wealth of information, they often suffer from weak sensitivity, poor selectivity, or compromised spatial resolution as dictated by the spectroscopic method employed. Greater success in comprehensive chemical imaging has been achieved with mass-spectrometry-based instruments, due to the excellent sensitivity and selectivity. Here, we present our recent work towards the development of a multimodal chemical-imaging apparatus capable of providing simultaneous molecular and elemental information from the exact same spatial location at high spatial resolution (30 microns). This dual imaging approach is achieved through laser sampling of samples, at atmospheric pressure, followed by simultaneous mass-spectrometric and optical-emission measurements. Aerosolized particles from the resulting ablation process were swept with a gas stream to a flowing atmospheric-pressure afterglow (FAPA) molecular ionization source and, subsequently, mass-analyzed with an Orbitrap mass analyzer. At the same time, atomic emission from the laser-induced plasma (LIP) formed during the ablation event was recorded to provide elemental information on the laser-sampled area. By Raster scanning the laser across the sample, followed by appropriate data processing, dual atomic and molecular chemical images were generated. The effect of various laser-ablation parameters, such as laser fluence and ablation-gas composition, in conjunction with FAPA operating conditions were explored in detail for a variety of sample types including pharmaceutical tablets, biological tissues, and organic minerals. Different approaches to obtain multimodal atomic and molecular images, as well as the data processing needed to generate and compare chemical images will be presented. Finally, approaches to enable quantitative information for both molecular and atomic analyses will be presented.
Abstract: We report a method that allows a complete quantitative characterization of whole single cells, assessing the total amount of carbon, nitrogen, oxygen, sodium, and magnesium and providing submicrometer maps of element molar concentration, cell density, mass, and volume. This approach allows quantifying elements down to 10(6) atoms/μm(3). This result was obtained by applying a multimodal fusion approach that combines synchrotron radiation microscopy techniques with off-line atomic force microscopy. The method proposed permits us to find the element concentration in addition to the mass fraction and provides a deeper and more complete knowledge of cell composition. We performed measurements on LoVo human colon cancer cells sensitive (LoVo-S) and resistant (LoVo-R) to doxorubicin. The comparison of LoVo-S and LoVo-R revealed different patterns in the maps of Mg concentration with higher values within the nucleus in LoVo-R and in the perinuclear region in LoVo-S cells. This feature was not so evident for the other elements, suggesting that Mg compartmentalization could be a significant trait of the drug-resistant cells.
Pub.: 17 Apr '14, Pinned: 28 Jun '17
Abstract: We demonstrate the coupling of desorption electro-flow focusing ionization (DEFFI) with in-source collision induced dissociation (CID) for the mass spectrometric (MS) detection and imaging of explosive device components, including both inorganic and organic explosives and energetic materials. We utilize in-source CID to enhance ion collisions with atmospheric gas, thereby reducing adducts and minimizing organic contaminants. Optimization of the MS signal response as a function of in-source CID potential demonstrated contrasting trends for the detection of inorganic and organic explosive device components. DEFFI-MS and in-source CID enabled isotopic and molecular speciation of inorganic components, providing further physicochemical information. The developed system facilitated the direct detection and chemical mapping of trace analytes collected with Nomex swabs and spatially resolved distributions within artificial fingerprints from forensic lift tape. The results presented here provide the forensic and security sectors a powerful tool for the detection, chemical imaging, and inorganic speciation of explosives device signatures.
Pub.: 27 Jun '14, Pinned: 28 Jun '17
Abstract: Femtosecond laser ablation/ionization mass spectrometry (LIMS) has been applied to probe the spatial element composition of three ternary Cu–Sn–Pb model bronze alloys (lead bronzes: CuSn10Pb10, CuSn7Pb15, and CuSn5Pb20), which were recently identified as high-performance cathode materials in the context of electro-organic synthesis (dehalogenation, deoxygenation) of pharmaceutically relevant building blocks. The quantitative and spatially resolved element analysis of such cathode materials will help in understanding the observed profound differences in their electrochemical reactivity and stability. For that purpose, we developed a measurement procedure using the LIMS technique which allows analyzing the element composition of these ternary alloys in all three spatial dimensions. Their chemical composition was determined spotwise, by ablating material from various surface locations on a 4 × 4 raster array (50 μm pitch distance, ablation crater diameter of ∼20 μm). The element analyses show significant chemical inhomogeneities in all three ternary bronze alloys with profound local deviations from their nominal bulk compositions and indicate further differences in the nature and origin of these compositional inhomogeneities. In addition, the element analyses showed specific compositional correlations among the major elements (Cu, Sn, and Pb) in these alloys. On selected sample positions minor (Ni, Zn, Ag, and Sb) and trace elements (C, P, Fe, and As) were quantified. These results are in agreement with inductively coupled plasma collision/reaction interface mass spectrometry (ICP–CRI-MS) and laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) reference measurements, thus proving the LIMS depth profiling technique as a powerful alternative methodology to conventional quantification techniques with the advantage, however, of a highly localized measurement capability.
Pub.: 04 Jan '17, Pinned: 28 Jun '17
Abstract: The inherent difficulty of discovering new and effective antibacterials and the rapid development of resistance particularly in Gram-negative bacteria, illustrates the urgent need for new methods that enable rational drug design. Here we report the development of 3D imaging cluster secondary ion mass spectrometry (SIMS) as a label-free approach to chemically map small molecules in aggregated and single Escherichia coli cells, with ~300 nm spatial resolution and high chemical sensitivity. The feasibility of quantitative analysis was explored, and a non-linear relationship between treatment dose and signal for tetracycline and ampicillin, two clinically-used antibacterials, was observed. The methodology was further validated by the observation of reduction in tetracycline accumulation in an E. coli strain expressing the tetracycline-specific efflux pump (TetA) compared to the isogenic control. This study serves as a proof-of-concept for a new strategy for chemical imaging at the nano-scale and has the potential to aid discovery of new antibacterials.
Pub.: 24 Mar '17, Pinned: 28 Jun '17
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