Blistering Mechanism Research Articles

A unified mathematical modelling and simulation for cathodic blistering mechanism incorporating diffusion and fracture mechanics concepts

A novel mathematical model has been developed to understand the mechanism of blister initiation and propagation. The model employs a two-part theoretical approach encompassing the debondment of a coating film from the substrate, coupled with the design components incorporating diffusion and fracture mechanics, where the latter is derived from equi-biaxial tensile loading. Integrating the two components, a comprehensive mathematical design for the propagation of blister boundaries based on specific toughness functions and mode adjustment parameters has been developed. This approach provided a reliable and efficient prediction method for blister growth rate and mechanisms. The model provided a foundation for holistic design based on diffusion and mechanic components to enable better understanding of the debondment of thin elastic films bonded to a metallic substrate.

B Cells, Dendritic Cells, and Macrophages Are Required To Induce an Autoreactive CD4 Helper T Cell Response in Experimental Epidermolysis Bullosa Acquisita

In autoimmune bullous dermatoses (AIBD), autoantibodies induce blisters on skin or mucous membranes, or both. Mechanisms of continued autoantibody production and blistering have been well characterized using AIBD animal models. Mechanisms leading to the initial autoantibody production, however, have not been investigated in detail. Epidermolysis bullosa acquisita (EBA) is an AIBD associated with autoantibodies to type VII collagen (COL7). The majority of EBA patients' sera recognize the noncollagenous domain 1, including the von Willebrand factor A-like domain 2 (vWFA2). In experimental EBA induced by immunization with GST-COL7, disease manifestation depended on the genetic background, a Th1 polarization, and the GST-tag. In this model, nude mice neither produced autoantibodies nor blisters. It has remained uncertain which APC and T cell subsets are required for EBA induction. We established a novel EBA model by immunization with vWFA2 fused to intein (lacking the GST-tag). All tested mouse strains developed autoantibodies, but blisters were exclusively observed in mice carrying H2s. In immunized mice, CD4 T cells specific for vWFA2 were detected, and their induction required presence of B cells, dendritic cells, and macrophages. Anti-vWFA2 autoantibodies located at the lamina densa bound to the dermal side of salt-split skin and induced blisters when transferred into healthy mice. Absence of CD8 T cells at time of immunization had no effect, whereas depletion of CD4 T cells during the same time period delayed autoantibody production and blisters. Collectively, we demonstrate the pathogenic relevance of Abs targeting the vWFA2 domain of COL7 and show the requirement of APC-induced CD4 T cells to induce experimental EBA.

Bullous pemphigoid: role of complement and mechanisms for blister formation within the lamina lucida

Bullous pemphigoid (BP), an autoimmune subepidermal blistering skin disease, demonstrates tense blisters with or without widespread erythema, blistering along the lamina lucida, immunoglobulin G and/or complement deposits at the basement membrane zone, and the presence of circulating autoantibodies against hemidesmosomal molecules. These autoantibodies usually react against 180-kDa and/or 230-kDa proteins, designated as BP180 and BP230, respectively. The precise blistering mechanisms after autoantibodies bind to antigens are not fully understood. Immune complexes are thought to initially activate the complement cascade, which may induce activation of proteases and/or cytokines and cause dermal-epidermal separation. However, why does separation run specifically within the lamina lucida in a space as narrow as 500nm wide? This review mainly focuses on the possible mechanisms of BP-specific blistering and how separation occurs along the lamina lucida, based on existing evidence.

Pemphigus IgG treated keratinocytes are susceptible to herpes simplex virus induced cell dissociation, but protective to virus replication.

Patients with mucosal pemphigus vulgaris (PV), often develop atypical mucosal vesicles and erosions due to herpes simplex virus (HSV) infection. Notably, HSV infections trigger acantholysis. We aimed to examine the HSV effects on blistering mechanisms of PV. Firstly, we evaluated the additive effect of HSV infection to PV-IgG induced acantholysis and actin cytoskeleton reorganization. Cultured cell sheets of keratinocytes were incubated with 0.1mg/ml of anti-desmoglein (Dsg) 3 antibodies, which were PV-IgG and AK23 monoclonal antibody, for 24hours.

Hydrogen-induced blistering mechanisms in thin film coatings

We report on the mechanisms of hydrogen-induced blistering of multilayer coatings. Blister formation is a result of highly localized delamination occurring at the two outermost metal-on-silicon interfaces. The number, size, and type of blisters formed varied depending on the composition and ion energy of the incident flux. The results are explained in terms of the multilayer structure being simultaneously susceptible to blistering via two independent mechanisms. A high density of small blisters developed when relatively energetic (several 100 eV) ions were present. Independently, a hydrogenation process that was facilitated by the presence of a small flux of low energy ions (≤50 eV) induced a low density of large blisters.

Formation of blisters in kapton polymer by the effect of 1.25 MeV gamma irradiation

AbstractThe surface morphology, chemical, optical, and structural response of 1.25 MeV gamma rays irradiation at various doses ranging from 16 to 300 kGy on Kapton polymer samples were studied by using scanning electron microscope (SEM), Fourier Transform Infrared (FTIR), ultraviolet/visible absorption (UV/VIS) and X‐ray diffraction (XRD). The morphology study shows the blisters formation on the Kapton polymer surface due to 1.25 MeV gamma rays irradiation at ambient temperature. This observation provides a basis for the quantitative evaluation of FTIR results obtained for thermally stable polymer on the chemical bond deterioration with increasing gamma irradiation. The blistering mechanism is correlated with the internal gases (CO, H2) released due to gamma radiation induced damages. The recorded UV–VIS spectrum shows a maximum absorption around the wavelength 540 nm. However, the nature of the spectra does not change due to gamma irradiation but a shift in absorption edge towards the higher wavelength side has been observed with increasing dose. The optical data shows an increase in the calculated band gap at the highest dose. The diffraction pattern of virgin sample shows that polymer is semicrystalline, but due to irradiation, a decrease in the peak intensity and FWHM and an increase in the crystallite size at the highest dose level of 300 kGy have been observed. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

Targeting of desmoglein 1 in exfoliative toxin-mediated disease

Exfoliative toxin (ET) is secreted by Staphylococcus aureus and has long been known to cause localized or widespread epidermal blistering in humans termed bullous impetigo or staphylococcal scalded-skin syndrome, respectively. While initial hypotheses suggested that ET was a superantigen, sequence and crystallographic analysis characterized the toxin as a serine protease. More recent work determined that ET cleaves a desmosomal cadherin, desmoglein (Dsg)1. This discovery explained the mechanism of toxin-induced blistering, since Dsg1 proteolysis compromises desmosomes, which link keratinocytes and support epidermal integrity. Here, we review clinical findings in ET-mediated disease, the characterization of ET, the molecular pathogenesis of bullous impetigo/staphylococcal scalded-skin syndrome, the structure and function of Dsg1, and current and potential treatments of ET-mediated disease.

Apoptolysis: a novel mechanism of skin blistering in pemphigus vulgaris linking the apoptotic pathways to basal cell shrinkage and suprabasal acantholysis

Understanding the acantholytic pathways leading to blistering in pemphigus vulgaris (PV) is a key to development of novel treatments. A novel paradigm of keratinocyte damage in PV, termed apoptolysis, links the suprabasal acantholytic and cell death pathways to basal cell shrinkage rendering a 'tombstone' appearance to PV lesions. In contrast to apoptolysis, the classic keratinocyte apoptosis mediating toxic epidermal necrolysis causes death and subsequent sloughing of the entire epidermis. Apoptolysis includes five consecutive steps. (1) Binding of autoantibodies to PV antigens. (2) Activation of EGF receptor, Src, mTOR, p38 MAPK and other signalling elements downstream of ligated antigens, elevation of intracellular calcium and launching of the cell death cascades. (3) Basal cell shrinkage due to: (i) collapse and retraction of the tonofilaments cleaved by executioner caspases; and (ii) dissociation of interdesmosomal adhesion complexes caused by phosphorylation of adhesion molecules. (4) Massive cleavage of cellular proteins by activated cell death enzymes leading to cell collapse, and tearing off desmosomes from the cell membrane stimulating secondary autoantibody production. (5) Rounding up and death of acantholytic cells. Thus, the structural damage (acantholysis) and death (apoptosis) of keratinocytes are mediated by the same cell death enzymes. Appreciation of the unifying concept of apoptolysis have several important implications: (i) linking together a number of seemingly unrelated events surrounding acantholysis; (ii) opening new avenues of investigation into the pathomechanism of pemphigus; and (iii) creating new approaches to the treatment of pemphigus based on blocking the signalling pathways and enzymatic processes that lead to blistering.

Blistering kinetics of GaN by hydrogen implantation at high temperature

The hydrogen ion implantation condition for the ion-cut process in wurtzite-phase GaN and the associated mechanisms of surface blistering of GaN films were investigated. The hydrogen ions were implanted at 40 keV with fluences in the range of (1.5–5) × 10 17 H +/cm 2 over a wide temperature range (RT-450 °C), and at 60 keV at room temperature with fluences in the range of (3–5) × 10 17 H +/cm 2. The influences of the ion fluence, implant temperature and the post-implantation annealing conditions on blistering process were studied. Optical microscopy, field emission scanning electron microscopy (FE-SEM), high resolution X-ray diffraction (HRXRD), Rutherford backscattering spectrometry/channeling (RBS/C), and cross-sectional transmission electron microscopy (XTEM) were used to investigate splitting kinetics, and the optimum conditions for achieving blistering only after post-implantation annealing were determined for the GaN ion-cut process. The optimum fluence for the GaN blistering by hydrogen implantation and subsequent low temperature annealing (250–350 °C) was in the (2–3) × 10 17 H +/cm 2 range within the implantation temperature window of 150–300 °C with activation energies in the range of 1.0–1.6 eV depending on the implanted ion fluence and implant temperature.

A study of hydrogen blistering mechanism for Molybdenum by Tritium radio-luminography

In order to study blistering mechanisms of Molybdenum (Mo), hydrogen distributions at and around blisters formed on Mo surfaces are examined by Tritium (T) radio-luminography or autoradiography (TARG). TARG shows that large amount of hydrogen (T) is accumulated at and near grain boundaries and some blisters are covered with Ag precipitates representing T under the blister skins. Two independent types of blistering mechanisms seem to occur on Mo surface simultaneously. One is typical blistering due to bubble coalescence accompanying plastic deformation of the blister skins and only very thin blister skins allow T detection by TARG. Another is exfoliation or cracking of a grain caused by mechanical fracturing of the grain boundaries and/or defect clusters due to brittle nature of Mo, remaining tritium on the fractured surface.

Differential gene expression profiling of mouse skin after sulfur mustard exposure: Extended time response and inhibitor effect

Sulfur mustard (HD, SM), is a chemical warfare agent that within hours causes extensive blistering at the dermal–epidermal junction of skin. To better understand the progression of SM-induced blistering, gene expression profiling for mouse skin was performed after a single high dose of SM exposure. Punch biopsies of mouse ears were collected at both early and late time periods following SM exposure (previous studies only considered early time periods). The biopsies were examined for pathological disturbances and the samples further assayed for gene expression profiling using the Affymetrix microarray analysis system. Principal component analysis and hierarchical cluster analysis of the differently expressed genes, performed with ArrayTrack showed clear separation of the various groups. Pathway analysis employing the KEGG library and Ingenuity Pathway Analysis (IPA) indicated that cytokine–cytokine receptor interaction, cell adhesion molecules (CAMs), and hematopoietic cell lineage are common pathways affected at different time points. Gene ontology analysis identified the most significantly altered biological processes as the immune response, inflammatory response, and chemotaxis; these findings are consistent with other reported results for shorter time periods. Selected genes were chosen for RT-PCR verification and showed correlations in the general trends for the microarrays. Interleukin 1 beta was checked for biological analysis to confirm the presence of protein correlated to the corresponding microarray data. The impact of a matrix metalloproteinase inhibitor, MMP-2/MMP-9 inhibitor I, against SM exposure was assessed. These results can help in understanding the molecular mechanism of SM-induced blistering, as well as to test the efficacy of different inhibitors.

Mechanisms of blistering and chipping of a scratch-resistant coating

In most cases, scratching of the surface of a polymeric glass elicits brittle behavior. Industrial solutions have been successfully used to improve the scratch resistance of polymeric glasses and a common way is to coat the substrate with a thin film. However, one of the limitations of this method is the risk of cracking and chipping. The origin of the success of the coating technique is still of great research interest and further work will be required to explain the improvement in scratch resistance and predict the cracking in anti-scratch coatings. The present study contributes to these aims. Using a single-asperity scratching device allowing in situ observation of the scratch, the fracturing of a thin (3.5 μm) nano-composite coating deposited on a viscoelastic–viscoplastic substrate (polycarbonate) was investigated under different conditions of temperature and scratching speed. Four types of fracture mechanisms were observed, depending on these two variables. The processes involved in deformation of the system were: (i) delamination (blister formation) and fracture (chipping) of the coating and (ii) viscoelastic–viscoplastic deformation of the substrate. Image analyses were performed on video sequences of the different processes leading to damage of the film. The quantitative results are discussed in terms of the damage mechanisms involved.

Hydrogen blistering of silicon: Progress in fundamental understanding

AbstractWhen silicon is implanted with a sufficient concentration of H ions, at low to moderate temperature, and subsequently annealed at high temperature, dome‐shaped gas‐filled blisters and/or craters of exploded blisters appear on the surface. Under particular conditions, blistering can be produced by plasma hydrogenation as well. The phenomenon is another facet of hydrogen behaviour in silicon, a question with both fundamental and applied implications. Blistering is at the origin of the “ion‐cutting” process for the fabrication of silicon‐on‐insulator and other heterostructures; this process is particularly useful whenever atomically sharp interfaces between layers are required. The novelty and vast potential of this process has spurred since the mid‐1990's a burst of experimental activity on blistering. The purposes of those works were either to improve or extend the ion‐cut process, or to clarify its underlying mechanisms. In “mechanisms”, the plural is used to convey the fact that it is a multi‐step phenomenon. Because of this complexity, the theoretical work, in comparison, is far less abundant. Hydrogen blistering of silicon is qualitatively understood in broad terms: H being insoluble in Si, it tends to segregate into cavities which grow and coalesce at high temperature, and the H2 pressure in the cavities finally deforms the surface. In fact, our understanding of the microscopic mechanisms has progressed much beyond that level thanks to the sophisticated work that has been carried out using techniques such as transmission electron microscopy, Rutherford backscattering in the channelling mode, infrared spectroscopy of local vibrational modes, stress and strain measurements, and others. The effects of n‐ or p‐doping, He ion coimplantation, and isotope substitution have also greatly helped in discriminating between different hypotheses. After a review of the most relevant experimental facts, the blistering mechanisms that have been proposed in the literature will be discussed and their conformity with the data assessed. Finally an attempt will be made to identify the key questions and suggest a few avenues for future work. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

Review Article: Hydrogen blistering of silicon: Progress in fundamental understanding

AbstractThe understanding of blistering mechanisms at the fundamental, atomic‐scale level is still not complete, but large strides towards that goal have been made in the last decade. In this issue's Review Article [1] Bernard Terreault gives a comprehensive survey of this progress, discussing the current questions as well as outlining suggestions for future work.The related cover picture shows atomic force micrographs of a variety of surface morphologies obtained by hydrogen ion implantation into silicon followed by rapid thermal annealing. In this particular case, the ions were implanted through PMMA masks of decreasing width (from left to right, 6 μm, 1 μm, 600 nm and 150 nm) [2]. This is but one application of blistering, the most common being ion‐cutting and layer transfer as used in the commercial production of silicon‐on‐insulator wafers.The author is Honorary retired Professor at the EMT (Energy, Materials, Telecom) Center of the Institut National de la Recherche Scientifique (Université du Québec).Another feature included in the current issue is the Editor's Choice contribution ‘Optical and micro‐analytical study of a copper–conjugated polymer composite’ by Kaushik Mallik et al. [3], where the authors investigate a nanoscale fiber network for potential application in microelectronic systems.

Proton Implantation Mechanism in GaN Layer Transfer by Using the Ion-Cut Process

The proton implantation condition for the ion-cut process in wurtzite-phase GaN and the associated mechanisms of surface blistering of GaN films were investigated. Etch-pit density (EPD) measurements, photoluminescence (PL) spectroscopy, and high resolution X-ray diraction (HRXRD) were used to investigate the crystalline quality of the as-grown GaN epi-wafers. The proton beam was implanted at 60 keV with fluences in the range of 3 5 ◊ 10 17 H + /cm 2 at room temperature. The influences of the crystallinity of the GaN wafers, the ion fluence and the post-implantation annealing conditions (200 450 C) on the blistering process were studied. Optical microscopy, field emission scanning electron microscopy (FE-SEM), HRXRD, Rutherford backscattering Spectrometry (RBS)/channeling (RBS/C), and cross-sectional transmission electron microscopy (XTEM) were used to investigate splitting kinetics, and the optimum conditions for achieving exfoliation only after post-implantation annealing were determined for the GaN ion-cut process. Our results suggest that the ion-cut process is sensitive to both the implant fluence and the annealing conditions, however, so far as the measured crystal quality is concerned, against our expectations, there was no notable influence on the blistering property. The optimum post-implantation annealing temperature was less than 350 C, and low temperature splitting is of importance for layer transfer between dissimilar materials with very dierent thermal expansion coecients.

Mechanisms of retention and blistering in near-surface region of tungsten exposed to high flux deuterium plasmas of tens of eV

The mechanisms of hydrogen retention and blistering in tungsten exposed to high flux deuterium plasmas of tens of eV were studied with a variety of techniques, such as TEM/SEM and TDS. Cross-sectional TEM observations showed that small blisters with diameters around 30 nm and microcracks formed in the near-surface region before the formation of larger blisters with diameters up to a few microns (comparable to grain sizes). The TDS results indicated that deuterium mainly existed in the molecular form in tungsten after the plasma exposure. These results suggest that crystal defects like vacancies could be generated by the intrusion of a large number of hydrogen isotope atoms in the near-surface region of tungsten.

Creating nanostructures on silicon using ion blistering and electron beam lithography

We have investigated the patterning of silicon surfaces using ion blistering in conjunctionwith e-beam lithography. Variable width (150–5000 nm) trenches were first written in500 nm thick PMMA resist spin coated on silicon, using an electron beam. Next, 10 keVH2+ ions were implanted to various fluences through the masks. The resistwas then removed and the samples were rapidly thermally annealed at900 °C. The resulting surface morphologies were investigated by atomic force microscopy. In thewider trenches, round blisters with 600–900 nm diameter are observed, which are similar tothose observed on unmasked surfaces. In submicron trenches, there is a transition inmorphology, caused by the proximity to the border. The blisters are smaller and they aredensely aligned along the trench direction (‘string of pearls’ pattern). Unusual blistergeometries are observed in the narrowest trenches (150 nm) at higher H doses(≥1 × 1017 H cm−2)—such as tubular blisters aligned along the trench. It was also found that for H doses of≥6 × 1016 H cm−2 the surface swells uniformly, which has implications for the blistering mechanism. Theprospects for accomplishing ion cutting, layer transfer and bonding of finely delineatedpatterns of silicon onto another material are discussed in the light of the above results.

Effects of 50 MeV Li3+ Ion Irradiation on Kapton Films

Blisters formation on the surface of kapton film has been observed due to 50 MeV Li3+ ion irradiation up to the fluence of 1.04×1014 ions/cm2 at ambient temperature. This investigation provides a foundation for a quantitative evaluation of the FTIR results for thermally stable polymer on the chemical bond deterioration with irradiation fluences. The blistering mechanism is correlated with the internal gases (CO, H2) released due to Li3+ ion induced radiation damage. The Vicker's micro‐hardness testing has been carried out to study the mechanical behavior of irradiated films at room temperature. It is observed that the true bulk hardness of the film was obtained at loads greater than 400 mN. The hardness of the film increases significantly as fluence increases.

Substructures of Gas-Ion-Irradiation-Induced Surface Blisters in Silicon Studied by Cross-Sectional Transmission Electron Microscopy

Internal structures of surface blisters and their precursors in Si formed by H + , D + and He + irradiation were examined by cross-sectional transmission electron microscopy (XTEM). The skin structures of H + -D + - and He + -blisters reflected the difference in the damage accumulation, and chemical interaction between the implant ion and silicon. These differences had a direct influence on the defect structures of the damaged layer, which played essential roles in the blistering mechanisms. It was found that blister skin thickness derived by grazing incidence electron microscopy (GIEM) and electron energy-loss spectroscopy, (EELS) was underestimated compared to direct measurement by XTEM. The origin of this discrepancy is discussed.

Granulocyte‐derived elastase and gelatinase B are required for dermal–epidermal separation induced by autoantibodies from patients with epidermolysis bullosa acquisita and bullous pemphigoid

Epidermolysis bullosa acquisita (EBA) and bullous pemphigoid (BP) are two clinically and immunologically distinct autoimmune subepidermal blistering skin diseases associated with IgG autoantibodies against the dermal-epidermal junction. BP antibodies are directed against the hemidesmosomal antigens BP180 and BP230, and those in patients with EBA target type VII collagen, a major component of anchoring fibrils. While the pathogenetic mechanisms of subepidermal blistering in BP have been previously studied using a passive transfer mouse model, the effector pathways of blister formation in EBA are largely unknown. Autoantibodies to type VII collagen and BP180 have recently been shown to induce leucocyte-mediated subepidermal cleavage in cryosections of human skin. The aim of the present study was to identify human leucocyte protease(s) instrumental in dermal-epidermal separation induced by autoantibodies to type VII collagen and BP180. When incubated with cryosections of human skin pretreated with IgG from patients with EBA or BP but not from patients with anti-laminin 5 mucous membrane pemphigoid or healthy controls, granulocytes were recruited to the dermal-epidermal junction and induced subepidermal splits. A combination of broad-range protease inhibitors as well as inhibitors of serine and matrix metalloproteases completely abolished dermal-epidermal separation induced by EBA or BP autoantibodies. When characterizing the proteases involved more specifically, selective inhibition of human leucocyte elastase or gelatinase B/MMP-9 was also found to result in suppression of blistering. These findings strongly suggest that elastase and gelatinase B are essential for granulocyte-mediated proteolysis resulting in dermal-epidermal separation in EBA and BP patients' skin.