Dr Ella Schneider

Background: Combining imaging modalities at high spatial resolution is needed to gain a comprehensive understanding of disease pathogenesis and therapeutics. Specifically, it is desirable to perform label free imaging of lipids, proteins and elements at sub-micron spatial resolution and to detect small molecules with high chemical specificity. This work addresses this challenge by developing a workflow for carrying out stimulated Raman scattering (SRS) microscopy, desorption electrospray ionisation (DESI) and MeV ion beam analysis (IBA) on the same tissue section. Results: The first challenge was to find a substrate compatible with all three imaging modalities. It was found that PET membranes can be used to image tissues using all three techniques. Next, a strategy for performing the techniques in sequence was developed. It was found that prior SRS analysis has no detectable effect on subsequent DESI or PIXE imaging, and that DESI does not delocalise elements in skin tissue; therefore the techniques can be performed on the same section of tissue in the order SRS < DESI < PIXE. This work also shows that a methanol:ethanol DESI spray solvent can be used to detect biologically relevant lipids in negative ion mode. Significance: The compatibility of SRS with PET-mounted tissues opens the possibility of sequential analysis using laser capture microdissection or other X-ray spectrometry techniques. Fresh frozen porcine skin was used to highlight the ability to correlate structural, chemical and elemental information, highlighting the co-localisation of lipid hotspots (SRS), with chemical characterisation from DESI and calcium deposits (PIXE) in follicular structures.

Nickel is recognized as a potent skin sensitizer and a common cause of contact dermatitis. Nickel and its compounds are often associated with particulate matter in industrial settings. This study aimed to evaluate the effects of nickel oxide particulate matter (NiOPM) using in vitro skin models, and to compare the effects of NiSO4 topical application on healthy versus atopic dermatitis–sensitized skin. Key endpoints included histological analysis, cell viability, cytokine release, proliferation index, and protein expression. The results revealed that the reconstructed epidermal tissue representing healthy skin was properly stratified. After 24hours of exposure to NiOPM (0.4 - 4.6mg/cm2), histological analysis and viability data (>50%) indicated a lack of cytotoxicity related to irritation. However, ion beam analysis, immunofluorescence, cell proliferation (Ki67 marker), and inflammatory signaling (IL-1α, IL-8) suggest that prolonged exposure may be associated with increased epidermal permeability and oxidative stress, identifying NiOPM as a possible long-term sensitizer. In addition, comparative treatments of NiOPM vs. NiSO4 on models of healthy epidermis and with atopic epidermis, exposed for up to 72hours, demonstrate the damaging effect of NiSO4 as early as the first 24hours. Also, the results suggest differential effects on proliferative cell presence and loricrin expression. These findings indicate that elucidating the sensitization pathways of nickel is complex. The physicochemical characteristics of Ni compounds are closely related to exposure time, skin permeation capacity, and cellular damage. [Display omitted] •NiSO4 and NiO are skin sensitizers; NiSO4 causes earlier in vitro damage.•NiO particulate matter penetrates skin within 24h, confirmed by ion beam analysis.•MTT assay may underestimate NiO effects, despite no cytotoxicity up to 72h.•IL-1α, IL-8, loricrin, and Ki67 changes suggest NiO-induced skin stress.•Nickel compounds may cause atopic dermatitis by property-dependent mechanisms.

We have investigated the use of conventional ion implantation to fabricate enriched 28 Si layers for use in quantum computers. The final compositions of samples enriched using ultra-low energy (800 eV and 2 keV) and low energy (20 keV) 28 Si implants of varying fluences (1x10 16-3.8x10 17 cm-2) using two different implanters were measured using channelled Rutherford Backscattering Spectroscopy. The dynamic, binary collision approximation program TRIDYN was used to model the implantation profiles to guide the analysis of the RBS spectra. It was found that ultra-low energy implants achieved high 28 Si enrichment levels but were heavily contaminated with oxygen due to poor vacuum in the implanter wafer end station. It was shown that oxidation could be reduced by using an accelerator with an end station with better vacuum and increasing the implant energy to 20 keV. However, TRIDYN simulations predict that the best 28 Si enrichment levels that could be achieved under these conditions would saturate at ~99.2 % due to self-sputtering. We modelled a range of conditions with TRIDYN and so recommend low energies (99.9 %) with the lowest possible fluences (~5-10x10 17 cm-2).

28Si enrichment is crucial for production of group IV semiconductor-based quantum computers. Cryogenically cooled, monocrystalline 28Si is a spin-free, vacuum-like environment where qubits are protected from sources of decoherence that cause loss of quantum information. Currently, 28Si enrichment techniques rely on deposition of centrifuged SiF4 gas, the source of which is not widely available, or bespoke ion implantation methods. Previously, conventional ion implantation into naturalSi substrates has produced heavily oxidized 28Si layers. Here we report on a novel enrichment process involving ion implantation of 28Si into Al films deposited on native-oxide free Si substrates followed by layer exchange crystallization. We measured continuous, oxygen-free epitaxial 28Si enriched to 99.7%. Increases in isotopic enrichment are possible, and improvements in crystal quality, aluminum content, and thickness uniformity are required before the process can be considered viable. TRIDYN models, used to model 30 keV 28Si implants into Al to understand the observed post-implant layers and to investigate the implanted layer exchange process window over different energy and vacuum conditions, showed that the implanted layer exchange process is insensitive to implantation energy and would increase in efficiency with oxygen concentrations in the implanter end-station by reducing sputtering. Required implant fluences are an order of magnitude lower than those required for enrichment by direct 28Si implants into Si and can be chosen to control the final thickness of the enriched layer. We show that implanted layer exchange could potentially produce quantum grade 28Si using conventional semiconductor foundry equipment within production-worthy time scales.

In this work, we used a combination of photoluminescence (PL), high resolution X-ray diffraction (XRD), and Rutherford backscattering spectrometry (RBS) techniques to investigate material quality and structural properties of MBE-grown InGaAsBi samples (with and without an InGaAs cap layer) with targeted bismuth composition in the 3%–4% range. XRD data showed that the InGaAsBi layers are more homogeneous in the uncapped samples. For the capped samples, the growth of the InGaAs capped layer at higher temperature affects the quality of the InGaAsBi layer and bismuth distribution in the growth direction. Low-temperature PL exhibited multiple emission peaks; the peak energies, widths, and relative intensities were used for comparative analysis of the data in line with the XRD and RBS results. RBS data at a random orientation together with channeled measurements allowed both an estimation of the bismuth composition and analysis of the structural properties. The RBS channeling showed evidence of higher strain due to possible antisite defects in the capped samples grown at a higher temperature. It is also suggested that the growth of the capped layer at high temperature causes deterioration of the bismuth-layer quality. The RBS analysis demonstrated evidence of a reduction of homogeneity of uncapped InGaAsBi layers with increasing bismuth concentration. The uncapped higher bismuth concentration sample showed less defined channeling dips suggesting poorer crystal quality and clustering of bismuth on the sample surface.

The metallome has been involved in the pathological investigation into ocular tissue for decades; however, as technologies advance, more information can be ascertained from individual tissue sections that were not previously possible. Herein, a demonstration of complementary techniques has been utilized to describe the distribution and concentrations of essential metals in both wildtype (WT) and rhodopsin (Rho−/−) ocular tissues. The multimodal approach described is an example of complementary datasets that can be produced when employing a multifaceted analytical approach. Heterogenous distributions of copper and zinc were observable within both WT and Rho−/− tissue by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), and the distributions of further trace elements notoriously problematic for ICP-MS analysis (phosphorous, Sulfur, chlorine, potassium, calcium, iron, and aluminum) were analysed by particle-induced X-ray emission (PIXE).

The introduction of strain into semiconductors offers a well-known route to modify their band structure. Here, we show a single-step procedure for generating such strains smoothly and deterministically, over a very wide range, using a simple, easily available, highly scalable, ion implantation technique to control the degree of amorphization in and around single-crystal membranes. The amorphization controls the density of the material and thus the tension in the neighboring crystalline regions. We have demonstrated up to 3.1% biaxial tensile strain and 8.5% uniaxial strain in silicon, based on micro-Raman spectroscopy. This method achieves strain levels never previously reached in mesoscopic defect-free, crystalline silicon structures. The flexible, gently controllable, single-step process points toward very high mobility complementary metal-oxide-semiconductor devices and easy fabrication of direct-bandgap germanium for silicon-compatible optoelectronics.

We are investigating a novel enrichment process that could allow the use of industrial complementary metal-oxide-semiconductor implanters to manufacture "quantum grade" Si-28 layers for use in quantum computers. Our implanted layer exchange enrichment process leverages conventional deposition-based layer exchange approaches but replaces a step of depositing a Si layer above an Al layer with a Si-28 implant into the top of an Al layer. A subsequent anneal dissolves Si into Al beneath the implanted region where Si diffuses and either epitaxially grows onto the substrate or forms poly-crystals in the Al [Schneider and England, ACS Appl. Mater. Interfaces 15, 21609 (2023)]. We have developed a qualitative model using simple assumptions and boundary conditions to estimate characteristic times and rates of epitaxy or poly-crystallization for this novel layer exchange process. We have used the model to explain crystallization outcomes reported in this paper and previously. We find that the absence of an oxide boundary layer separating Si and Al allows Si diffusion to become established within the first second of all the anneals studied and that crystallization actually completes during the temperature ramp of most of the anneals. The rapid evolution of Si supersaturation in Al beneath the implanted layer explains the ratios of epitaxial growth to poly-crystallization observed after these anneals. We use this understanding to propose the implant layer exchange conditions that could produce the highest quality mono-crystalline quantum grade Si.