Christine M. Mahoney

Cluster secondary ion mass spectrometry of polymers and related materials.

Cluster secondary ion mass spectrometry (cluster SIMS) has played a critical role in the characterization of polymeric materials over the last decade, allowing for the ability to obtain spatially resolved surface and in-depth molecular information from many polymer systems. With the advent of new molecular sources such as C(60)(+), Au(3)(+), SF(5)(+), and Bi(3)(+), there are considerable increases in secondary ion signal as compared to more conventional atomic beams (Ar(+), Cs(+), or Ga(+)). In addition, compositional depth profiling in organic and polymeric systems is now feasible, without the rapid signal decay that is typically observed under atomic bombardment. The premise behind the success of cluster SIMS is that compared to atomic beams, polyatomic beams tend to cause surface-localized damage with rapid sputter removal rates, resulting in a system at equilibrium, where the damage created is rapidly removed before it can accumulate. Though this may be partly true, there are actually much more complex chemistries occurring under polyatomic bombardment of organic and polymeric materials, which need to be considered and discussed to better understand and define the important parameters for successful depth profiling. The following presents a review of the current literature on polymer analysis using cluster beams. This review will focus on the surface and in-depth characterization of polymer samples with cluster sources, but will also discuss the characterization of other relevant organic materials, and basic polymer radiation chemistry.

Three-dimensional time-of-flight secondary ion mass spectrometry imaging of a pharmaceutical in a coronary stent coating as a function of elution time.

Three-dimensional (3D) chemical images reveal the surface and subsurface distribution of pharmaceutical molecules in a coronary stent coating and are used to visualize the drug distribution as a function of elution time. The coronary stent coating consists of 25% (w/w) sirolimus in a poly(lactic-co-glycolic acid) (PLGA) matrix and is spray-coated onto metal coupons. Information regarding the 3D distribution of sirolimus in PLGA as a function of elution time was obtained by time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging using a Au(+) ion beam for analysis in conjunction with a C(60)(+) ion beam for sputter depth profiling. The examined formulation is shown to have large areas of the surface as well as subsurface channels that are composed primarily of the drug, followed by a drug-depleted region, and finally, a relatively homogeneous dispersion of the drug in the polymer matrix. Elution is shown to occur from the drug-enriched surface region on a relatively short time scale and more gradually from the subsurface regions of homogeneously dispersed drug. Bulk composition was also probed by X-ray photoelectron spectroscopy (XPS) depth profiling and confocal Raman imaging, the results of which substantiate the TOF-SIMS 3D images. Finally, the effectiveness of a C(60)(+) ion beam for use in 3D characterization of organic systems is demonstrated against another polyatomic ion source (e.g., SF(5)(+)).

Three-Dimensional Compositional Analysis of Drug Eluting Stent Coatings Using Cluster Secondary Ion Mass Spectrometry

Cluster secondary ion mass spectrometry (cluster SIMS) employing an SF5+ polyatomic primary ion sputter source in conjunction with a Bi3+ analysis source was used to obtain three-dimensional molecular information in polymeric-based drug-eluting stent coatings. The formulations of the coatings varied from 0% to 50% (w/w) sirolimus drug in poly(lactic-co-glycolic acid) and were prepared on both MP35N metal alloy coupons and bare metal stents. All cluster SIMS depth profiles obtained indicated a drug-enriched surface region, followed by a drug-depletion region, and finally a constant bulk composition region, similar to previous data obtained in polymeric blend systems. The drug overlayer thickness was determined to increase with increasing sirolimus content. Sample temperature was determined to play an important role in the resulting depth profiles, where it was shown that the best profiles were obtained at low temperatures (-100 degrees C). At these temperatures, molecular signals typically remained constant through the entire depth of the film (approximately 6.5 microm) in some cases, as opposed to the typical 1 microm-2 microm depth limit, which is achievable at room temperature. The 3-D imaging capabilities of cluster SIMS were successfully demonstrated and indicated a significant amount of subsurface domain formation in the 25% and 50% sirolimus samples, but not in the 5% sample, which was homogeneous. These results clearly illustrate the utility of cluster SIMS for probing the 3-D structure in polymeric-based drug delivery devices.

Microstructure and Elution of Tetracycline from Block Copolymer Coatings

A critical metrology issue for pharmaceutical industries is the application of analytical techniques for the characterization of drug delivery systems to address interrelationships between processing, structure, and drug release. In this study, cast coatings were formed from solutions of poly(styrene-b-isobutylene-b-styrene) (SIBS) and tetracycline in tetrahydrofuran (THF). These coatings were characterized by several imaging modalities, including time-of-flight secondary ion mass spectrometry (TOF-SIMS) for chemical imaging and analysis, atomic force microscopy (AFM) for determination of surface structure and morphology, and laser scanning confocal microscopy (LSCM), which was used to characterize the three-dimensional structure beneath the surface. The results showed phase separation between the drug and copolymer regions. The size of the tetracycline phase in the polymer matrix ranged from hundreds of nanometers to tens of microns, depending on coating composition. The mass of drug released was not found to be proportional to drug loading, because the size and spatial distribution of the drug phase varied with drug loading and solvent evaporation rate, which in turn affected the amount of drug released.

Characterization of Composition C4 Explosives using Time-of-Flight Secondary Ion Mass Spectrometry and X-ray Photoelectron Spectroscopy

The application of surface analytical techniques such as time-of-flight secondary ion mass spectrometry (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS) is explored as a means of differentiating between composition C4 plastic explosives (C-4). Three different C-4 samples including U.S. military grade C-4, commercial C-4 (also from the United States), and C-4 from England (PE-4) were obtained and analyzed using both ToF-SIMS and XPS. ToF-SIMS was able to successfully discriminate between different C-4 samples with the aid of principal component analysis, a multivariate statistical analysis approach often used to reduce the dimensionality of complex data. ToF-SIMS imaging was also used to obtain information about the spatial distribution of the various additives contained within the samples. The results indicated that the samples could potentially be characterized by their 2-D chemical and morphological structure, which varied from sample to sample. XPS analysis also showed significant variation between samples, with changes in the atomic concentrations, as well as changes in the shapes of the high-resolution C 1s and O 1s spectra. These results clearly demonstrate the feasibility of utilizing both ToF-SIMS and XPS as tools for the direct characterization and differentiation of C-4 samples for forensic applications.

Phase separation at the surface of poly(ethylene oxide)-containing biodegradable poly(L-lactic acid) blends.

The surface chemistry and in-depth distribution of the composition of a poly(ethylene oxide) (PEO)-containing biodegradable poly(L-lactic acid) (PLLA) blend matrix system have been investigated using X-ray photoelectron spectroscopy (XPS). This study reports detailed quantitative compositional information using a novel numerical method for determining depth profiles. The PEO system studied is an amphiphilic Pluronic P104 surfactant, PEO-b-poly(propylene oxide) (PPO)-b-PEO. The extent of phase separation is analyzed by determining the surface enrichment of the PEO component via measurement of chemical composition at the polymer-air interface. For this blend system, the combination of the PPO component in the Pluronic surfactants drives the formation of a surface excess of Pluronic in the blends with PLLA. The surface excess profile shows a rapid increase in Pluronic surface composition versus bulk Pluronic mass fractions of 1-5%, but the profile levels off above bulk Pluronic mass fractions of 5%.

Bayesian Integration and Classification of Composition C-4 Plastic Explosives Based on Time-of-Flight-Secondary Ion Mass Spectrometry and Laser Ablation-Inductively Coupled Plasma Mass Spectrometry

Time-of-flight-secondary ion mass spectrometry (TOF-SIMS) and laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS) were used for characterization and identification of unique signatures from a series of 18 Composition C-4 plastic explosives. The samples were obtained from various commercial and military sources around the country. Positive and negative ion TOF-SIMS data were acquired directly from the C-4 residue on Si surfaces, where the positive ion mass spectra obtained were consistent with the major composition of organic additives, and the negative ion mass spectra were more consistent with explosive content in the C-4 samples. Each series of mass spectra was subjected to partial least squares-discriminant analysis (PLS-DA), a multivariate statistical analysis approach which serves to first find the areas of maximum variance within different classes of C-4 and subsequently to classify unknown samples based on correlations between the unknown data set and the original data set (often referred to as a training data set). This method was able to successfully classify test samples of C-4, though with a limited degree of certainty. The classification accuracy of the method was further improved by integrating the positive and negative ion data using a Bayesian approach. The TOF-SIMS data was combined with a second analytical method, LA-ICPMS, which was used to analyze elemental signatures in the C-4. The integrated data were able to classify test samples with a high degree of certainty. Results indicate that this Bayesian integrated approach constitutes a robust classification method that should be employable even in dirty samples collected in the field.

Forensics Applications of Secondary Ion Mass Spectrometry

Our government is always in need of precise tools that can rapidly and accurately characterize explosive compositions. At the Environmental Molecular Sciences Laboratory (EMSL) at PNNL, we have stateof-the-art facilities containing a unique suite of analytical tools: some of which are not located anywhere else in the world. Developing these facilities and tools for national security interests will help our government both prevent, and respond to terrorist acts in a timely manner.

3-D Characterization of Biomaterials with Cluster SIMS

Secondary Ion Mass Spectrometry (SIMS) has proven to be a useful tool in the analysis of biomaterials and drug delivery systems. With SIMS, the distribution of components in biomaterials systems can potentially be determined with a high degree of spatial resolution (<1 μm) and sensitivity (as low as ppm (μg / g)) when compared to other analytical methods such as Raman and IR spectroscopies [1]. Unfortunately, the widespread use of SIMS for imaging and depth profiling of organic constituents in drug delivery systems has been severely limited by low secondary ion yields and beam-induced damage effects that result from the use of monatomic primary ion beams, resulting in low sensitivity and precluding compositional depth profiling. One potential solution to this limitation is to use cluster or polyatomic primary ion bombardment. Cluster primary ion sources (such as SF5 and C60) have already generated considerable interest for organic SIMS analysis, where they have resulted in significant improvements (up to 1000 fold) in characteristic molecular secondary ion yields and in some cases have resulted in decreased beam-induced damage [2,3,4]. This decreased beam-induced damage coupled with an increased sputter rate has led to the ability to depth profile through some organic and polymeric materials without the characteristic rapid signal decay observed with monatomic primary ion sources [2,4].