Scott R. Bryan

A microcomputer based digital imaging system for ion microanalysis

A microcomputer based digital imaging system was developed for a Cameca IMS‐3f ion microscope permitting real‐time digital acquisition of secondary ion images. Image signal‐to‐noise enhancement results from random noise reduction by real‐time ensemble averaging and from a reduction of pattern noise in the charge injection device (CID) array by subtraction of blank frames. Acquired images comprise 244times248 pixel arrays with 8‐bit intensity resolution. Images are displayed on a colour monitor in a grey scale or pseudo‐colour using one of four programmable lookup tables. Image processing software permits off‐line ion image enhancement and manipulation as well as multitechnique digital image correlations. System capability is illustrated by a biological example involving digital imaging studies of Al distribution in osteomalacic bone tissue, including correlative light microscopy and ion microanalysis.

A New Method and Mass Spectrometer Design for TOF-SIMS Parallel Imaging MS/MS

We report a method for the unambiguous identification of molecules in biological and materials specimens at high practical lateral resolution using a new TOF-SIMS parallel imaging MS/MS spectrometer. The tandem mass spectrometry imaging reported here is based on the precise monoisotopic selection of precursor ions from a TOF-SIMS secondary ion stream followed by the parallel and synchronous collection of the product ion data. Thus, our new method enables simultaneous surface screening of a complex matrix chemistry with TOF-SIMS (MS(1)) imaging and targeted identification of matrix components with MS/MS (MS(2)) imaging. This approach takes optimal advantage of all ions produced from a multicomponent sample, compared to classical tandem mass spectrometric methods that discard all ions with the exception of specific ions of interest. We have applied this approach for molecular surface analysis and molecular identification on the nanometer scale. High abundance sensitivity is achieved at low primary ion dose density; therefore, one-of-a-kind samples may be relentlessly probed before ion-beam-induced molecular damage is observed.

Parallel imaging MS/MS TOF-SIMS instrument

The authors have developed a parallel imaging MS/MS capability for the PHI nanoTOF II time-of-flight secondary ion mass spectrometry (TOF-SIMS) instrument. The unique design allows a 1 Da wide precursor mass window to be extracted from a stream of mass separated secondary ions while all other secondary ions are detected in the normal manner at the standard TOF-SIMS detector. The selected precursor ions are deflected into an activation cell where they are fragmented using high energy collision induced dissociation and mass analyzed in a separate linear TOF mass spectrometer. This TOF-TOF approach allows MS/MS to be accomplished at a high speed maintaining the primary ion beam repetition rates used in TOF-SIMS. The new MS/MS capability enables molecular identification to be extended to higher mass ions where the mass accuracy of TOF-SIMS is not sufficient to unambiguously identify molecular structure. The ability to acquire TOF-SIMS and MS/MS data simultaneously from the identical analytical volume is a pow...

The Composition of Poly(Ethylene Terephthalate) (PET) Surface Precipitates Determined at High Resolving Power by Tandem Mass Spectrometry Imaging

We present the first demonstration of a general method for the chemical characterization of small surface features at high magnification via simultaneous collection of mass spectrometry (MS) imaging and tandem MS imaging data. High lateral resolution tandem secondary ion MS imaging is employed to determine the composition of surface features on poly(ethylene terephthalate) (PET) that precipitate during heat treatment. The surface features, probed at a lateral resolving power of<200 nm using a surface-sensitive ion beam, are found to be comprised of ethylene terephthalate trimer at a greater abundance than is observed in the surrounding polymer matrix. This is the first chemical identification of PET surface precipitates made without either an extraction step or the use of a reference material. The new capability employed for this study achieves the highest practical lateral resolution ever reported for tandem MS imaging.

Sub-Micron Resolution Imaging with Bio-Molecular Identification by TOF-SIMS Parallel Imaging MS/MS

TOF-SIMS offers a number of advantages which include high spatial resolution, high abundance sensitivity, and shallow sampling depth. But, TOF-SIMS has had no means for unambiguous molecular identification and this inherent weakness in high m/z molecular identification has greatly impeded its adoption into fields of biological research. MALDI is routinely used for molecular identification via tandem MS but has been limited to a practical lateral resolution of greater than 10 μm. Data reproducibility has been problematic with MALDI due largely to variations of the applied matrix, and a sample is consumed in a single multiplexed analysis. The deficiencies of both TOF-SIMS and MALDI drive an enormous analytical need in biological research because many disease states and therapeutics must be understood at the cellular or sub-cellular scale.

A Revolutionary Approach for Molecular Imaging with TOF-SIMS Parallel Imaging MS/MS

At the time of introduction in the 1980’s, TOF-SIMS was a surface analysis research instrument providing elemental ion and limited molecular fragment ion spectra and images of the outer layer of solid materials. Since the initial successes, TOF-SIMS has evolved into a more powerful technique based on several important instrumentation advances. These advances, listed in chronological order, are listed below:  Improved mass resolution up to 16,000 m/Δm  Improved depth of field up to 200 μm for analysis of many real world samples  Enhanced higher mass fragment ion sensitivity using cluster ion probe beams, i.e. Bin  Organic depth profiling, with minimal chemical damage, using cluster ion sputter sources o SF6 o Glycerol o C60 o Coronene o Arn Gas Cluster Ion Beam (GCIB)  3D Imaging, FIB-TOF and 3D Tomography All of these advances have expanded the breadth of applications, most notably the use of TOF-SIMS for analyzing organic contamination, tissue cross sections and polymer surfaces with sub-micron spatial resolution. The limitation of organic molecular fragment compositional peak assignments, based on the mass resolution up to 16,000 m/Δm and the mass accuracy of ~10 to 20 ppm for current state-of-the-art TOF analyzers, has obviated some of the benefits of the listed advancements. Routine analysis can produce ion spectra and ion images over 2,000 m/z. For many molecular ion fragments, unambiguous peak assignments cannot be achieved over a mass of ~ 200 m/z (for either positive or negative polarity ions). Clearly a paradigm shift is needed in the data acquisition of higher mass molecular ion fragments for TOF-SIMS to reach its potential for sub-micron spatial resolution analyses. This is particularly important for cellular and sub-cellular biological tissue analysis, as well as micro-features on polymers, biomaterials, and other organic materials.

Dynamic Range Consideration for Digital Secondary Ion Image Depth Profiling

Digital imaging systems, capable of on-line acquisition of digital image depth profiles (IDP) using ion microscopes [1–3] and ion microprobes [4], have fostered the recent development of SIMS for 3-dimensional analysis. The series of digital images which result from.an IDP may represent several thousand individual small area depth profiles acquired in parallel. A local area depth profile (LADP) may be generated from any selected area within the image field by simply summing the intensities of pixels within the selected area for each image of the IDP [5–7]. The main disadvantage of image depth profiling with a direct imaging ion microscope (Cameca IMS-3F), however, has been dynamic range limitations. As a result of the high speed of data acquisition required for real-time (30 frames/s) digital imaging, many framebuffers are only 8-bits deep. Therefore, under a given acquisition time and microchannel plate gain, the intensity of any given pixel can only vary from 0 to 255 over the course of the IDP.

Correction Method for Ion Yield Transients in the Near Surface Region of Sims Depth Profiles

As solid state device features continue to decrease in size, it has become more important to characterize dopant concentrations within the first several hundred angstroms of the surface. Secondary ion mass spectrometry (SIMS) is the technique of choice for dopant depth profiling due to its high sensitivity and good depth resolution. In order to increase the sensitivity of SIMS, electropositive elements (e.g. oxygen) or electronegative elements (e.g. cesium) are used as primary ion species to enhance positive or negative secondary ion yields, respectively. This has the disadvantage, however, of causing secondary ion yields to vary by up to several orders of magnitude over the first few hundred angstroms of a depth profile as the implanted primary ion concentration increases [1,2]. Secondary ion yields stabilize once the primary ion reaches a steady state concentration, which occurs at a depth proportional to the range of the primary ions in the solid. This ion yield transient artifact hinders quantification of dopant concentrations until the primary ion concentration reaches steady state.