Chemical Imaging of Buried Interfaces in Organic-Inorganic Devices Using Focused Ion Beam-Time-of-Flight-Secondary-Ion Mass Spectrometry.

Organic-inorganic hybrid materials enable the design and fabrication of new materials with enhanced properties. The interface between the organic and inorganic materials is often critical to the device's performance; therefore, chemical characterization is of significant interest. Because the interfaces are often buried, milling by focused ion beams (FIBs) to expose the interface is becoming increasingly popular. Chemical imaging can subsequently be obtained using secondary-ion mass spectrometry (SIMS). However, the FIB milling process damages the organic material. In this study, we make an organic-inorganic test structure to develop a detailed understanding of the processes involved in FIB milling and SIMS imaging. We provide an analysis methodology that involves a "clean-up" process using sputtering with an argon gas cluster ion source to remove the FIB-induced damage. The methodology is evaluated for two additive manufactured devices, an encapsulated strain sensor containing silver tracks embedded in a polymeric material and a copper track on a flexible polymeric substrate created using a novel nanoparticle sintering technique.

The 3D OrbiSIMS-label-free metabolic imaging with subcellular lateral resolution and high mass-resolving power.

We report the development of a 3D OrbiSIMS instrument for label-free biomedical imaging. It combines the high spatial resolution of secondary ion mass spectrometry (SIMS; under 200 nm for inorganic species and under 2 µm for biomolecules) with the high mass-resolving power of an Orbitrap (>240,000 at m/z 200). This allows exogenous and endogenous metabolites to be visualized in 3D with subcellular resolution. We imaged the distribution of neurotransmitters-gamma-aminobutyric acid, dopamine and serotonin-with high spectroscopic confidence in the mouse hippocampus. We also putatively annotated and mapped the subcellular localization of 29 sulfoglycosphingolipids and 45 glycerophospholipids, and we confirmed lipid identities with tandem mass spectrometry. We demonstrated single-cell metabolomic profiling using rat alveolar macrophage cells incubated with different concentrations of the drug amiodarone, and we observed that the upregulation of phospholipid species and cholesterol is correlated with the accumulation of amiodarone.

Argon cluster ion source evaluation on lipid standards and rat brain tissue samples.

Argon cluster ion sources for sputtering and secondary ion mass spectrometry use projectiles consisting of several hundreds of atoms, accelerated to 10-20 keV, and deposit their kinetic energy within the top few nanometers of the surface. For organic materials, the sputtering yield is high removing material to similar depth. Consequently, the exposed new surface is relatively damage free. It has thus been demonstrated on model samples that it is now really possible to perform dual beam depth profiling experiments in organic materials with this new kind of ion source. Here, this possibility has been tested directly on tissue samples, 14 µm thick rat brain sections, allowing primary ion doses much larger than the so-called static secondary ion mass spectrometry (SIMS) limit and demonstrating the possibility to enhance the sensitivity of time-of-flight (TOF)-SIMS biological imaging. However, the depth analyses have also shown some variations of the chemical composition as a function of depth, particularly for cholesterol, as well as some possible matrix effects due to the presence or absence of this compound.

Spatial-resolution limits in mass spectrometry imaging of supported lipid bilayers and individual lipid vesicles.

The capabilities of time-of-flight secondary ion mass spectrometry (TOF-SIMS) with regards to limits in lateral resolution for biological samples are examined using supported lipid bilayers and individual lipid vesicles, both being among the most commonly used cell membrane mimics. Using supported 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers confined to a SiO(2) substrate by a chemically modified gold surface, the edge of the lipid bilayer was analyzed by imaging TOF-SIMS to assess the lateral resolution. The results using 80 keV Bi(3)(2+) primary ions show that, under optimized conditions, mass spectrometry imaging of specific unlabeled lipid fragments is possible with sub-100 nm lateral resolution. Comparison of the secondary ion yields for the phosphocholine ion (m/z 184) from a POPC bilayer using C(60)(+) or Bi(3)(+) primary ions showed similar results, indicating an advantage of Bi(3)(+) primary ions for high-resolution imaging of lipid membranes, due to their better demonstrated focusing capability. Moreover, using 300 nm vesicles of different lipid composition, the capability to detect and chemically identify individual submicrometer lipid vesicles at separations down to approximately 1 microm is demonstrated.

Imaging G-SIMS: a novel bismuth-manganese source emitter.

G-SIMS (gentle-SIMS) is a powerful method that considerably simplifies complex static secondary ion mass spectrometry (SSIMS) analysis of organics at surfaces. G-SIMS uses two primary ion beams that generate high and low fragmentation conditions at the surface. This allows an extrapolation to equivalent experimental conditions with very low fragmentation. Consequently, the spectra are less complex, contain more structural information and are simpler to interpret. In general, G-SIMS spectra more closely resemble electron ionisation mass spectra than SSIMS spectra. A barrier for the wider uptake of G-SIMS is the requirement for two ion beams producing suitably different fragmentation conditions and the need for their spatial registration (spatial alignment) at the surface, which is especially important for heterogeneous samples. The most popular source is the liquid metal ion source (LMIS), which is now sold with almost every new time-of-flight (TOF)-SIMS instrument. Here, we have developed a novel bismuth-manganese emitter (the 'G-tip') for the popular LMISs. This simplifies the alignment and gives excellent G-SIMS imaging and spectroscopy without significantly compromising the bismuth cluster ion beam performance.

Improvement of biological time-of-flight-secondary ion mass spectrometry imaging with a bismuth cluster ion source.

A new liquid metal ion gun (LMIG) filled with bismuth has been fitted to a time-of-flight-secondary ion mass spectrometer (TOF-SIMS). This source provides beams of Bi(n)q+ clusters with n = 1-7 and q = 1 and 2. The appropriate clusters have much better intensities and efficiencies than the Au3+ gold clusters recently used in TOF-SIMS imaging, and allow better lateral and mass resolution. The different beams delivered by this ion source have been tested for biological imaging of rat brain sections. The results show a great improvement of the imaging capabilities in terms of accessible mass range and useful lateral resolution. Secondary ion yields Y, disappearance cross sections sigma, efficiencies E = Y/sigma , and useful lateral resolutions deltaL have been compared using the different bismuth clusters, directly onto the surface of rat brain sections and for several positive and negative secondary ions with m/z ranging from 23 up to more than 750. The efficiency and the imaging capabilities of the different primary ions are compared by taking into account the primary ion current for reasonable acquisition times. The two best primary ions are Bi3+ and Bi5(2+). The Bi3+ ion beam has a current at least five times larger than Au3+ and therefore is an excellent beam for large-area imaging. Bi5(2+) ions exhibit large secondary ions yields and a reasonable intensity making them suitable for small-area images with an excellent sensitivity and a possible useful lateral resolution <400 nm.

Resonance and nonresonant laser ionization of sputtered uranium atoms from thin films and single microparticles: evaluation of a combined system for particle trace analysis.

The resonance and nonresonant laser ionization of uranium atoms sputtered from thin metal films and individual micrometer-size uranium oxide particles, respectively, was studied to evaluate a new setup for the analysis of actinide-containing micrometer-size particles. Experiments using nonresonant (193-nm) ionization of atoms and molecules sputtered from micrometer-size uranium oxide particles have shown that the uranium detection efficiencies for sputtered neutral atoms are approximately 2 orders of magnitude higher than for secondary ions. In uranium particles of 0.5-microm diameter, 6 x 10(6) atoms of 235U were easily detected and the isotopic ratio of 235U/238U = 0.0048 +/- 4.6% is in excellent agreement with the certified value. The use of two-color, two-step resonance ionization of the sputtered neutral uranium atoms from thin films was investigated. Several excitation schemes were tested, and a significant population of several low-lying metastable states after ion sputtering was observed. Autoionizing states for double-resonant ionization were determined, and the high selectivity of ionization schemes involving these autoionizing states was illustrated by comparing the flight-time distributions of different sputtered species obtained both by resonance and nonresonant multiphoton (355-nm) laser postionization. Ideally, the options for resonance as well as nonresonant ionization would be combined in a single setup, to obtain a large gain in sensitivity and selectivity. Thus, information about the main components as well as specific isotopic information of a trace element could be obtained from the same single particle.