Development of DNA-Based Lateral Flow Assay for Detection of LDLR Gene Mutation for Familial Hypercholesterolemia.

Background: The techniques for detecting single nucleotide polymorphisms (SNP) require lengthy and complex experimental procedures and expensive instruments that may only be available in some laboratories. Thus, a deoxyribonucleic acid (DNA)-based lateral flow assay (LFA) was developed as a point-of-care test (POCT) diagnostic tool for genotyping. In this study, single nucleotide variation (E101K) in the low-density lipoprotein receptor (LDLR) gene leading to familial hypercholesterolemia (FH) was chosen as a model. Methods: Hypercholesterolemic individuals (n = 103) were selected from the Malaysian Cohort project (UKM Medical Molecular Biology Institute) while the control samples were selected from the Biobank (UKM Medical Molecular Biology Institute). The DNA samples were isolated from whole blood. Polymerase chain reaction (PCR) amplification process was performed using bifunctional labelled primers specifically designed to correspond to the variant that differentiates wild-type and mutant DNA for visual detection on LFA. The variant was confirmed using Sanger sequencing, and the sensitivity and specificity of the LFA detection method were validated using the Agena MassARRAY® technique. Results: Out of 103 hypercholesterolemic individuals, 5 individuals (4.8%) tested positive for E101K, LDLR mutation and the rest, including healthy control individuals, tested negative. This result was concordant with Sanger sequencing and Agena MassARRAY®. These five individuals could be classified as Definite FH, as the DNA diagnosis was confirmed. The sensitivity and specificity of the variant detection by LFA is 100% compared to results using the genotyping method using Agena MassARRAY®. Conclusion: The developed LFA can potentially be used in the POC setting for detecting the E101K variant in the LDLR gene. This LFA can also be used to screen family members with E101K variant in the LDLR gene and is applicable for other SNP's detection.

Detection of SARS-CoV-2 in Environment: Current Surveillance and Effective Data Management of COVID-19.

Since diagnostic laboratories handle large COVID-19 samples, researchers have established laboratory-based assays and developed biosensor prototypes. Both share the same purpose; to ascertain the occurrence of air and surface contaminations by the SARS-CoV-2 virus. However, the biosensors further utilize internet-of-things (IoT) technology to monitor COVID-19 virus contamination, specifically in the diagnostic laboratory setting. The IoT-capable biosensors have great potential to monitor for possible virus contamination. Numerous studies have been done on COVID-19 virus air and surface contamination in the hospital setting. Through reviews, there are abundant reports on the viral transmission of SARS-CoV-2 through droplet infections, person-to-person close contact and fecal-oral transmission. However, studies on environmental conditions need to be better reported. Therefore, this review covers the detection of SARS-CoV-2 in airborne and wastewater samples using biosensors with comprehensive studies in methods and techniques of sampling and sensing (2020 until 2023). Furthermore, the review exposes sensing cases in public health settings. Then, the integration of data management together with biosensors is well explained. Last, the review ended with challenges to having a practical COVID-19 biosensor applied for environmental surveillance samples.

Role of Boron in Assisting the Super-Enhancement of Emissions from Carbon-Implanted Silicon.

The super enhancement of silicon band edge luminescence when co-implanted with boron and carbon is reported. The role of boron in the band edge emissions in silicon was investigated by deliberately introducing defects into the lattice structures. We aimed to increase the light emission intensity from silicon by boron implantation, leading to the formation of dislocation loops between the lattice structures. The silicon samples were doped with a high concentration of carbon before boron implantation and then annealed at a high temperature to activate the dopants into substitutional lattice sites. Photoluminescence (PL) measurements were performed to observe the emissions at the near-infrared region. The temperatures were varied from 10 K to 100 K to study the effect of temperature on the peak luminescence intensity. Two main peaks could be seen at ~1112 and 1170 nm by observing the PL spectra. The intensities shown by both peaks in the samples incorporated with boron are significantly higher than those in pristine silicon samples, and the highest intensity in the former was 600 times greater than that in the latter. Transmission electron microscopy (TEM) was used to study the structure of post-implant and post-anneal silicon sample. The dislocation loops were observed in the sample. Through a technique compatible with mature silicon processing technology, the results of this study will greatly contribute to the development of all Si-based photonic systems and quantum technologies.

Surface Acoustic Wave Propagation of GaN/Sapphire Integrated with a Gold Guiding Layer.

Gallium nitride (GaN), widely known as a wide bandgap semiconductor material, has been mostly employed in high power devices, light emitting diodes (LED), and optoelectronic applications. However, it could be exploited differently due to its piezoelectric properties, such as its higher SAW velocity and strong electromechanical coupling. In this study, we investigated the affect of the presence of a guiding layer made from titanium/gold on the surface acoustic wave propagation of the GaN/sapphire substrate. By fixing the minimum thickness of the guiding layer at 200 nm, we could observe a slight frequency shift compared to the sample without a guiding layer, with the presence of different types of surface mode waves (Rayleigh and Sezawa). This thin guiding layer could be efficient in transforming the propagation modes, acting as a sensing layer for the binding of biomolecules to the gold layer, and influencing the output signal in terms of frequency or velocity. The proposed GaN/sapphire device integrated with a guiding layer could possibly be used as a biosensor and in wireless telecommunication applications.

Kaedah Diagnostik Semasa dan Penggunaan Ujian Titik Penjagaan Pantas (POC) Bagi Mendiagnos Hiperkolesterolemia Famili (FH) (Current Diagnostic Techniques and the Use of Rapid Point-of-Care (POC) Testing to Diagnose Familial Hypercholesterolemia (FH)) / Jurnal Sains Kesihatan Malaysia

@#Familial hypercholesterolemia (FH) is an autosomal dominant inherited genetic disease characterized by increased concentrations of low-density lipoprotein (LDL-C) cholesterol in the blood. The risk of premature coronary heart disease in FH patients may increase without early treatment. Advancement in molecular biology techniques has enable early detection and diagnosis of FH. These techniques are cost-effective and have a shorter turnaround time. The current diagnostic tools available for FH diagnosis involving algorithm-based scoring criteria and various molecular diagnosis methods including next-generation sequencing (NGS), Sanger sequencing, Multiplex ligation-dependent probe amplification (MLPA) and DNA hybridisation assay are discussed in this review. However, molecular genetic testing is not widely available due to time-consuming procedures, high cost and requires trained personnel. Thus, this 36 review highlights the use of point of care (POC) testing as an approach to diagnose FH, particularly in countries lacking infrastructure and expertise in this field. Lateral flow testing (LFA) has gained attention as a POC diagnostic tool due to its simplicity, low cost and involved simple procedure and settings. The advantages of LFA made this technique a potential tool in addressing challenges in diagnosing FH, particularly for early diagnosis of family members.

Buffer Traps Effect on GaN-on-Si High-Electron-Mobility Transistor at Different Substrate Voltages.

Substrate voltage (VSUB) effects on GaN-on-Si high electron mobility transistors (HEMTs) power application performance with superlattice transition layer structure was investigated. The 2DEG conductivity and buffer stack charge redistribution can be affected by neutral/ionized donor and acceptor traps. As the donor/acceptor traps are excessively ionized or de-ionized by applying VSUB, the depletion region between the unintentionally doped (UID)/Carbon-doped (C-doped) GaN layer may exhibit a behavior similar to the p-n junction. An applied negative VSUB increases the concentration of both the ionized donor and acceptor traps, which increases the breakdown voltage (BV) by alleviating the non-uniform distribution of the vertical electric field. On the other hand, an applied positive VSUB causes the energy band bending flattener to refill the ionized traps and slightly improves the dynamic Ron degradation. Moreover, the amount of electrons injected into the buffer stack layer from the front side (2DEG channel/Ohmic contact) and the back side (AlN nucleation layer/superlattice transition layer) are asymmetric. Therefore, different VSUB can affect the conductivity of 2DEG through the field effect, buffer trapping effect, and charge redistribution, which can change the electrical performance of the device.

Transdermal Maltose-Based Microneedle Patch as Adjunct to Enhance Topical Anesthetic before Intravenous Cannulation of Pediatric Thalassemic Patients Receiving Blood Transfusion: A Randomized Controlled Trial Protocol.

Intravenous cannulation is experientially traumatic to children. To minimize this, EMLA® is applied on the would-be-cannulated area before IV cannula insertion. However, the time to achieve its maximum efficacy may be affected due to incomplete cutaneous absorption and the duration of application. The latter may be a limiting factor in a busy healthcare facility. The usage of dissolvable maltose microneedles may circumvent this problem by introducing micropores that will facilitate EMLA® absorption. A randomized phase II cross-over trial will be conducted to compare the Visual Analogue Scale (VAS) pain scores and skin conductance algesimeter index between 4 different interventions (1 fingertip unit (FTU) of EMLA® with microneedle patch for 30 min before cannulation; 0.5 FTU of EMLA® with microneedle patch for 30 min; 1 FTU of EMLA® with microneedle for 15 min; 1 FTU of EMLA® with sham patch for 30 min). A total of 26 pediatric patients with thalassemia aged between 6 and 18 years old and requiring blood transfusion will be recruited in this trial. During the visits, the VAS scores and skin conductance algesimeter index at venous cannulation will be obtained using the VAS rulers and PainMonitor™ machine, respectively. The trial will commence in August 2021 and is anticipated to end by August 2022.

Lifting the Veil: Characteristics, Clinical Significance, and Application of ß-2-Microglobulin as Biomarkers and Its Detection with Biosensors.

Because ß-2-microglobulin (ß2M) is a surface protein that is present on most nucleated cells, it plays a key role in the human immune system and the kidney glomeruli to regulate homeostasis. The primary clinical significance of ß2M is in dialysis-related amyloidosis, a complication of end-stage renal disease caused by a gradual accumulation of ß2M in the blood. Therefore, the function of ß2M in kidney-related diseases has been extensively studied to evaluate its glomerular and tubular functions. Because increased ß2M shedding due to rapid cell turnover may indicate other underlying medical conditions, the possibility to use ß2M as a versatile biomarker rose in prominence across multiple disciplines for various applications. Therefore, this work has reviewed the recent use of ß2M to detect various diseases and its progress as a biomarker. While the use of state-of-the-art ß2M detection requires sophisticated tools, high maintenance, and labor cost, this work also has reported the use of biosensor to quantify ß2M over the past decade. It is hoped that a portable and highly efficient ß2M biosensor device will soon be incorporated in point-of-care testing to provide safe, rapid, and reliable test results.

A Novel GaN:C Millimeter-Wave HEMT with AlGaN Electron-Blocking Layer.

An AlGaN/GaN/Si high electron mobility transistor (HEMT) using a GaN:C buffer with a 2 nm AlGaN electron-blocking layer (EBL) is investigated for the first time for millimeter-wave applications. Compared with the double heterostructure field effect transistor (DHFET), the AlGaN/GaN HEMT with the GaN:C/EBL buffer has a lower vertical leakage, higher thermal stability, and better RF performance. In addition, AlGaN EBL can prevent carbon-related traps from GaN:C and improve electron confinement in 2DEG during high-frequency operation. Finally, a Pout of 31.2 dBm with PAE of 21.7% were measured at 28 GHz at 28 V. These results demonstrated the great potential of HEMTs using GaN:C with AlGaN EBL epitaxy technology for millimeter-wave applications.

State-of-the-Art on Functional Titanium Dioxide-Integrated Nano-Hybrids in Electrical Biosensors.

Biosensors operating based on electrical methods are being accelerated toward rapid and efficient detection that improve the performance of the device. Continuous study in nano- and material-sciences has led to the inflection with properties of nanomaterials that fit the trend parallel to the biosensor evolution. Advancements in technology that focuses on nano-hybrid are being used to develop biosensors with better detection strategies. In this sense, titanium dioxide (TiO2) nanomaterials have attracted extensive interest in the construction of electrical biosensors. The formation of TiO2 nano-hybrid as an electrical transducing material has revealed good results with high performance. The modification of the sensing portion with a combination (nano-hybrid form) of nanomaterials has produced excellent sensors in terms of stability, reproducibility, and enhanced sensitivity. This review highlights recent research advancements with functional TiO2 nano-hybrid materials, and their victorious story in the construction of electrical biosensors are discussed. Future research directions with commercialization of these devices and their extensive utilizations are also discussed.

Potentials of MicroRNA in Early Detection of Ovarian Cancer by Analytical Electrical Biosensors.

The importance of nanotechnology in medical applications especially with biomedical sensing devices is undoubted. Several medical diagnostics have been developed by taking the advantage of nanomaterials, especially with electrical biosensors. Biosensors have been predominantly used for the quantification of different clinical biomarkers toward detection, screening, and follow-up the treatment. At present, ovarian cancer is one of the severe complications that cannot be identified until it becomes most dangerous as the advanced stage. Based on the American Cancer Society, 20% of cases involved in the detection of ovarian cancer are diagnosed at an early stage and 80% diagnosed at the later stages. The patient just has a common digestive problem and stomach ache as early symptoms and people used to ignore these symptoms. Micro ribonucleic acid (miRNA) is classified as small non-coding RNAs, their expressions change due to the association of cancer development and progression. This article reviews and discusses on the currently available strategies for the early detection of ovarian cancers using miRNA as a biomarker associated with electrical biosensors. A unique miRNA-based biomarker detections are specially highlighted with biosensor platforms to diagnose ovarian cancer.

Adoption of the Wet Surface Treatment Technique for the Improvement of Device Performance of Enhancement-Mode AlGaN/GaN MOSHEMTs for Millimeter-Wave Applications.

In this work, a low-power plasma oxidation surface treatment followed by Al2O3 gate dielectric deposition technique is adopted to improve device performance of the enhancement-mode (E-mode) AlGaN/GaN metal-oxide-semiconductor high-electron-mobility transistors (MOSHEMTs) intended for applications at millimeter-wave frequencies. The fabricated device exhibited a threshold voltage (Vth) of 0.13 V and a maximum transconductance (gm) of 484 (mS/mm). At 38 GHz, an output power density of 3.22 W/mm with a power-added efficiency (PAE) of 34.83% were achieved. Such superior performance was mainly attributed to the high-quality Al2O3 layer with a smooth surface which also suppressed the current collapse phenomenon.

Exploration of 2D Ti3C2 MXene for all solution processed piezoelectric nanogenerator applications.

A new 2D titanium carbide (Ti3C2), a low dimensional material of the MXene family has attracted remarkable interest in several electronic applications, but its unique structure and novel properties are still less explored in piezoelectric energy harvesters. Herein, a systematic study has been conducted to examine the role of Ti3C2 multilayers when it is incorporated in the piezoelectric polymer host. The 0.03 g/L of Ti3C2 has been identified as the most appropriate concentration to ensure the optimum performance of the fabricated device with a generated output voltage of about 6.0 V. The probable reasons might be due to the uniformity of nanofiller distribution in the polyvinylidene difluoride (PVDF) and the incorporation of Ti3C2 in a polymer matrix is found to enhance the ß-phase of PVDF and diminish the undesired α-phase configuration. Low tapping frequency and force were demonstrated to scavenge electrical energy from abundant mechanical energy resources particularly human motion and environmental stimuli. The fabricated device attained a power density of 14 µW.cm-2 at 10.8 MΩ of load resistor which is considerably high among 2D material-based piezoelectric nanogenerators. The device has also shown stable electrical performance for up to 4 weeks and is practically able to store energy in a capacitor and light up a LED. Hence, the Ti3C2-based piezoelectric nanogenerator suggests the potential to realize the energy harvesting application for low-power electronic devices.

Stress and Deformation of Optimally Shaped Silicon Microneedles for Transdermal Drug Delivery.

In this study, we demonstrated the fabrication of the concave conic shape microneedle with the aid of COMSOL Multiphysics simulation. The stress and buckling of the microneedle structure were simulated by applying various loads ranging from 50 to 800 g perpendiculars to the tip in order to predict the occurrence of microneedles structure deformation. The simulation study indicated that the surface buckling deformation does not occur to the microneedle structure with the increment of the load. The microneedles with dimensions of height and diameter tip ranging from 60 to 100 µm and 1 to 4 µm, respectively had been fabricated via an etching process in a mixture of hydrofluoric acid, nitric acid, and acetic acid. Three optimized microneedles but different in the structures were fabricated via the acidic etching process. The reproducibility of 3 different microneedle structures was 15, 20, and 60%, respectively. Stress and buckling analyses of the fabricated microneedles were further carried out on the rat skin. The obtained experimental results show promising applications for the deep dermis, stratum corneum to epidermis layer penetration.

Developing Conductive Highly Ordered Zinc Oxide Nanorods by Acetylacetonate-Assisted Growth.

Highly ordered vertically grown zinc oxide nanorods (ZnO NRs) were synthesized on ZnO-coated SiO2/Si substrate using zinc acetylacetonate hydrate as a precursor via a simple hydrothermal method at 85 °C. We used 0.05 M of ZnO solution to facilitate the growth of ZnO NRs and the immersion time was varied from 0.5 to 4 h. The atomic force microscopy revealed the surface roughness of ZnO seed layer used to grow the ZnO NRs. The morphology of vertically grown ZnO NRs was observed by field emission scanning electron microscopy. X-ray diffraction examination and transmission electron microscopy confirmed that the structure of highly ordered ZnO NRs was crystalline with a strong (002) peak corresponded to ZnO hexagonal wurtzite structure. The growth of highly ordered ZnO NRs was favorable due to the continuous supply of Zn2+ ions and chelating agents properties obtained from the acetylacetonate-derived precursor during the synthesis. Two-point probe current-voltage measurement and UV-vis spectroscopy of the ZnO NRs indicated a resistivity and optical bandgap value of 0.44 Ω.cm and 3.35 eV, respectively. The photoluminescence spectrum showed a broad peak centered at 623 nm in the visible region corresponded to the oxygen vacancies from the ZnO NRs. This study demonstrates that acetylacetonate-derived precursors can be used for the production of ZnO NRs-based devices with a potential application in biosensors.

Titanium dioxide-mediated resistive nanobiosensor for E. coli O157:H7.

A titanium dioxide nanoparticle (TiO2 NP)-mediated resistive biosensor is described for the determination of DNA fragments of Escherichia coli O157:H7 (E. coli O157:H7). The sol-gel method was used to synthesize the TiO2 NP, and microlithography was applied to fabricate the interdigitated sensor electrodes. Conventional E. coli DNA detections are facing difficulties in long-preparation-and-detection-time (more than 3 days). Hence, electronic biosensor was introduced by measuring the current-voltage (I-V) DNA probe without amplification of DNA fragments. The detection scheme is based on the interaction between the electron flow on the sensor and the introduction of negative charges from DNA probe and target DNA. The biosensor has a sensitivity of 1.67 × 1013 Ω/M and a wide analytical range. The limit detection is down to 1 × 10-11 M of DNA. The sensor possesses outstanding repeatability and reproducibility and is cabable to detect DNA within 15 min in a minute-volume sample (1 µL). Graphical abstract Fig. (a) Graphical illustration of electronic biosensor set up and (b) relationship between limit of detection (LOD) and the unaffected poultry samples on E. coli O157:H7.

Electrical transportation mechanisms of molybdenum disulfide flakes-graphene quantum dots heterostructure embedded in polyvinylidene fluoride polymer.

In the interest of the trend towards miniaturization of electronic gadgets, this study demonstrates a high-density data storage device with a very simple three-stacking layer consisting of only one charge trapping layer. A simple solution-processed technique has been used to fabricate the tristable non-volatile memory. The three-stacking layer was constructed in between two metals to form a two-terminal metal-insulator-metal structure. The fabricated device showed a large multilevel memory hysteresis window with a measured ON/OFF current ratio of 107 that might be attributed to the high charge trapped in molybdenum disulphide (MoS2) flakes-graphene quantum dots (GQDs) heterostructure. Transmission electron microscopy was performed to examine the orientation of MoS2-GQD and mixture dispersion preparation method. The obtained electrical data was used further to speculate the possible transport mechanisms through the fabricated device by a curve fitting technique. Also, endurance cycle and retention tests were performed at room temperature to investigate the stability of the device.

Solid-State Limited Nucleation of NiSi/SiC Core-Shell Nanowires by Hot-Wire Chemical Vapor Deposition.

This work demonstrated a growth of well-aligned NiSi/SiC core-shell nanowires by a one-step process of hot-wire chemical vapor deposition on Ni-coated crystal silicon substrates at different thicknesses. The NiSi nanoparticles (60 to 207 nm) acted as nano-templates to initially inducing the growth of these core-shell nanowires. These core-shell nanowires were structured by single crystalline NiSi and amorphous SiC as the cores and shells of the nanowires, respectively. It is proposed that the precipitation of the NiSi/SiC are followed according to the nucleation limited silicide reaction and the surface-migration respectively for these core-shell nanowires. The electrical performance of the grown NiSi/SiC core-shell nanowires was characterized by the conducting AFM and it is found that the measured conductivities of the nanowires were higher than the reported works that might be enhanced by SiC shell layer on NiSi nanowires. The high conductivity of NiSi/SiC core-shell nanowires could potentially improve the electrical performance of the nanowires-based devices for harsh environment applications such as field effect transistors, field emitters, space sensors, and electrochemical devices.

A Theoretical Study of Surface Mode Propagation with a Guiding Layer of GaN/Sapphire Hetero-Structure in Liquid Medium.

Gallium Nitride (GaN) is considered as the second most popular semiconductor material in industry after silicon. This is due to its wide applications encompassing Light Emitting Diode (LED) and power electronics. In addition, its piezoelectric properties are fascinating to be explored as electromechanical material for the development of diverse microelectromechanical systems (MEMS) application. In this article, we conducted a theoretical study concerning surface mode propagation, especially Rayleigh and Sezawa mode in the layered GaN/sapphire structure with the presence of various guiding layers. It is demonstrated that the increase in thickness of guiding layer will decrease the phase velocities of surface mode depending on the material properties of the layer. In addition, the Q-factor value indicating the resonance properties of surface mode appeared to be affected with the presence of fluid domain, particularly in the Rayleigh mode. Meanwhile, the peak for Sezawa mode shows the highest Q factor and is not altered by the presence of fluid. Based on these theoretical results using the finite element method, it could contribute to the development of a GaN-based device to generate surface acoustic wave, especially in Sezawa mode which could be useful in acoustophoresis, lab on-chip and microfluidics applications.

Curvature contribution on anodic aluminium oxide pore formation: a detailed analytical study.

Anodic aluminium oxide (AAO) is a self-organised nanopore that has been widely studied due to the ease of its synthesization and pore properties manipulation. However, pore growth behaviour under different geometrical surfaces is rarely studied, particularly on the effect of combined curved surfaces towards pore growth properties, which is crucial in designing unique porous platform for specific applications. This paper reports study on the decisive effect of curvature surfaces on development of pore structure and properties at a constant potential. In this work, AAO grown on treated convex and concave surfaces were analysed in terms of pore quantity, pore diameter, interpore distance, pore length and other parameters of pore bottom geometry in conjugation with observation of pore cessation, bifurcation, bending and tapering. The unique formation of tapered pore was observed and described. Major factors deciding pore properties under curved surfaces were identified and discussed. We introduced a new parameter for surface quantification known as central inscribed angle, which was identified to be the central factor which decides pore growth behaviour under a curvature. Here, we observed a different trend in growth rate of pores under different curvatures, which oppose the commonly accepted convex > planar > concave pattern. Levelling height was later identified to be the decisive factor in determining growth rate of pores under a curvature at different geometrical location. These findings open up possibility to precisely control and tailor the growing path and pore structures of AAO simply via anodising an Al sheet under combined curvature surfaces, which could be beneficial for future novel applications.