Direct identification of interfacial degradation in blue OLEDs using nanoscale chemical depth profiling.

Understanding the degradation mechanism of organic light-emitting diodes (OLED) is essential to improve device performance and stability. OLED failure, if not process-related, arises mostly from chemical instability. However, the challenges of sampling from nanoscale organic layers and interfaces with enough analytical information has hampered identification of degradation products and mechanisms. Here, we present a high-resolution diagnostic method of OLED degradation using an Orbitrap mass spectrometer equipped with a gas cluster ion beam to gently desorb nanometre levels of materials, providing unambiguous molecular information with 7-nm depth resolution. We chemically depth profile and analyse blue phosphorescent and thermally-activated delayed fluorescent (TADF) OLED devices at different degradation levels. For OLED devices with short operational lifetimes, dominant chemical degradation mainly relate to oxygen loss of molecules that occur at the interface between emission and electron transport layers (EML/ETL) where exciton distribution is maximised, confirmed by emission zone measurements. We also show approximately one order of magnitude increase in lifetime of devices with slightly modified host materials, which present minimal EML/ETL interfacial degradation and show the method can provide insight for future material and device architecture development.

Multimodal imaging of drug and excipients in rat lungs following an inhaled administration of controlled-release drug laden PLGA microparticles.

Controlled-release formulations, in the form of micro- or nanoparticles, are increasingly attractive to the pharmaceutical industry for drug delivery. For respiratory illnesses, controlled-release microparticle formulations provide an opportunity to deliver a higher percentage of an inhaled medicament dose to the lung, thus potentially reducing the therapeutic dose, frequency of dosing, and minimising side-effects. We describe the use of a multimodal approach consisting of MALDI MS imaging, 3D depth profiling TOF-SIMS analysis, and histopathology to monitor the distribution of drug and excipients in sections taken from excised rat lungs following an inhaled administration of drug-laden microparticles. Following a single dose, the administered drug was detected in the lung via both MALDI MS and TOF-SIMS over a range of time points. Both imaging techniques enabled the characterisation of the distribution and retention of drug particles and identified differences in the capabilities of both imaging modalities. Histochemical staining of consecutive sections was used to provide biological context to the findings and will also be discussed in this presentation. We demonstrate how this multimodal approach could be used to help increase our understanding of the use of controlled release microparticles.

Correlative Hyperspectral Imaging Using a Dimensionality-Reduction-Based Image Fusion Method.

Chemical imaging techniques are increasingly being used in combination to achieve a greater understanding of a sample. This is especially true in the case of mass spectrometry imaging (MSI), where the use of different ionization sources allows detection of different classes of molecules across a range of spatial resolutions. There has been significant recent effort in the development of data fusion algorithms that attempt to combine the benefits of multiple techniques, such that the output provides additional information that would have not been present or obvious from the individual techniques alone. However, the majority of the data fusion methods currently in use rely on image registration to generate the fused data and therefore can suffer from artifacts caused by interpolation. Here, we present a method for data fusion that does not incorporate interpolation-based artifacts into the final fused data, applied to data acquired from multiple chemical imaging modalities. The method is evaluated using simulated data and a model polymer blend sample, before being applied to biological samples of mouse brain and lung.

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.

Intracellular Drug Uptake-A Comparison of Single Cell Measurements Using ToF-SIMS Imaging and Quantification from Cell Populations with LC/MS/MS.

ToF-SIMS is a label-free imaging method that has been shown to enable imaging of amiodarone in single rat macrophage (NR8383) cells. In this study, we show that the method extends to three other cell lines relevant to drug discovery: human embryonic kidney (HEK293), cervical cancer (HeLa), and liver cancer (HepG2). There is significant interest in the variation of drug uptake at the single cell level, and we use ToF-SIMS to show that there is great diversity between individual cells and when comparing each of the cell types. These single cell measurements are compared to quantitative measurements of cell-associated amiodarone for the population using LC/MS/MS and cell counting with flow cytometry. NR8383 and HepG2 cells uptake the greatest amount of amiodarone with an average of 2.38 and 2.60 pg per cell, respectively, and HeLa and Hek 293 have a significantly lower amount of amiodarone at 0.43 and 0.36 pg per cell, respectively. The amount of cell-associated drug for the ensemble population measurement (LC/MS/MS) is compared with the ToF-SIMS single cell data: a similar amount of drug was detected per cell for the NR8383, and HepG2 cells at a greater level than that for the HEK293 cells. However, the two techniques did not agree for the HeLa cells, and we postulate potential reasons for this.

Embedding-Free Method for Preparation of Cross-Sections of Organic Materials for Micro Chemical Analysis Using Gas Cluster Ion Beam Sputtering.

We present a novel in situ mask method for the preparation of cross-sections of organic materials such as polymer multilayer films suitable for chemical imaging of buried interfaces. We demonstrate this method on a model buried interface system consisting of a piece of Scotch tape adhered to a PET substrate and a protective film used in consumer packaging. A high dose of gallium from a focused ion beam (FIB) was used to produce a damaged overlayer on the surface of the organic sample. The damaged layer has a significantly slower sputter rate compared to the native undamaged organic material. Therefore, during gas cluster ion beam (GCIB) depth profiling experiments the damaged layer functions as a mask, protecting the sample beneath and producing a cross-section at the edge of the mask. The FIB itself cannot be used directly to prepare the cross-section since the organic materials are easily damaged. A four step workflow is described including a final cleaning procedure to remove redeposited material from the cross-section. The workflow is completed in a few hours for samples up to 100 µm thickness. The method does not require sample embedding and is suited to automated analysis, which can be important benefits for industrial analysis where a variety of samples are analyzed routinely.

Semiempirical Rules To Determine Drug Sensitivity and Ionization Efficiency in Secondary Ion Mass Spectrometry Using a Model Tissue Sample.

There is an increasing need in the pharmaceutical industry to reduce drug failure at late stage and thus reduce the cost of developing a new medicine. Since most drug targets are intracellular, this requires a better understanding of the drug disposition within a cell. Secondary ion mass spectrometry has been identified as a potentially important technique to do this, as it is label-free and allows imaging in 3D with subcellular resolution and recent studies have shown promise for amiodarone. An important analytical parameter is sensitivity, and we measure this in a bovine liver homogenate reference sample for 20 drugs representing important class types relevant to the pharmaceutical industry. We also measure the sensitivity for pure drug and show, for the first time, that the secondary ion mass spectrometry (SIMS) positive ionization efficiency for small molecules is a simple power-law relationship to the log P value. This discovery will be important for advancing the understanding of the SIMS ionization process in small molecules that has, until now, been elusive. This simple relationship is found to hold true for drug doped in the bovine liver homogenate reference sample, except for fluticasone, nicardipine, and sorafenib which suffer from severe matrix suppression. This relationship provides a simple semiempirical method to determine drug sensitivity for positive secondary ions. Furthermore, we show, on chosen models, how the use of different solvents during sample preparation can affect the ionization of analytes.

Systematic Temperature Effects in the Argon Cluster Ion Sputter Depth Profiling of Organic Materials Using Secondary Ion Mass Spectrometry.

A study is presented of the effects of sample temperature on the sputter depth profiling of two organic materials, NPB (N,N'-Di(1-naphthyl)-N,N'-diphenyl-(1,1'-biphenyl)-4,4'-diamine) and Irganox 1010, using a 5 keV Ar2000 (+) cluster ion beam and analysis by secondary ion mass spectrometry. It is shown that at low temperatures, the yields increase slowly with temperature in accordance with the Universal Sputtering Yield equation where the energy term is now modified by Trouton's rule. This occurs up to a transition temperature, T T, which is, in turn, approximately 0.8T M, where T M is the sample melting temperature in Kelvin. For NPB and Irganox 1010, these transition temperatures are close to 15 °C and 0 °C, respectively. Above this temperature, the rate of increase of the sputtering yield rises by an order of magnitude. During sputtering, the depth resolution also changes with temperature with a very small change occurring below T T. At higher temperatures, the depth resolution improves but then rapidly degrades, possibly as a result first of local crater surface diffusion and then of bulk inter-diffusion. The secondary ion spectra also change with temperature with the intensities of the molecular entities increasing least. This agrees with a model in which the molecular entities arise near the crater rim. It is recommended that for consistent results, measurements for organic materials are always made at temperatures significantly below T T or 0.8 T M, and this is generally below room temperature. Graphical Abstract ᅟ.

Peptide Fragmentation and Surface Structural Analysis by Means of ToF-SIMS Using Large Cluster Ion Sources.

Peptide or protein structural analysis is crucial for the evaluation of biochips and biodevices, therefore an analytical technique with the ability to detect and identify protein and peptide species directly from surfaces with high lateral resolution is required. In this report, the efficacy of ToF-SIMS to analyze and identify proteins directly from surfaces is evaluated. Although the physics governing the SIMS bombardment process precludes the ability for researchers to detect intact protein or larger peptides of greater than a few thousand mass unit directly, it is possible to obtain information on the partial structures of peptides or proteins using low energy per atom argon cluster ion beams. Large cluster ion beams, such as Ar clusters and C60 ion beams, produce spectra similar to those generated by tandem MS. The SIMS bombardment process also produces peptide fragment ions not detected by conventional MS/MS techniques. In order to clarify appropriate measurement conditions for peptide structural analysis, peptide fragmentation dependency on the energy of a primary ion beam and ToF-SIMS specific fragment ions are evaluated. It was found that the energy range approximately 6 ≤ E/n ≤ 10 eV/atom is most effective for peptide analysis based on peptide fragments and [M + H] ions. We also observed the cleaving of side chain moieties at extremely low-energy E/n ≤ 4 eV/atom.

Measuring Compositions in Organic Depth Profiling: Results from a VAMAS Interlaboratory Study.

We report the results of a VAMAS (Versailles Project on Advanced Materials and Standards) interlaboratory study on the measurement of composition in organic depth profiling. Layered samples with known binary compositions of Irganox 1010 and either Irganox 1098 or Fmoc-pentafluoro-l-phenylalanine in each layer were manufactured in a single batch and distributed to more than 20 participating laboratories. The samples were analyzed using argon cluster ion sputtering and either X-ray photoelectron spectroscopy (XPS) or time-of-flight secondary ion mass spectrometry (ToF-SIMS) to generate depth profiles. Participants were asked to estimate the volume fractions in two of the layers and were provided with the compositions of all other layers. Participants using XPS provided volume fractions within 0.03 of the nominal values. Participants using ToF-SIMS either made no attempt, or used various methods that gave results ranging in error from 0.02 to over 0.10 in volume fraction, the latter representing a 50% relative error for a nominal volume fraction of 0.2. Error was predominantly caused by inadequacy in the ability to compensate for primary ion intensity variations and the matrix effect in SIMS. Matrix effects in these materials appear to be more pronounced as the number of atoms in both the primary analytical ion and the secondary ion increase. Using the participants' data we show that organic SIMS matrix effects can be measured and are remarkably consistent between instruments. We provide recommendations for identifying and compensating for matrix effects. Finally, we demonstrate, using a simple normalization method, that virtually all ToF-SIMS participants could have obtained estimates of volume fraction that were at least as accurate and consistent as XPS.

3D ToF-SIMS imaging of polymer multilayer films using argon cluster sputter depth profiling.

ToF-SIMS imaging with argon cluster sputter depth profiling has provided detailed insight into the three-dimensional (3D) chemical composition of a series of polymer multilayer structures. Depths of more than 15 µm were profiled in these samples while maintaining uniform sputter rates. The 3D chemical images provide information regarding the structure of the multilayer systems that could be used to inform future systems manufacturing and development. This also includes measuring the layer homogeneity, thickness, and interface widths. The systems analyzed were spin-cast multilayers comprising alternating polystyrene (PS) and polyvinylpyrrolidone (PVP) layers. These included samples where the PVP and PS layer thickness values were kept constant throughout and samples where the layer thickness was varied as a function of depth in the multilayer. The depth profile data obtained was observed to be superior to that obtained for the same materials using alternative ion sources such as C60(n+). The data closely reflected the "as manufactured" sample specification, exhibiting good agreement with ellipsometry measurements of layer thickness, while also maintaining secondary ion intensities throughout the profiling regime. The unprecedented quality of the data allowed a detailed analysis of the chemical structure of these systems, revealing some minor imperfections within the polymer layers and demonstrating the enhanced capabilities of the argon cluster depth profiling technique.

Electron flood gun damage effects in 3D secondary ion mass spectrometry imaging of organics.

Electron flood guns used for charge compensation in secondary ion mass spectrometry (SIMS) cause chemical degradation. In this study, the effect of electron flood gun damage on argon cluster depth profiling is evaluated for poly(vinylcarbazole), 1,4-bis((1-naphthylphenyl)amino)biphenyl and Irganox 3114. Thin films of these three materials are irradiated with a range of doses from a focused beam of 20 eV electrons used for charge neutralization. SIMS chemical images of the irradiated surfaces show an ellipsoidal damaged area, approximately 3 mm in length, created by the electron beam. In depth profiles obtained with 5 keV Ar(2000)(+) sputtering from the vicinity of the damaged area, the characteristic ion signal intensity rises from a low level to a steady state. For the damaged thin films, the ion dose required to sputter through the thin film to the substrate is higher than for undamaged areas. It is shown that a damaged layer is formed and this has a sputtering yield that is reduced by up to an order of magnitude and that the thickness of the damaged layer, which increases with the electron dose, can be as much as 20 nm for Irganox 3114. The study emphasizes the importance of minimizing the neutralizing electron dose prior to the analysis.

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.

Argon cluster ion beams for organic depth profiling: results from a VAMAS interlaboratory study.

The depth profiling of organic materials with argon cluster ion sputtering has recently become widely available with several manufacturers of surface analytical instrumentation producing sources suitable for surface analysis. In this work, we assess the performance of argon cluster sources in an interlaboratory study under the auspices of VAMAS (Versailles Project on Advanced Materials and Standards). The results are compared to a previous study that focused on C(60)(q+) cluster sources using similar reference materials. Four laboratories participated using time-of-flight secondary-ion mass spectrometry for analysis, three of them using argon cluster sputtering sources and one using a C(60)(+) cluster source. The samples used for the study were organic multilayer reference materials consisting of a ∼400-nm-thick Irganox 1010 matrix with ∼1 nm marker layers of Irganox 3114 at depths of ∼50, 100, 200, and 300 nm. In accordance with a previous report, argon cluster sputtering is shown to provide effectively constant sputtering yields through these reference materials. The work additionally demonstrates that molecular secondary ions may be used to monitor the depth profile and depth resolutions approaching a full width at half maximum (fwhm) of 5 nm can be achieved. The participants employed energies of 2.5 and 5 keV for the argon clusters, and both the sputtering yields and depth resolutions are similar to those extrapolated from C(60)(+) cluster sputtering data. In contrast to C(60)(+) cluster sputtering, however, a negligible variation in sputtering yield with depth was observed and the repeatability of the sputtering yields obtained by two participants was better than 1%. We observe that, with argon cluster sputtering, the position of the marker layers may change by up to 3 nm, depending on which secondary ion is used to monitor the material in these layers, which is an effect not previously visible with C(60)(+) cluster sputtering. We also note that electron irradiation, used for charge compensation, can induce molecular damage to areas of the reference samples well beyond the analyzed region that significantly affects molecular secondary-ion intensities in the initial stages of a depth profile in these materials.

Direct electrospinning of Ag/polyvinylpyrrolidone nanocables.

Core-sheath silver nanowire/polyvinylpyrrolidone (AgNW/PVP) nanocables have been fabricated via an efficient single-spinneret electrospinning method. The core-sheath structure is revealed by combining several characterization methods. A possible formation mechanism of the AgNW/PVP nanocable involving a strong stretching during the electrospinning process is proposed. Further, electrical measurements were performed on AgNW/PVP nanocables as well as bare AgNWs, which indicated the nanocables became insulating due to the isolation of highly conductive AgNWs by insulating PVP sheath. Therefore, the described fabrication method holds potential for the fabrication of low-cost metal/polymer composite materials for nanoelectronic applications in general.

Functional electrospun polystyrene nanofibers incorporating α-, ß-, and γ-cyclodextrins: comparison of molecular filter performance.

Electrospinning has been used to successfully create polystyrene (PS) nanofibers containing either of three different types of cyclodextrin (CD); α-CD, ß-CD, and γ-CD. These three CDs are chosen because they have different sized cavities that potentially allow for selective inclusion complex (IC) formation with molecules of different size or differences in affinity of IC formation with one type of molecule. The CD containing electrospun PS nanofibers (PS/CD) were initially characterized by scanning electron microscopy (SEM) to determine the uniformity of the fibers and their fiber diameter distributions. X-ray photoelectron spectroscopy (XPS) was used to quantitatively determine the concentration of each CD on the different fiber surfaces. Static time-of-flight secondary ion mass spectrometry (static-ToF-SIMS) showed the presence of each type of CD on the PS nanofibers by the detection of both the CD sodium adduct molecular ions (M + Na+) and lower molecular weight oxygen containing fragment ions. The comparative efficiency of the PS/CD nanofibers/nanoweb for removing phenolphthalein, a model organic compound, from solution was determined by UV-vis spectrometry, and the kinetics of phenolphthalein capture was shown to follow the trend PS/α-CD > PS/ß-CD > PS/γ-CD. Direct pyrolysis mass spectrometry (DP-MS) was also performed to ascertain the relative binding strengths of the phenolphthalein for the CD cavities, and the results showed the trend in the interaction strength was ß-CD > γ-CD > α-CD. Our results demonstrate that nanofibers produced by electrospinning that incorporate cyclodextrins with different sized cavities can indeed filter organic molecules and can potentially be used for filtration, purification, and/or separation processes.

The formation and characterization of cyclodextrin functionalized polystyrene nanofibers produced by electrospinning.

Polystyrene (PS) nanofibers containing the inclusion complex forming beta-cyclodextrin (beta-CD) were successfully produced by electrospinning aimed at developing functional fibrous nanowebs. By optimization of the electrospinning parameters, which included varying the relative concentration of PS and beta-CD in the solutions, bead-free fibers were produced. Homogeneous solutions of beta-CD and PS in dimethylformamide (DMF) were used with concentrations of PS varying from 10% to 25% (w/v, with respect to DMF), and beta-CD concentrations of 1% to 50% (w/w, with respect to PS). The presence of beta-CD facilitated the production of bead-free PS fibers even from lower polymer concentrations as a result of the higher conductivity of the PS/CD solutions. The morphology and the production of bead-free PS/CD fibers were highly dependent on the beta-CD contents. Transmission electron microscope (TEM) and atomic force microscope (AFM) images showed that incorporation of beta-CD yielded PS fibers with rougher surfaces. Thermogravimetric analysis (TGA) and direct insertion probe pyrolysis mass spectroscopy (DP-MS) results confirmed the presence of beta-CD in the PS fibers. X-ray diffraction (XRD) spectra of the fibers indicated that the beta-CD molecules are distributed within the PS matrix without any phase separated crystalline aggregates up to 40% (w/w) beta-CD loading. Furthermore, chemical analyses by Fourier transform infrared (FTIR) spectroscopy studies confirm that beta-CD molecules are located within the PS fiber matrix. Finally, preliminary investigations using x-ray photoelectron spectroscopy (XPS) and time-of-flight static secondary ion mass spectrometry (ToF-static-SIMS) show the presence of the cyclodextrin molecules in the outer molecular layers of the fiber surfaces. The XPS and ToF-SIMS findings indicate that cyclodextrin functionalized PS webs would have the potential to be used as molecular filters and/or nanofilters for the purposes of filtration/purification/separation owing to surface associated beta-CD molecules which have inclusion complexation capability.