Thick, defect free epitaxial layers grown using industry standard techniques are a fundamental requirement for the widespread adoption of fully vertical power devices based on ultra wide bandgap gallium oxide (Ga2O3). However, metal-organic chemical vapour deposition (MOCVD) of such layers on native beta-Ga2O3 substrates with the largest diameter (001) orientation remains relatively unexplored, and the origins of the reported surface roughening and cracking with increasing thickness are not yet fully understood. To address this, we report a systematic study of MOCVD grown beta-Ga2O3 epilayers deposited at growth rates of 3.5 um/h, with thicknesses from 0.3 to 3.5 um. The epilayers exhibit a relatively smooth but striated surface morphology, with progressively increasing nanometre-scale roughness beyond coalescence and crack formation observed from 1.8 um thickness. High resolution X ray diffraction reveals that, despite growth on (001) substrates, the epilayers adopt a predominantly (-401)-oriented structure from the earliest stages of growth. Rocking curve analysis further indicates a higher degree of in-plane twist than tilt, both decreasing with increasing epilayer thickness. While the epilayer and substrate are lattice-matched along the [010] in plane direction, the epitaxial alignment in the orthogonal epilayer [104] in plane direction imposes, in theory, a maximum tensile in-plane strain of approximately +4.1
In this study, we report on the fabrication and evaluation of gas sensing performance for 3 x 3 graphene pixel array sensors coated with polymers of intrinsic microporosity (PIM-1 and PIM-EA-TB) and Matrimid, a commercial polyimide, for the detection of nitrogen dioxide (NO2). The polymer films, with thicknesses of only 9-11 nm, significantly enhanced the gas sensing performance, demonstrating responses as high as -25.7% compared to a bare graphene response of -10.8%. The gas sensing performance was evaluated in real-time by exposing the sensors to NO2 concentrations from 1 to 50 ppm, along with selectivity tests using ammonia (NH3), nitric oxide (NO), methane (CH4), and carbon dioxide (CO2). In addition to their high sensitivity, the sensors exhibited reduced response times by 56 s. They also demonstrated high selectivity for NO2, with minimal cross-sensitivity to other gases. Furthermore, the polymer membranes exhibited rapid recovery times (114-153 s) and limits of detection in the low parts per billion range, with PIM-EA-TB achieving a detection limit of 0.7 ppb. These features highlight their potential as promising candidates for real-time environmental monitoring of toxic gases, showcasing the potential use of PIMs to enhance the sensitivity and selectivity of graphene-based gas sensors and providing a foundation for further development of cost-effective and reliable NO2 detection systems.
Microneedles (MNs) are micron-sized needles, typically <2 mm in length, arranged either as an array or as single needle. These MNs offer a minimally invasive approach to ocular drug delivery due to their micron size (reducing tissue damage compared to that of hypodermic needles) and overcoming significant barriers in drug administration. While various types of MNs have been extensively researched, significant progress has been made in the use of hollow MNs (HMNs) for ocular drug delivery, specifically through suprachoroidal injections. The suprachoroidal space, situated between the sclera and choroid, has been targeted using optical coherence tomography-guided injections of HMNs for the treatment of uveitis. Unlike other MNs, HMNs can deliver larger volumes of formulations to the eye. This review primarily focuses on the use of HMNs in ocular drug delivery and explores their ocular anatomy and the distribution of formulations following potential HMN administration routes. Additionally, this review focuses on the influence of formulation characteristics (e.g., solution viscosity, particle size), HMN properties (e.g., bore or lumen diameter, MN length), and routes of administration (e.g., periocular transscleral, suprachoroidal, intravitreal) on the ocular distribution of drugs. Overall, this paper highlights the distinctive properties of HMNs, which make them a promising technology for improving drug delivery efficiency, precision, and patient outcomes in the treatment of ocular diseases.
A novel method for determining the yield of bacterial growth using square wave voltammetry and screen printed electrodes is described here. This procedure was shown to be a reliable and accurate way to quickly determine the level of bacterial growth within culturing media and these results suggest that the combination of such sensors and the application of square wave voltammetry is suitable for applications such as within a bioreactor where the rapid determination of bacterial growth may be necessary.
This paper demonstrates the development of carbon-based graphene nanoplatelet (cGNP) electrochemical immunosensor for the detection of immunoglobulin G (IgG). Initially, surface characterization via SEM revealed a smooth surface on the cGNP indicating successful GNP coverage using the drop-casting method. Screening of electrolyte buffers revealed that ferrocyanide and ferricyanide provided a favorable response with a current density of 9.369 mu A. Functionalization of cGNP, was achieved using a 2% APTES solution during a 1-hour incubation period. Electrochemical characterization through cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) demonstrated excellent electrochemical activity when 0.1% bovine serum albumin (BSA) was employed as a blocking agent against 1 mg/ml IgG. Chronoamperometry (CA) confirmed IgG immobilization at a potential of 0.1 V. Notably, the immobilization of IgG resulted in an increase in the charge transfer resistance (Rct) to 69.8 +/- 2.3 Omega, attributed to the hindrance of biological molecules on interfacial electron transfer. Consequently, the proposed cGNP electrochemical immunosensor platform exhibited a robust analytical response, characterized by optimal antibody binding capacity. This superior performance can be attributed to the presence of GNP on the screen-printed carbon electrode (SPCE), which enhanced surface area, conductivity, and overall electrical properties. These attributes make this platform a promising candidate for further research in protein biomarker diagnosis and related applications.
Effective control of device geometry is key to mitigating high localized electric fields in next-generation SiC power devices. Advanced trench processing allows for highly tunable trench-gate architectures in trench MOSFETs. By utilizing a two-step inductively coupled plasma reactive ion etch (ICP-RIE) process, a high degree of trench base corner rounding can be achieved, irrespective of trench opening corner geometry prior to post etch treatments. Sentaurus TCAD device modelling highlights the importance of effective electric field dispersion at the gate oxide using rounded trench corners, while I-V characterization of fabricated trench MOS-capacitor devices demonstrate the influence of trench base corner rounding on gate oxide breakdown.
Transdermal drug delivery systems offer several advantages over conventional oral or hypodermic administration due to the avoidance of first-pass drug metabolism and gastrointestinal degradation as well as patients' convenience due to a minimally invasive and painless approach. A novel transdermal drug delivery system, comprising a combination of transfersomes with either solid silicon or solid polycarbonate microneedles has been developed for the transdermal delivery of aspirin. Aspirin was encapsulated inside transfersomes using a "thin-film hydration sonication" technique, yielding an encapsulation efficiency of approximately 67.5%. The fabricated transfersomes have been optimised and fully characterised in terms of average size distribution and uniformity, surface charge and stability (shelf-life). Transdermal delivery, enhanced by microneedle penetration, allows the superior permeation of transfersomes into perforated porcine skin and has been extensively characterised using optical coherence tomography (OCT) and transmission electron microscopy (TEM). In vitro permeation studies revealed that transfersomes enhanced the permeability of aspirin by more than four times in comparison to the delivery of unencapsulated "free" aspirin. The microneedle-assisted delivery of transfersomes encapsulating aspirin yielded 13-fold and 10-fold increases in permeation using silicon and polycarbonate microneedles, respectively, in comparison with delivery using only transfersomes. The cytotoxicity of different dose regimens of transfersomes encapsulating aspirin showed that encapsulated aspirin became cytotoxic at concentrations of ≥100 μg/mL. The results presented demonstrate that the transfersomes could resolve the solubility issues of low-water-soluble drugs and enable their slow and controlled release. Microneedles enhance the delivery of transfersomes into deeper skin layers, providing a very effective system for the systemic delivery of drugs. This combined drug delivery system can potentially be utilised for numerous drug treatments.
In this paper we study and compare two designs of a temperature sensor monolithically integrated to a vertical SiC JFET. One sensor utilizes the standard JFET P+ aluminum gate implantation scheme. The advantage of this sensor is that the integration with a JFET process flow can be achieved with no additional process steps or mask layers. The other sensor uses a combination P-body and a low energy P+ implantation scheme, typically seen in MOSFETs. Both sensors exploit the variation of resistance with temperature of Al doped SiC. Drift-Diffusion simulations of both designs are carried out at fixed temperatures, exhibiting an excellent ~53% relative reduction in sensor resistance from 300 to 450K. However, neither design shows linear behavior with temperature, beginning to saturate at 450K. Electrothermal simulations are also deployed to verify the sensor robustness as the sensor is locate relatively far from the JFET junction. Due to the high thermal conductivity of SiC, the sensor average temperature follows closely the junction temperature. Current crowding (or 2D effects) close to the contact edges is observed in both sensors. We also deploy a simple analytical model to calculate the resistance as a function of the temperature for both sensors. The model agrees with the drift-diffusion calculations, however due to the 2D nature of current flow, a maximum 19.6% relative error is obtained. In general, both sensors deployed similar relative sensitivity, however the P-body sensor resistance changes in a range of 10.6kΩ to 4.95kΩ compared to 700Ω to 330Ω for the P+ sensor.
Over the last decade, a significant paradigm shift has been observed towards leveraging less invasive biological fluids—such as skin interstitial fluid (ISF), sweat, tears, and saliva—for health monitoring. This evolution seeks to transcend traditional, invasive blood-based methods, offering a more accessible approach to health monitoring for non-specialized personnel. Skin ISF, with its profound resemblance to blood, emerges as a pivotal medium for the real-time, minimally invasive tracking of a broad spectrum of biomarkers, thus becoming an invaluable asset for correlating with blood-based data. Our exploration delves deeply into the development of wearable molecular biosensors, spotlighting dermal sensors for their pivotal roles across both clinical and everyday health monitoring scenarios and underscoring their contributions to the holistic One Health initiative. In bringing forward the myriad challenges that permeate this field, we also project future directions, notably the potential of skin ISF as a promising candidate for continuous health tracking.Moreover, this paper aims to catalyse further exploration and innovation by presenting a curated selection of seminal technological advancements. Amidst the saturated landscape of analytical literature on translational challenges, our approach distinctly seeks to highlight recent developments. In attracting a wider spectrum of research groups to this versatile domain, we endeavour to broaden the collective understanding of its trajectory and potential, mapping the evolution of wearable biosensor technology. This strategy not only illuminates the transformative impact of wearable biosensors in reshaping health diagnostics and personalized medicine but also fosters increased participation and progress within the field. Distinct from recent manuscripts in this domain, our review serves as a distillation of key concepts, elucidating pivotal papers that mark the latest advancements in wearable sensors. Through presenting a curated collection of landmark studies and offering our perspectives on the challenges and forward paths, this paper seeks to guide new entrants in the area. We delineate a division between wearable epidermal and subdermal sensors—focusing on the latter as the future frontier—thereby establishing a unique discourse within the ongoing narrative on wearable sensing technologies.
3D wafer packaging represents a significant component of the total wafer level processing cost. Replacement of the Chemical Mechanical Polishing (CMP) process step with a corresponding dry etch can yield significant time and cost savings. Incorporating equipment already utilized in the 3D integrated wafer packaging process during the subsequent Through Silicon Via (TSV) reveal step, process efficiencies can be achieved, with overall die yields being maintained. Using dry etch technology to treat a 200nm rough back-ground silicon surface, a smooth surface with a peak to valley roughness of less than 6nm is demonstrated. This patented process differs from other dry etch smoothing techniques in that it aims to eliminate any visual grind marks rather than just reducing the surface roughness. The elimination of visible grind marks is critical in later optical inspection where they are falsely identified as defects. The quality of the surface is equivalent to that of a CMP processed wafer and as such, this process has been implemented in manufacturing replacing the CMP step. The novel process described combines a surface modification followed by a roughness reduction in an iterative manner to produce a smooth surface without visible grind marks post processing.
IntroductionMicroneedle fabrication was conceptualized in the 1970s as devices for painless transdermal drug delivery. The last two decades have seen considerable research and financial investment in this area with SARS-CoV-2 and other vaccines catalyzing their application to in vivo intradermal vaccine delivery. Microneedle arrays have been fabricated in different shapes, geometries, formats, and out of different materials.Areas coveredThe recent pandemic has offered microneedle platforms the opportunity to be employed as a vehicle for SARS-CoV-2 vaccine administration. Various modes of vaccination delivery and the potential of microneedle array-based vaccines will be presented, with a specific focus placed on recent SARS-CoV-2 research. The advantages of microneedle-based vaccine administration, in addition to the major hurdles to their en masse implementation, will be examined.Expert opinionConsidering the widely acknowledged disadvantages of current vaccine delivery, such as anxiety, pain, and the requirement for professional administration, a large shift in this research sphere is imminent. The SARS-CoV-2 pandemic has catalyzed the development of alternate vaccination platforms, working to avoid the requirement for mass vaccination centers. As microneedle vaccine patches are transitioning through clinical study phases, research will be required to prepare this technology for a more mass production environment.
In this paper we report the progress of our SiC trench etch development using enhanced ICP-based etch technology. Computer modelling of the electric field strength in the gate oxide as a function of corner geometry was used to illustrate trench corner rounding as an effective method to avoid to high gate oxide field strengths. This is an effort to examine a major ongoing issue in device reliability, and to govern future device design.
Infectious disease outbreaks remain an ever‐prevalent global issue. The associated demand for rapid diagnostics and onsite testing will play an increasing and critical role in disease surveillance, prevention of the spread of infection, as well as timely commencement of treatment. Reported here is a graphene–gold nanoparticle hybrid sensor platform technology that is demonstrated for the real‐time detection of viral proteins utilizing low volume samples (5 μL). Hepatitis C virus (HCV) is still an endemic problem worldwide and is used as an exemplar system here to demonstrate the capability of the platform viral detection sensor technology. Hepatitis C virus core antigen (HCVcAg) is a promising marker for point‐of‐care (POC) diagnostic testing for active HCV infection, with the potential to provide a one‐stop diagnosis and trigger for the commencement of treatment. Real‐time electrical resistance measurements are performed using various concentrations of HCVcAg with linear concentration dependence of resistance on HCVcAg concentration over the range of 100–750 pg mL −1 .
Screen printed pH sensors have been developed that utilise conductive carbon/graphene coated with DMSOmelanin for pH sensitivity. Their effectiveness has been demonstrated in buffer solutions and here they have been tested in a mixture of various frequently used culturing media solutions along side live bacteria in order to assess their suitability for monitoring the pH in real world bacterial culturing applications. The results indicate that these sensors can be used to accurately and consistently determine the pH of culturing media solutions at a high sensitivity in the presence of bacterial growth over the biologically relevant range of pH5 to pH8. This sensitivity was consistent between different types of culturing media that the sensor was tested with (brain heart infusion, nutrient and lysogeny broth) as well as pH reference buffer solutions. Therefore based on these findings it can be concluded that this sensor is sufficiently robust and has the potential to be useful in applications such as monitoring the ambient conditions of cultured microorganisms in a bioreactor.
A chromium-containing metal-organic framework (MOF), MIL-101 (Chromium(III) benzene-1,4-dicarboxylate), was used to catalyze the one pot, three component synthesis of some 2,4,5-trisubstituted imidazoles under solvent-free conditions. The advantages of using this heterogeneous catalyst include short reaction time, high yields, easy and quick isolation of catalyst and products, low amount of catalyst needed, and that the addition of solvent, salt, and additives are not needed. This catalyst is highly efficient and can be recovered at least 5 times with a slight loss of efficiency. The structure of the metal-organic frameworks (MOF) was confirmed by X-ray diffraction (XRD) and field emission scanning electron microscopy (FESEM). Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (HNMR) were performed to confirm some of the synthesized products. Experimental data indicated that the optimum amount of catalyst was 5 mg for benzil (1 mmol), 4-chlorobenzaldehyde (1 mmol), and ammonium acetate (2.5 mmol), and the synthetic route to the various imidazoles is performed in 10 min by 95% yield, an acceptable result rivalling those of other catalysts.
An immunosensor capable of high sensitivity detection of beta-amyloid peptides, shown to be a reliable biomarker for Alzheimer's disease, has been developed using screen printed graphene electrodes (SPGEs) modified with ultra-thin layers of polymerised 1,5-diaminonaphthalene (pDAN). Electropolymerization of 1,5-diaminonaphthalene (DAN) was performed to coat the graphene screen printed electrodes in a continuous polymer layer with controlled thickness. The surface characteristics of pristine graphene and polymer modified graphene electrodes were examined using Raman and X-ray photoelectron spectroscopy. The effects of polymer thickness on the electron transfer rates were investigated. An immunosensor for selective detection of beta amyloid peptides Aβ(1-42) was developed via biofunctionalization of the pDAN modified SPGE with the anti-beta amyloid antibody used as the peptide bioreceptor. The immunosensor has been used for specific detection of Aβ(1-42) with a linear range of 1 pg mL-1 to 1000 pg mL-1 and showed 1.4 pg mL-1 and 4.25 pg mL-1 detection and quantification limit, respectively. The biosensor was further validated for the analysis of spiked human plasma. The immunosensor enables rapid, accurate, precise, reproducible and highly sensitive detection of Aβ(1-42) using a low-cost SPGE platform, which opens the possibilities for diagnostic ex vivo applications and research-based real time studies.
Graphene is an ideal material for biosensors due to the large surface area for multiple bonding sites, the high electrical conductivity allowing for high sensitivity, and the high tensile strength providing durability in fabricated sensor devices. For graphene to be successful as a biosensing platform, selectivity must be achieved through functionalization with specific chemical groups. However, the device performance and sensor sensitivity must still be maintained after functionalization, which can be challenging. We compare phenyl amine and 1,5-diaminonaphthalene functionalization methods for chemical vapor deposition grown graphene, both used to obtain graphene modified with amine groups—which is required for surface attachment of highly selective antibody bio-receptors. Through atomic force microscopy (AFM), Raman spectroscopy, and time-of-flight secondary ion mass spectrometry imaging of co-located areas, the chemistry, thickness, and coverage of the functional groups bound to the graphene surface have been comprehensively analyzed. We demonstrate the modification of functionalized graphene using AFM, which unexpectedly suggests the removal of covalently bonded functional groups, resulting in a “recovered” graphene structure with reduced disorder, confirmed with Raman spectroscopy. This removal explains the decrease in the ID/IG ratio observed in Raman spectra from other studies on functionalized graphene after mechanical strain or a chemical reaction and reveals the possibility of reverting to the non-functionalized graphene structure. Through this study, preferred functionalization processes are recommended to maintain the performance properties of graphene as a biosensor.
Graphene-based point-of-care (PoC) and chemical sensors can be fabricated using photolithographic processes at wafer-scale. However, these approaches are known to leave polymer residues on the graphene surface, which are difficult to remove completely. In addition, graphene growth and transfer processes can introduce defects into the graphene layer. Both defects and resist contamination can affect the homogeneity of graphene-based PoC sensors, leading to inconsistent device performance and unreliable sensing. Sensor reliability is also affected by the harsh chemical environments used for chemical functionalisation of graphene PoC sensors, which can degrade parts of the sensor device. Therefore, a reliable, wafer-scale method of passivation, which isolates the graphene from the rest of the device, protecting the less robust device features from any aggressive chemicals, must be devised. This work covers the application of molecular vapour deposition technology to create a dielectric passivation film that protects graphene-based biosensing devices from harsh chemicals. We utilise a previously reported “healing effect” of Al2O3 on graphene to reduce photoresist residue from the graphene surface and reduce the prevalence of graphene defects to improve graphene device homogeneity. The improvement in device consistency allows for more reliable, homogeneous graphene devices, that can be fabricated at wafer-scale for sensing and biosensing applications.
A real-time sensor for the detection of amyl butyrate (AB) utilising human olfactory receptor 2AG1 (OR2AG1), a G-protein coupled receptor (GPCR) consisting of seven transmembrane domains, immobilized onto a graphene resistor is demonstrated. Using CVD graphene as the sensor platform, allows greater potential for more sensitive detection than similar sensors based on carbon nanotubes, gold or graphene oxide platforms. A specific graphene resistor sensor was fabricated and modified via non-covalent π–π stacking of 1,5 diaminonaphthalene (DAN) onto the graphene channel, and subsequent anchoring of the OR2AG1 receptor to the DAN molecule using glutaraldehyde coupling. Binding between the target odorant, amyl butyrate, and the OR2AG1 receptor protein generated a change in resistance of the graphene resistor sensor. The functionalized graphene resistor sensors exhibited a linear sensor response between 0.1–500 pM and high selectively towards amyl butyrate, with a sensitivity as low as 500 fM, whilst control measurements using non-specific esters, produced a negligible sensor response. The approach described here provides an alternative sensing platform that can be used in bioelectronic nose applications.
Electrochemical biosensors using carbon-based electrodes are being widely developed for the detection of a range of different diseases. Since their sensitivity depends on the surface coverage of bioreceptor moieties, it necessarily depends on the surface coverage of amine precursors. Electrochemical techniques, using ferrocene carboxylic acid as a rapid and cheap assay, were used to assess the surface coverage of amino-phenyl groups attached to the carbon electrode. While the number of electrons transferred in the first step of diazotisation indicated a surface coverage of 8.02 ± 0.2 × l0−10 (mol/cm2), and those transferred in the second step, a reduction of nitrophenyl to amino-phenyl, indicated an amine surface coverage of 4–5 × l0−10 (mol/cm2), the number of electrons transferred during attachment of the amine coupling assay compound, ferrocene carboxylic acid, indicated a much lower available amine coverage of only 2.2 × l0−11 (mol/cm2). Furthermore, the available amine coverage was critically dependent upon the number of cyclic voltammetry cycles used in the reduction, and thus the procedures used in this step influenced the sensitivity of any subsequent sensor. Amine coupling of a carboxyl terminated anti-beta amyloid antibody specific to Aβ(1-42) peptide, a potential marker for Alzheimer’s disease, followed the same pattern of coverage as that observed with ferrocene carboxylic acid, and at optimum amine coverage, the sensitivity of the differential pulse voltammetry sensor was in the range 0–200 ng/mL with the slope of 5.07 µA/ng·mL−1 and R2 = 0.98.