MeV-SIMS is an emerging mass spectrometry imaging method that employs fast, heavy ions to desorb secondary molecules from the analyzed sample. High yields and low fragmentation rates of large ...molecules, associated with the dominating electronic sputtering process, make it particularly useful in biomedical research, where insight into the distribution of organic molecules is vital. Both yield and fragmentation of desorbed molecules in MeV-SIMS rely on characteristics of the primary ion but may also be impaired by poor instrumental settings. After utilizing secondary ion optics in the linear mass spectrometer at the micro-analytical center of the Jožef Stefan Institute, we demonstrate very efficient detection of secondary ions. As a result, the secondary ion yield, using such settings, solely depends on the species and the characteristics of the primary ion. In order to analyze the yield dependence on the primary ion energy, and the corresponding stopping power within the electronic excitation regime, we used a continuous electron multiplier detector to measure the primary ion current during each measurement of the mass spectra. Secondary ion yield as a function of the primary ion energy and charge is presented as well as fragmentation rates of organic molecules arginine and leu-enkephalin. Other influential instrumental drawbacks are also studied, and their effect on the results is discussed.
The work presents studies of the cationization agent effect on the ionization efficiency, and on the stability of secondary molecules, which are desorbed from the surface as a result of bombardment ...by MeV primary ions. Different organic molecule standards were mixed with various trifluoroacetate (TFA) salts, namely AgTFA, LiTFA, NaTFA and KTFA, with Ag, Li, Na and K being common cationization agents of secondary ions besides hydrogen. Results show modest differences in ionization efficiency, and significant variation of secondary ions’ stability when different cationization agents are attached to the molecule. For all reference samples, lithium provided the most stable secondary ions with almost none detected fragmentations after the desorption, while secondary ions with attached potassium were measured as much less stable, and the ratio between neutrals (fragments) and normal positive ions is estimated to be more than 0.2. However, even potassium – ionized molecules were recognized as more stable than protonated molecules.
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•Maximum secondary ion yields were measured at X-TFA/PEG 1000 concentration ratios between 1 and 10 for all X.•Na-, K- and AgTFA exhibited similar secondary ion yield increase (≈30), while the increase with LiTFA was approx. 15.•No correlation between X+ and (M + X)+ secondary ions.•Stability of secondary ions has a clear hierarchy Li > Ag > Na > K > H for all measured samples.•Larger PEG chains have longer decay times.
We report on the analysis of the onset and the intensity of metastable secondary ions, which are desorbed from the target material as a result of bombarding organic samples with MeV primary ions. The ...bimodal time-of-flight mass spectrometer, which can analyze secondary ion in linear and reflectron modes, was used for detection and characterization of such ions. The use of the bimodal mass spectrometer for this specific purpose is demonstrated on amino acid arginine, where three main fragments were detected. We have also analyzed the influence of the primary ion beam on the intensity of metastable ion signal. Results from chlorine ion beams with energies between 3 and 10 MeV have exhibited the importance of electronic sputtering on the product/precursor ion peak intensity ratio, which is significantly decreased when using primary ions with higher energy.
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•Fragmented metastable ions from MeV-SIMS can be observed as long tails of molecular peaks in mass spectra.•Quick characterization of fragments is obtained through linear mode, and more precise identification by reflectron mode.•Fragments with intensities fragment/parent >0.01 can be detected.•Higher energy primary ion beams induce less metastable secondary ions.•Fragmentation pathways are not affected by the primary ion beam energy.
The quality of molecular imaging by means of MeV primary ion-induced secondary ion mass spectrometry by coating with gold was evaluated on different reference organic molecules and plant samples. The ...enhancement of the secondary ion yield was evident for the majority of the studied analytes, reaching the highest values at gold thicknesses between 0.5 and 2 nm, and increased the intensity up to 5-fold for reference samples and >2-fold for specific peaks within the plant sample. Improved propagation of the electric field due to the target potential on otherwise electrically insulating plant samples was also evident through improved image resolution and by reducing the background in mass spectra. However, detection of several molecules was significantly decreased at even at 1 nm thick gold layer. The results indicated that an optimized sequence of analysis is required to reliably interpret results.
Human hair absorbs numerous biomolecules from the body during its growth. This can act as a fingerprint to determine substance intake of an individual, which can be useful in forensic studies. The ...cocaine concentration profile along the growth axis of hair indicates the time evolution of the metabolic incorporation of cocaine usage. It could be either assessed by chemical extraction and further analysis of hair bundels, or by direct single hair fibre analysis with mass spectroscopy imaging (MSI). Within this work, we analyzed the cocaine distribution in individual hair samples using MeV-SIMS. Unlike conventional surface analysis methods, we demonstrate high yields of nonfragmented molecular ions from the surface of biological materials, resulting in high chemical sensitivity and non-destructive characterisation. Hair samples were prepared by longitudinally cutting along the axis of growth, leaving half-cylindrical shape to access the interior structure of the hair by the probing ion beam, and attached to the silicon wafer. A focused 5.8 MeV 35Cl6+ beam was scanned across the intact, chemically pristine hair structure. A non-fragmented protonated M+ H+ cocaine molecular peak at m/z = 304 was detected and localized along the cross-section of the hair. Its intensity exhibits strong fluctuations along the direction of the hair's growth, with pronounced peaks as narrow as 50 micrometres, corresponding to a metabolic incorporation time of approx. three hours.
MeV-SIMS is an emerging mass spectrometry imaging method, which utilizes fast, heavy ions to desorb secondary molecules. High yields and low fragmentation rates of large molecules, associated with ...the electronic sputtering process, make it particularly useful in biomedical research, where insight into distribution of organic molecules is needed. Since the implementation of MeV-SIMS in to the micro-beam line at the tandem accelerator of Jožef Stefan Institute, MeV-SIMS provided some valuable observations on the distribution of biomolecules in plant tissue, as discussed by Jenčič et al. (Nucl. Inst. Methods Phys. Res. B.
371
, 205–210,
2016
; Nucl. Inst. Methods Phys. Res. B.
404
, 140–145, 2017). However, limited focusing ability of the chlorine ion beam only allowed imaging at the tissue level. In order to surpass shortcomings of the existing method, we introduced a new approach, where we employ a continuous, low-current primary beam. In this mode, we bombard thin samples with a steady chlorine ion flux of approx. 5000 ions/s. After desorbing molecules, chlorine ions penetrate through the thinly cut sample and trigger the time-of-flight “start” signal on a continuous electron multiplier detector, positioned behind the sample. Such bombardment is more effective than previously used pulsing-beam mode, which demanded several orders of magnitude higher primary ion beam currents. Sub-micrometer focusing of low-current primary ion beam allows imaging of biological tissue on a subcellular scale. Simultaneously, new time-of-flight acquisition approach also improves mass resolution by a factor of 5. Within the article, we compare the performance of both methods and demonstrate the application of continuous mode on biological tissue. We also describe the thin sample preparation protocol, necessary for measurements with low primary ion currents.
In the present work we have investigated the chemical sensitivity of a mass spectrometry imaging method MeV – SIMS. Primary ion beam within the MeV energy range domain was employed to bombard samples ...of two organic compounds; amino acid arginine, and peptide hormone angiotensin II (human), with average molecular weights of 174.2 u and 1046.2 u respectively. Secondary ion yield was measured as a function of number of molecules per area unit, and the detection limit was determined. For both molecular compounds and two different energies of primary 35Cl ion beam, the secondary ion yield exhibited a significant decrease below the area density of 1015 molecules/cm2, while the density of 1013 molecules/cm2 resulted in molecular peak / background ratio being lesser than 3, which is below the commonly used sensitivity threshold in other techniques. Other experiment related drawbacks to sensitivity were also discussed.
The present work reports on cationization characteristics of organic molecules in alkali metal environment. Samples of arginine and polyethylene glycol polymers with average masses of 600, 1000 and ...1500 were mixed with sodium- and potassium trifluoroacetate of various concentrations, and analyzed through secondary ion mass spectrometry. Bombardment proceeded with ions within both keV and MeV energy domains. Added salts positively affected the secondary ion yield through attachment of Na or K to organic molecule. Ionization differences between swift (MeV) ions and cluster ions, commonly used for secondary ion mass spectrometry analysis, were studied for arginine and PEG 600. While for arginine, secondary ion yield enhancement was only by a factor of 2, when analysing with MeV ions, and no enhancement was observed with keV Bi3 clusters, all polyethylene glycol samples showed increase of the secondary ion yield by factors between 3 and 40, depending on the amount of potassium or sodium that was mixed into the matrix. Additionally, higher amounts of salts also resulted in decreased fragmentation probability for organic molecules, reducing the intensities of specific fragments by more than two orders of magnitude.
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•Added salts significantly increase secondary ion yield for both keV and MeV primary ions.•Ionization increase due to salt addition is greater with keV SIMS.•Added matrix reduces fragmentation – more with MeV-SIMS.•With secondary ion yields of approx. 10−2, submicron molecular imaging is feasible.
Secondary ion mass spectrometry (SIMS), based on primary ions within the MeV energy domain, also known as MeV-SIMS, is a subject of increasing scientific interest. The main drive for the interest in ...the development of MeV-SIMS is the ability to desorb high yields of large non-fragmented organic molecular ions from the sample surface. This makes MeV-SIMS particulary useful in imaging of biological tissues.
Imaging methods based on scanning a focused primary ion beam are associated with demanding focusing of the heavy energetic ions. As an alternative, stigmatic imaging mode has been studied here, applying point-to-point imaging characteristics of secondary ions in the linear Time-Of-Flight mass spectrometer. In stigmatic imaging approaches, spatial resolution is independent of the focussed spot size of the ionising primary ion beam, but instead dependant on the ability of the ion optics to project an image of the ion distributions removed from the surface onto a position sensitive ion detector.
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