Current and Emerging Technology for Continuous Glucose Monitoring.

Diabetes has become a leading cause of death worldwide. Although there is no cure for diabetes, blood glucose monitoring combined with appropriate medication can enhance treatment efficiency, alleviate the symptoms, as well as diminish the complications. For point-of-care purposes, continuous glucose monitoring (CGM) devices are considered to be the best candidates for diabetes therapy. This review focuses on current growth areas of CGM technologies, specifically focusing on subcutaneous implantable electrochemical glucose sensors. The superiority of CGM systems is introduced firstly, and then the strategies for fabrication of minimally-invasive and non-invasive CGM biosensors are discussed, respectively. Finally, we briefly outline the current status and future perspective for CGM systems.

Fabrication of nanostructured transmissive optical devices on ITO-glass with UV1116 photoresist using high-energy electron beam lithography.

High-energy electron beam lithography for patterning nanostructures on insulating substrates can be challenging. For high resolution, conventional resists require large exposure doses and for reasonable throughput, using typical beam currents leads to charge dissipation problems. Here, we use UV1116 photoresist (Dow Chemical Company), designed for photolithographic technologies, with a relatively low area dose at a standard operating current (80 kV, 40-50 µC cm-2, 1 nAs-1) to pattern over large areas on commercially coated ITO-glass cover slips. The minimum linewidth fabricated was ∼33 nm with 80 nm spacing; for isolated structures, ∼45 nm structural width with 50 nm separation. Due to the low beam dose, and nA current, throughput is high. This work highlights the use of UV1116 photoresist as an alternative to conventional e-beam resists on insulating substrates. To evaluate suitability, we fabricate a range of transmissive optical devices, that could find application for customized wire-grid polarisers and spectral filters for imaging, which operate based on the excitation of surface plasmon polaritons in nanosized geometries, with arrays encompassing areas ∼0.25 cm2.

Single-step fabrication of thin-film linear variable bandpass filters based on metal-insulator-metal geometry.

A single-step fabrication method is presented for ultra-thin, linearly variable optical bandpass filters (LVBFs) based on a metal-insulator-metal arrangement using modified evaporation deposition techniques. This alternate process methodology offers reduced complexity and cost in comparison to conventional techniques for fabricating LVBFs. We are able to achieve linear variation of insulator thickness across a sample, by adjusting the geometrical parameters of a typical physical vapor deposition process. We demonstrate LVBFs with spectral selectivity from 400 to 850 nm based on Ag (25 nm) and MgF2 (75-250 nm). Maximum spectral transmittance is measured at ∼70% with a Q-factor of ∼20.

Effects of Ni Deposition on the Electrochemical Properties of CNT/Ni Electrode and Its Application for Glucose Sensing.

A low density CNT forest was fabricated by plasma enhanced chemical vapor deposition, and Ni nanoclusters were well distributed on the sidewall and on top of CNT forest by magnetron sputtering. The Ni deposition time plays an important role in electrochemical properties of the CNT/Ni electrodes, and the optimized deposition time is 150 to 240 s. Cyclic voltammetry and chronoamperometry were used to evaluate the catalytic activities of the CNT/Ni electrodes. The sensitivity of the glucose sensor based on a Ni24OS electrode is able to reach 1433 µA mM(-1) cm(-2), which is much higher than that found using a NiOS electrode.

Assessing the Effect of Twisting and Twisting Fatigue on ZnO:Al Thin Film Performance on PEN and PET Substrates.

This study examines the electromechanical characteristics of aluminium-doped zinc oxide (AZO) films. The films were produced using the RF magnetron sputtering process with a consistent thickness of 150 nm on various polymer substrates. The study focuses on assessing the electro-mechanical failure processes of coated segments using flexible substrates, namely polyethylene naphthalate (PEN) and polyethylene terephthalate (PET), with a specific emphasis on typical cracking and delamination occurrences. This examination involves conducting twisting deformation together with using standardised electrical resistance measurements and optical microscope monitoring instruments. It was found that the crack initiation angle is mostly dependent on the mechanical mismatch between the coating and substrate. Higher critical twisting angle values are observed for the AZO/PEN film during twisting testing. Relative to the perpendicular plane of the untwisted sample, it was found that cracks initiated at a twist angle equal to 42° ± 2.1° and 38° ± 1.7° for AZO/PEN and AZO/PET, respectively, and propagated along the sample length. SEM images indicate that the twisting motion results in deformation in the thin film material, leading to the presence of both types of stress in the film structure. These discoveries emphasise the significance of studying the mechanical properties of thin films under different stress conditions, as it can impact their performance and reliability in real-world applications. The electromechanical stability of AZO was found to be similar on both substrates during fatigue testing. Studying the electromechanical properties of various material combinations is important for selecting polymer substrates and predicting the durability of flexible electronic devices made from polyester.

Prostate cancer detection through unbiased capture of methylated cell-free DNA.

Prostate cancer screening using prostate-specific antigen (PSA) has been shown to reduce mortality but with substantial overdiagnosis, leading to unnecessary biopsies. The identification of a highly specific biomarker using liquid biopsies, represents an unmet need in the diagnostic pathway for prostate cancer. In this study, we employed a method that enriches for methylated cell-free DNA fragments coupled with a machine learning algorithm which enabled the detection of metastatic and localized cancers with AUCs of 0.96 and 0.74, respectively. The model also detected 51.8% (14/27) of localized and 88.7% (79/89) of patients with metastatic cancer in an external dataset. Furthermore, we show that the differentially methylated regions reflect epigenetic and transcriptomic changes at the tissue level. Notably, these regions are significantly enriched for biologically relevant pathways associated with the regulation of cellular proliferation and TGF-beta signaling. This demonstrates the potential of circulating tumor DNA methylation for prostate cancer detection and prognostication.

Near-ultraviolet zinc oxide nanowire sensor using low temperature hydrothermal growth.

Two near-ultraviolet (UV) sensors based on solution-grown zinc oxide (ZnO) nanowires (NWs) which are only sensitive to photo-excitation at or below 400 nm wavelength have been fabricated and characterized. Both devices keep all processing steps, including nanowire growth, under 100 °C for compatibility with a wide variety of substrates. The first device type uses a single optical lithography step process to allow simultaneous in situ horizontal NW growth from solution and creation of symmetric ohmic contacts to the nanowires. The second device type uses a two-mask optical lithography process to create asymmetric ohmic and Schottky contacts. For the symmetric ohmic contacts, at a voltage bias of 1 V across the device, we observed a 29-fold increase in current in comparison to dark current when the NWs were photo-excited by a 400 nm light-emitting diode (LED) at 0.15 mW cm(-2) with a relaxation time constant (τ) ranging from 50 to 555 s. For the asymmetric ohmic and Schottky contacts under 400 nm excitation, τ is measured between 0.5 and 1.4 s over varying time internals, which is ~2 orders of magnitude faster than the devices using symmetric ohmic contacts.

A critical review of glucose biosensors based on carbon nanomaterials: carbon nanotubes and graphene.

There has been an explosion of research into the physical and chemical properties of carbon-based nanomaterials, since the discovery of carbon nanotubes (CNTs) by Iijima in 1991. Carbon nanomaterials offer unique advantages in several areas, like high surface-volume ratio, high electrical conductivity, chemical stability and strong mechanical strength, and are thus frequently being incorporated into sensing elements. Carbon nanomaterial-based sensors generally have higher sensitivities and a lower detection limit than conventional ones. In this review, a brief history of glucose biosensors is firstly presented. The carbon nanotube and grapheme-based biosensors, are introduced in Sections 3 and 4, respectively, which cover synthesis methods, up-to-date sensing approaches and nonenzymatic hybrid sensors. Finally, we briefly outline the current status and future direction for carbon nanomaterials to be used in the sensing area.

Electric-Field-Resonance-Based Wireless Triboelectric Nanogenerators and Sensors.

Energy harvesting and energy transmission are the key technologies for self-powered systems; thus, the combination of these two is urgently needed. An innovative electric field resonance (EFR)-based wireless triboelectric nanogenerator (TENG) is proposed herein. By integrating the TENG with a capacitive coupler, the output of the TENG can be transmitted wirelessly from the transmitter to the receiver in the form of an oscillating signal with an energy-transfer efficiency of 67.8% for a 5 cm distance. Theoretical models of the EFR-TENG system are established, showing excellent agreement with the experimental results. It is demonstrated that the flexible EFR-TENG worn on the wrist can drive a digital watch wirelessly or light up at least 40 light-emitting diodes in series. The EFR-TENG is further utilized for spontaneous wireless sensing with a transmission distance up to 2.3 m with high system tolerance, showing the great potential of this novel strategy for energy harvesting and real-time wireless sensing applications.

Interfacial immobilization of monoclonal antibody and detection of human prostate-specific antigen.

Antibody orientation and its antigen binding efficiency at interface are of particular interest in many immunoassays and biosensor applications. In this paper, spectroscopic ellipsometry (SE), neutron reflection (NR), and dual polarization interferometry (DPI) have been used to investigate interfacial assembly of the antibody [mouse monoclonal anti-human prostate-specific antigen (anti-hPSA)] at the silicon oxide/water interface and subsequent antigen binding. It was found that the mass density of antibody adsorbed at the interface increased with solution concentration and adsorption time while the antigen binding efficiency showed a steady decline with increasing antibody amount at the interface over the concentration range studied. The amount of antigen bound to the interfacial immobilized antibody reached a maximum when the surface-adsorbed amount of antibody was around 1.5 mg/m(2). This phenomenon is well interpreted by the interfacial structural packing or crowding. NR revealed that the Y-shaped antibody laid flat on the interface at low surface mass density with a thickness around 40 Å, equivalent to the short axial length of the antibody molecule. The loose packing of the antibody within this range resulted in better antigen binding efficiency, while the subsequent increase of surface-adsorbed amount led to the crowding or overlapping of antibody fragments, hence reducing the antigen binding due to the steric hindrance. In situ studies of antigen binding by both NR and DPI demonstrated that the antigen inserted into the antibody layer rather than forming an additional layer on the top. Stability assaying revealed that the antibody immobilized at the silica surface remained stable and active over the monitoring period of 4 months. These results are useful in forming a general understanding of antibody interfacial behavior and particularly relevant to the control of their activity and stability in biosensor development.

Tail state mediated conduction in zinc tin oxide thinfilm phototransistors under below bandgap optical excitation.

We report on the appearance of a strong persistent photoconductivity (PPC) and conductor-like behaviour in zinc tin oxide (ZTO) thinfilm phototransistors. The active ZTO channel layer was prepared by remote plasma reactive sputtering and possesses an amorphous structure. Under sub-bandgap excitation of ZTO with UV light, the photocurrent reaches as high as ~ 10-4 A (a photo-to-dark current ratio of ~ 107) and remains close to this high value after switching off the light. During this time, the ZTO TFT exhibits strong PPC with long-lasting recovery time, which leads the appearance of the conductor-like behaviour in ZTO semiconductor. In the present case, the conductivity changes over six orders of magnitude, from ~ 10-7 to 0.92/Ω/cm. After UV exposure, the ZTO compound can potentially remain in the conducting state for up to a month. The underlying physics of the observed PPC effect is investigated by studying defects (deep states and tail states) by employing a discharge current analysis (DCA) technique. Findings from the DCA study reveal direct evidence for the involvement of sub-bandgap tail states of the ZTO in the strong PPC, while deep states contribute to mild PPC.

Role of ALD Al2O3 Surface Passivation on the Performance of p-Type Cu2O Thin Film Transistors.

High-performance p-type oxide thin film transistors (TFTs) have great potential for many semiconductor applications. However, these devices typically suffer from low hole mobility and high off-state currents. We fabricated p-type TFTs with a phase-pure polycrystalline Cu2O semiconductor channel grown by atomic layer deposition (ALD). The TFT switching characteristics were improved by applying a thin ALD Al2O3 passivation layer on the Cu2O channel, followed by vacuum annealing at 300 °C. Detailed characterization by transmission electron microscopy-energy dispersive X-ray analysis and X-ray photoelectron spectroscopy shows that the surface of Cu2O is reduced following Al2O3 deposition and indicates the formation of a 1-2 nm thick CuAlO2 interfacial layer. This, together with field-effect passivation caused by the high negative fixed charge of the ALD Al2O3, leads to an improvement in the TFT performance by reducing the density of deep trap states as well as by reducing the accumulation of electrons in the semiconducting layer in the device off-state.

A novel split mode TFBAR device for quantitative measurements of prostate specific antigen in a small sample of whole blood.

Easy monitoring of prostate specific antigen (PSA) directly from blood samples would present a significant improvement as compared to conventional diagnostic methods. In this work, a split mode thin film bulk acoustic resonator (TFBAR) device was employed for the first time for label-free measurements of PSA concentrations in the whole blood and without sample pre-treatment. The surface of the sensor was covalently modified with anti-PSA antibodies and demonstrated a very high sensitivity of 101 kHz mL ng-1 and low limit of detection (LOD) of 0.34 ng mL-1 in model spiked solutions. It has previously been widely believed that significant pre-processing of blood samples would be required for TFBAR biosensors. Importantly, this work demonstrates that this is not the case, and TFBAR technology provides a cost-effective means for point-of-care (POC) diagnostics and monitoring of PSA in hospitals and in doctors' offices. Additionally, the accuracy of the developed biosensor, with respect to a commercial auto analyser (Beckman Coulter Access), was evaluated to analyse clinical samples, giving well-matched results between the two methods, thus showing a practical application in quantitative monitoring of PSA levels in the whole blood with very good signal recovery.

Novel Tunnel-Contact-Controlled IGZO Thin-Film Transistors with High Tolerance to Geometrical Variability.

Thin insulating layers are used to modulate a depletion region at the source of a thin-film transistor. Bottom contact, staggered-electrode indium gallium zinc oxide transistors with a 3 nm Al2 O3 layer between the semiconductor and Ni source/drain contacts, show behaviors typical of source-gated transistors (SGTs): low saturation voltage (VD_SAT ≈ 3 V), change in VD_SAT with a gate voltage of only 0.12 V V-1 , and flat saturated output characteristics (small dependence of drain current on drain voltage). The transistors show high tolerance to geometry: the saturated current changes only 0.15× for 2-50 µm channels and 2× for 9-45 µm source-gate overlaps. A higher than expected (5×) increase in drain current for a 30 K change in temperature, similar to Schottky-contact SGTs, underlines a more complex device operation than previously theorized. Optimization for increasing intrinsic gain and reducing temperature effects is discussed. These devices complete the portfolio of contact-controlled transistors, comprising devices with Schottky contacts, bulk barrier, or heterojunctions, and now, tunneling insulating layers. The findings should also apply to nanowire transistors, leading to new low-power, robust design approaches as large-scale fabrication techniques with sub-nanometer control mature.

High-resistivity metal-oxide films through an interlayer of graphene grown directly on copper electrodes.

Functional oxides are important materials for multiple applications in flexible and transparent electronics. Electrically contacting these oxides to form active channels is often challenging as they suffer significant alteration or instabilities when interfaced with metal electrodes. Here, we demonstrate a new scheme to electrically contact thin films of semiconducting zinc tin oxide (ZnSnO) that employs pre-patterned copper electrodes encapsulated by chemical-vapour-deposited graphene. Measurement of over more than 100 channels with varying geometry and nature of contact shows that the bulk resistivity of the ZnSnO channels with graphene/Cu composite is at least two orders of magnitude larger than the same films deposited directly on aluminium (Al) contacts. Moreover, the ZnSnO channels with Cu/graphene contacts showed nearly ohmic transport, in contrast to space-charge-limited conduction observed for other contacting schemes. Our results outline a new application of graphene in a step towards the development of alternative contacting strategies for oxide electronics.

Split resonances for simultaneous detection and control measurements in a single bulk acoustic wave (BAW) sensor.

A self-referenced resonator consisting of two distinct areas of the top electrode made from Mo and a thin (5-30 nm) functional Au layer is shown. The fundamental frequencies for both the shear (∼1 GHz) and longitudinal (∼2 GHz) modes are split in two, such that mass attachment on the functional layer region causes frequency shifts in only one of the resonances, allowing a new approach of using the difference between the two frequencies to be used to measure mass attachment; this reduces the importance of device-to-device variability in absolute resonant frequency as a result of device fabrication.

Film bulk acoustic resonators (FBARs) as biosensors: A review.

Biosensors play important roles in different applications such as medical diagnostics, environmental monitoring, food safety, and the study of biomolecular interactions. Highly sensitive, label-free and disposable biosensors are particularly desired for many clinical applications. In the past decade, film bulk acoustic resonators (FBARs) have been developed as biosensors because of their high resonant frequency and small base mass (hence greater sensitivity), lower cost, label-free capability and small size. This paper reviews the piezoelectric materials used for FBARs, the optimisation of device structures, and their applications as biosensors in a wide range of biological applications such as the detection of antigens, DNAs and small biomolecules. Their integration with microfluidic devices and high-throughput detection are also discussed.

Analysis of the Conduction Mechanism and Copper Vacancy Density in p-type Cu2O Thin Films.

A quantitative and analytical investigation on the conduction mechanism in p-type cuprous oxide (Cu2O) thin films is performed based on analysis of the relative dominance of trap-limited and grain-boundary-limited conduction. It is found that carrier transport in as-deposited Cu2O is governed by grain-boundary-limited conduction (GLC), while after high-temperature annealing, GLC becomes insignificant and trap-limited conduction (TLC) dominates. This suggests that the very low Hall mobility of as-deposited Cu2O is due to significant GLC, and the Hall mobility enhancement by high-temperature annealing is determined by TLC. Evaluation of the grain size and the energy barrier height at the grain boundary shows an increase in the grain size and a considerable decrease in the energy barrier height after high-temperature annealing, which is considered to be the cause of the significant reduction in the GLC effect. Additionally, the density of copper vacancies was extracted; this quantitatively shows that an increase in annealing temperature leads to a reduction in copper vacancies.

Nanostructured plasmonic metapixels.

State-of-the-art pixels for high-resolution microdisplays utilize reflective surfaces on top of electrical backplanes. Each pixel is a single fixed color and will usually only modulate the amplitude of light. With the rise of nanophotonics, a pixel's relatively large surface area (~10 µm2), is in effect underutilized. Considering the unique optical phenomena associated with plasmonic nanostructures, the scope for use in reflective pixel technology for increased functionality is vast. Yet in general, low reflectance due to plasmonic losses, and sub-optimal design schemes, have limited the real-world application. Here we demonstrate the plasmonic metapixel; which permits high reflection capability whilst providing vivid, polarization switchable, wide color gamut filtering. Ultra-thin nanostructured metal-insulator-metal geometries result in the excitation of hybridized absorption modes across the visible spectrum. These modes include surface plasmons and quasi-guided modes, and by tailoring the absorption modes to exist either side of target wavelengths, we achieve pixels with polarization dependent multicolor reflection on mirror-like surfaces. Because the target wavelength is not part of a plasmonic process, subtractive color filtering and mirror-like reflection occurs. We demonstrate wide color-range pixels, RGB pixel designs, and in-plane Gaussian profile pixels that have the potential to enable new functionality beyond that of a conventional 'square' pixel.

Gravimetric sensors operating at 1.1 GHz based on inclined c-axis ZnO grown on textured Al electrodes.

Shear mode solidly mounted resonators (SMRs) are fabricated using an inclined c-axis ZnO grown on a rough Al electrode. The roughness of the Al surface is controlled by changing the substrate temperature during the deposition process to promote the growth of inclined ZnO microcrystals. The optimum substrate temperature to obtain homogeneously inclined c-axis grains in ZnO films is achieved by depositing Al at 100 °C with a surface roughness ~9.2 nm, which caused an inclination angle of ~25° of the ZnO c-axis with respect to the surface normal. Shear mode devices with quality-factors at resonance, Q r and effective electromechanical coupling factors, [Formula: see text], as high as 180 and 3.4% are respectively measured. Mass sensitivities, S m of (4.9 ± 0.1) kHz · cm2/ng and temperature coefficient of frequency (TCF) of ~-67 ppm/K are obtained using this shear mode. The performance of the devices as viscosity sensors and biosensors is demonstrated by determining the frequency shifts of water-ethanol mixtures and detection of Rabbit immunoglobin G (IgG) whole molecule (H&L) respectively.