Biosensing based on surface-enhanced Raman spectroscopy as an emerging/next-generation point-of-care approach for acute myocardial infarction diagnosis.

Cardiovascular disease is a major global health issue. In particular, acute myocardial infarction (AMI) requires urgent attention and early diagnosis. The use of point-of-care diagnostics has resulted in the improved management of cardiovascular disease, but a major drawback is that the performance of POC devices does not rival that of central laboratory tests. Recently, many studies and advances have been made in the field of surface-enhanced Raman scattering (SERS), including the development of POC biosensors that utilize this detection method. Here, we present a review of the strengths and limitations of these emerging SERS-based biosensors for AMI diagnosis. The ability of SERS to multiplex sensing against existing POC detection methods are compared and discussed. Furthermore, SERS calibration-free methods that have recently been explored to minimize the inconvenience and eliminate the limitations caused by the limited linear range and interassay differences found in the calibration curves are outlined. In addition, the incorporation of artificial intelligence (AI) in SERS techniques to promote multivariate analysis and enhance diagnostic accuracy are discussed. The future prospects for SERS-based POC devices that include wearable POC SERS devices toward predictive, personalized medicine following the Fourth Industrial Revolution are proposed.

Distinct Lipid Phenotype of Cancer-Associated Fibroblasts (CAFs) Isolated From Overweight/Obese Endometrial Cancer Patients as Assessed Using Raman Spectroscopy.

Obesity is strongly linked with increased risk and poorer prognosis of endometrial cancer (EC). Cancer-associated fibroblasts (CAFs) are activated fibroblasts that form a large component of the tumor microenvironment and undergo metabolic reprogramming to provide critical metabolites for tumor growth. However, it is still unknown how obesity, characterized by a surplus of free fatty acids drives the modifications of CAFs lipid metabolism which may provide the mechanistic link between obesity and EC progression. The present study aims to evaluate the utility of Raman spectroscopy, an emerging nondestructive analytical tool to detect signature changes in lipid metabolites of CAFs from EC patients with varying body mass index. We established primary cultures of fibroblasts from human EC tissues, and CAFs of overweight/obese and nonobese women using antibody-conjugated magnetic beads isolation. These homogeneous fibroblast cultures expressed fibroblast markers, including α-smooth muscle actin and vimentin. Analysis was made in the Raman spectra region best associated with cancer progression biochemical changes in lipids (600-1800 cm-1 and 2800-3200 cm-1). Direct band analysis and ratiometric analysis were conducted to extract information from the Raman spectrum. Present results demonstrated minor shifts in the CH2 symmetric stretch of lipids at 2879 cm-1 and CH3 asymmetric stretching from protein at 2932 cm-1 in the overweight/obese CAFS compared to nonobese CAFs, indicating increased lipid content and a higher degree of lipid saturation. Principal component analysis showed that CAFs from overweight/obese and nonobese EC patients can be clearly distinguished indicating the capability of Raman spectroscopy to detect changes in biochemical components. Our results suggest Raman spectroscopy supported by chemometric analysis is a reliable technique for characterizing metabolic changes in clinical samples, providing an insight into obesity-driven alteration in CAFs, a critical stromal component during EC tumorigenesis.

Molybdenum Disulfide Nanosheets Decorated with Platinum Nanoparticle as a High Active Electrocatalyst in Hydrogen Evolution Reaction.

Electrochemical hydrogen evolution reaction (HER) refers to the process of generating hydrogen by splitting water molecules with applied external voltage on the active catalysts. HER reaction in the acidic medium can be studied by different mechanisms such as Volmer reaction (adsorption), Heyrovsky reaction (electrochemical desorption) or Tafel reaction (recombination). In this paper, facile hydrothermal methods are utilized to synthesis a high-performance metal-inorganic composite electrocatalyst, consisting of platinum nanoparticles (Pt) and molybdenum disulfide nanosheets (MoS2) with different platinum loading. The as-synthesized composite is further used as an electrocatalyst for HER. The as-synthesized Pt/Mo-90-modified glassy carbon electrode shows the best electrocatalytic performance than pure MoS2 nanosheets. It exhibits Pt-like performance with the lowest Tafel slope of 41 mV dec-1 and superior electrocatalytic stability in an acidic medium. According to this, the HER mechanism is related to the Volmer-Heyrovsky mechanism, where hydrogen adsorption and desorption occur in the two-step process. According to electrochemical impedance spectroscopy analysis, the presence of Pt nanoparticles enhanced the HER performance of the MoS2 nanosheets because of the increased number of charge carriers transport.

Heteroepitaxial Growth of an Ultrathin ß-Ga2O3 Film on a Sapphire Substrate Using Mist CVD with Fluid Flow Modeling.

ß-Gallium oxide (Ga2O3) has received intensive attention in the scientific community as a significant high-power switching semiconductor material because of its remarkable intrinsic physical characteristics and growth stability. This work reports the heteroepitaxial growth of the ß-Ga2O3 ultrathin film on a sapphire substrate via mist chemical vapor deposition (CVD). This study used a simple solution-processed and nonvacuum mist CVD method to grow a heteroepitaxial ß-Ga2O3 thin film at 700 °C using a Ga precursor and carrier gases such as argon and oxygen. Various characterization techniques were used to determine the properties of the thin film. Additionally, a computational study was performed to study the temperature distribution and different mist velocity profiles of the finite element mist CVD model. This simulation study is essential for investigating low to high mist velocities over the substrate and applying low velocity to carry out experimental work. XRD and AFM results show that the ß-Ga2O3 thin film is grown on a sapphire substrate of polycrystalline nature with a smooth surface. HR-TEM measurement and UV-visible transmission spectrometry demonstrated heteroepitaxial ß-Ga2O3 in an ultrathin film with a band gap of 4.8 eV.

Temperature Dependence of Ultrathin Mixed-Phase Ga2O3 Films Grown on the α-Al2O3 Substrate via Mist-CVD.

Alpha (α)- and beta (ß)-phase gallium oxide (Ga2O3), emerging as ultrawide-band gap semiconductors, have been paid a great deal of attention in optoelectronics and high-performance power semiconductor devices owing to their ultrawide band gap ranging from 4.4 to 5.3 eV. The hot-wall mist chemical vapor deposition (mist-CVD) method has been shown to be effective for the growth of pure α- and ß-phase Ga2O3 thin films on the α-Al2O3 substrate. However, challenges to preserve their intrinsic properties at a critical growth temperature for robust applications still remain a concern. Here, we report a convenient route to grow a mixed α- and ß-phase Ga2O3 ultrathin film on the α-Al2O3 substrate via mist-CVD using a mixture of the gallium precursor and oxygen gas at growth temperatures, ranging from 470 to 700 °C. The influence of growth temperature on the film characteristics was systematically investigated. The results revealed that the as-grown Ga2O3 film possesses a mixed α- and ß-phase with an average value of dislocation density of 1010 cm-2 for all growth temperatures, indicating a high lattice mismatch between the film and the substrate. At 600 °C, the ultrathin and smooth Ga2O3 film exhibited a good surface roughness of 1.84 nm and an excellent optical band gap of 5.2 eV. The results here suggest that the mixed α- and ß-phase Ga2O3 ultrathin film can have great potential in developing future high-power electronic devices.

Chitosan-Coated-PLGA Nanoparticles Enhance the Antitumor and Antimigration Activity of Stattic - A STAT3 Dimerization Blocker.

PURPOSE: The use of nanocarriers to improve the delivery and efficacy of antimetastatic agents is less explored when compared to cytotoxic agents. This study reports the entrapment of an antimetastatic Signal Transducer and Activator of Transcription 3 (STAT3) dimerization blocker, Stattic (S) into a chitosan-coated-poly(lactic-co-glycolic acid) (C-PLGA) nanocarrier and the improvement on the drug's physicochemical, in vitro and in vivo antimetastatic properties post entrapment. METHODS: In vitro, physicochemical properties of the Stattic-entrapped C-PLGA nanoparticles (S@C-PLGA) and Stattic-entrapped PLGA nanoparticles (S@PLGA, control) in terms of size, zeta potential, polydispersity index, drug loading, entrapment efficiency, Stattic release in different medium and cytotoxicity were firstly evaluated. The in vitro antimigration properties of the nanoparticles on breast cancer cell lines were then studied by Scratch assay and Transwell assay. Study on the in vivo antitumor efficacy and antimetastatic properties of S@C-PLGA compared to Stattic were then performed on 4T1 tumor bearing mice. RESULTS: The S@C-PLGA nanoparticles (141.8 ± 2.3 nm) was hemocompatible and exhibited low Stattic release (12%) in plasma. S@C-PLGA also exhibited enhanced in vitro anti-cell migration potency (by >10-fold in MDA-MB-231 and 5-fold in 4T1 cells) and in vivo tumor growth suppression (by 33.6%) in 4T1 murine metastatic mammary tumor bearing mice when compared to that of the Stattic-treated group. Interestingly, the number of lung and liver metastatic foci was found to reduce by 50% and 56.6%, respectively, and the average size of the lung metastatic foci was reduced by 75.4% in 4T1 tumor-bearing mice treated with S@C-PLGA compared to Stattic-treated group (p < 0.001). CONCLUSION: These findings suggest the usage of C-PLGA nanocarrier to improve the delivery and efficacy of antimetastatic agents, such as Stattic, in cancer therapy.

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.

Using SERS-based microfluidic paper-based device (µPAD) for calibration-free quantitative measurement of AMI cardiac biomarkers.

Recently, surface enhanced Raman scattering (SERS) has attracted much attention in medical diagnosis applications owing to better detection sensitivity and lower limit of detection (LOD) than colorimetric detection. In this paper, a novel calibration-free SERS-based µPAD with multi-reaction zones for simultaneous quantitative detection of multiple cardiac biomarkers - GPBB, CK-MB and cTnT for early diagnosis and prognosis of acute myocardial infarction (AMI) are presented. Three distinct Raman probes were synthesised, subsequently conjugated with respective detecting antibodies and used as SERS nanotags for cardiac biomarker detection. Using a conventional calibration curve, quantitative simultaneous measurement of multiple cardiac biomarkers on SERS-based µPAD was performed based on the characteristic Raman spectral features of each reporter used in different nanotags. However, a calibration free point-of-care testing device is required for fast screening to rule-in and rule-out AMI patients. Partial least squares predictive models were developed and incorporated into the immunosensing system, to accurately quantify the three unknown cardiac biomarkers levels in serum based on the previously obtained Raman spectral data. This method allows absolute quantitative measurement when conventional calibration curve fails to provide accurate estimation of cardiac biomarkers, especially at low and high concentration ranges. Under an optimised condition, the LOD of our SERS-based µPAD was identified at 8, 10, and 1 pg mL-1, for GPBB, CK-MB and cTnT, respectively, which is well below the clinical cutoff values. Therefore, this proof-of-concept technique shows significant potential for highly sensitive quantitative detection of multiplex cardiac biomarkers in human serum to expedite medical decisions for enhanced patient care.

Bi-doping improves the magnetic properties of zinc oxide nanowires.

Room-temperature ferromagnetism in the large and direct bandgap diluted magnetic semiconductor zinc oxide (ZnO) is attributed to the intrinsic defects and p-orbital-p-orbital (p-p) coupling interaction. However, due to oxidation, the ferromagnetism induced by defects is unstable. In the present work, the solution process synthesis route was utilized to grow pristine and bismuth-doped, highly crystalline ZnO nanowire (ZnO NW)-based samples. The FE-SEM images showed that the grown ZnO NWs have a preferred orientation along the c-axis in the (001) direction due to the anisotropic crystal nature of ZnO. X-ray photoelectron spectroscopy (XPS) confirmed the presence of Bi, and at a higher doping content, the bismuth oxide phase appeared. The XRD patterns showed the wurtzite crystal structure, and the large intensity of the (002) peak suggests that most of the reflection was from the top hexagonal face of the NWs, and thus, the wires are predominantly aligned along the c-axis. The TEM analysis further confirmed the crystal growth direction along the (001) direction. The UV-Visible absorption and PL measurements also showed a decrease in the bandgap with an increase in doping concentration, which may be associated with the sp-d exchange interaction between the localized d-electrons and band electrons of the Bi ions. Bi-doping tended to increase the PL intensity in the visible region. The magnetic properties measured by SQUID at 4 and 300 K showed ferromagnetic behaviour for both the pristine and Bi-doped samples. However, the saturation magnetization for the Bi-doped samples was higher compared to that of the pristine ZnO samples until the threshold doping value. The obtained results demonstrated that Bi-doping can be used to tune both the optical and magnetic properties of ZnO NWs, hence paving the way for future spintronics and spin-polarized optoelectronics applications.

Paper microfluidic device for early diagnosis and prognosis of acute myocardial infarction via quantitative multiplex cardiac biomarker detection.

The early detection of acute myocardial infarction (AMI) upon the onset of chest pain symptoms is crucial for patient survival. However, this detection is challenging, particularly without a persistent elevation of ST-segment reflected in an electrocardiogram or in blood tests. A majority of the available point-of-care testing devices allow accurate and rapid diagnosis of AMI. However, AMI diagnosis is reliable only at intermediate and later stages, with myocardial injury (> 6 h) and MI, based on the expression of specific cardiac biomarkers including troponin I or T (cTnI or cTnT), creatine kinase-MB (CK-MB), and myoglobin. Diagnosis at the early myocardial ischemia stage is not possible. To overcome this limitation, a sensitive and rapid microfluidic paper-based device (µPAD) was developed for the simultaneous detection of multiple cardiac biomarkers for the early and late diagnosis of AMI. The glycogen phosphorylase isoenzyme BB (GPBB) was detected during early (within first 4 h) ischemic myocardial injury. On the same µPAD platform, detection of prolonged elevation of levels of cTnT and CK-MB, which are only produced 6 h after the onset of chest pain in human serum, was possible. Sandwich immunoassay performed on the µPAD achieved reproducibility (RSD approximately 10% and intra-and inter-day precision (CV 10-20%, 99th percentile), as well as consistently stable test results for 28 days, with strong correlation (r2= 0.962), using the standard Siemens Centaur XPT Immunoassay system. The present findings indicate the potential of the µPAD platform as a point-of-care device for the early diagnosis and prognosis of AMI.

Molybdenum disulfide nanosheet decorated with silver nanoparticles for selective detection of dopamine.

A metal-inorganic composite, comprises of silver-molybdenum disulfide nanosheets (Ag@MoS2) was synthesized at low temperature. The Ag@MoS2 composite was drop-casted onto a glassy carbon electrode (GCE) for a highly selective dopamine (DA) detection in the presence of interfering compounds such as uric acid (UA) and ascorbic acid (AA). The physicochemical analysis of the nanosheets was carried out with X-ray diffraction, transmission electron microscopy and X-ray photoelectron spectroscopy. The as-prepared Ag@MoS2-modified GCE displayed excellent electrocatalytic activity toward DA oxidation, with a 0.2 µM detection limit at a signal-to-noise ratio of 3 and an extensive linear detection range from 1 µM to 500 µM (R2 = 0.9983). The fabricated non-enzymatic electrochemical sensor demonstrated superior selectivity and stability for the detection of DA with the removal of AA and UA interfering compounds.

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.

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.

Microfluidic paper-based analytical devices for potential use in quantitative and direct detection of disease biomarkers in clinical analysis.

Clinicians, working in the health-care diagnostic systems of developing countries, currently face the challenges of rising costs, increased number of patient visits, and limited resources. A significant trend is using low-cost substrates to develop microfluidic devices for diagnostic purposes. Various fabrication techniques, materials, and detection methods have been explored to develop these devices. Microfluidic paper-based analytical devices (µPADs) have gained attention for sensing multiplex analytes, confirming diagnostic test results, rapid sample analysis, and reducing the volume of samples and analytical reagents. µPADs, which can provide accurate and reliable direct measurement without sample pretreatment, can reduce patient medical burden and yield rapid test results, aiding physicians in choosing appropriate treatment. The objectives of this review are to provide an overview of the strategies used for developing paper-based sensors with enhanced analytical performances and to discuss the current challenges, limitations, advantages, disadvantages, and future prospects of paper-based microfluidic platforms in clinical diagnostics. µPADs, with validated and justified analytical performances, can potentially improve the quality of life by providing inexpensive, rapid, portable, biodegradable, and reliable diagnostics.

Controlled growth of Si-based heterostructure nanowires and their structural and electrical properties.

Ni-catalyzed Si-based heterostructure nanowires grown on crystal Si substrates by hot-wire chemical vapor deposition (HWCVD) were studied. The nanowires which included NiSi nanowires, NiSi/Si core-shell nanowires, and NiSi/SiC core-shell nanowires were grown by varying the filament temperature T f from 1150 to 1850 °C. At a T f of 1450 °C, the heterostructure nanowires were formed by crystalline NiSi and crystalline Si that were attributed to the core and shell of the nanowires, respectively. The morphology of the nanowires showed significant changes with the increase in the filament temperature to 1850 °C. Moreover, the effect of hydrogen heat transfer from the filament temperature demonstrated significant phase changes from NiSi to Ni2Si with increase in the filament temperature. The increased filament temperature also enhanced reactions in the gas phase thus generating more SiC clusters and consequently formed the NiSi/SiC heterostructure core-shell nanowires at T f of 1850 °C. This paper discusses the role of filament temperatures on the growth and constituted phase change of the nanowires as well as their electrical characteristics.