Progress in nanoparticle-based electrochemical biosensors for hormone detection.

Hormones are chemical messengers that regulate a wide range of physiological processes including metabolism, development, growth, reproduction and mood. The concentration of hormones that orchestrate the numerous bodily functions is very low (1 nM or less). Efforts have been made to develop highly sensitive tools to detect them. This review represents a critical comparison between different types of nanoparticle-based electrochemical biosensors for the detection of various hormones, namely cortisol, sex hormones (estradiol, progesterone, testosterone), insulin, thyroid-stimulating hormone (TSH) and growth hormone (GH). The electrochemical biosensors investigated for each hormone are first divided on the basis of the biological fluid tested for their detection, and successively on the basis of the electrochemical transducer utilized in the device (voltammetric or impedimetric). Focus is placed on the nanoparticles employed and the successive electrode modification developed in order to improve detection sensitivity and specificity and biosensor stability. Limit of detection (LOD), linear range, reproducibility and possibility of regeneration for continuous reuse are also investigated and compared. The review also addresses the recent trends in the development of wearable biosensors and point-of-care testing for hormone detection in clinical diagnostics useful for endocrinology research, and the future perspectives regarding the integration of nanomaterials, microfluidics, near field communication (NFC) technology and portable devices.

Magnetic iron oxide nanogels for combined hyperthermia and drug delivery for cancer treatment.

Hyperthermia and chemotherapy represent potential modalities for cancer treatments. However, hyperthermia can be invasive, while chemotherapy drugs often have severe side effects. Recent clinical investigations have underscored the potential synergistic efficacy of combining hyperthermia with chemotherapy, leading to enhanced cancer cell killing. In this context, magnetic iron oxide nanogels have emerged as promising candidates as they can integrate superparamagnetic iron oxide nanoparticles (IONPs), providing the requisite magnetism for magnetic hyperthermia, with the nanogel scaffold facilitating smart drug delivery. This review provides an overview of the synthetic methodologies employed in fabricating magnetic nanogels. Key properties and designs of these nanogels are discussed and challenges for their translation to the clinic and the market are summarised.

Development of a thermochromic lateral flow assay to improve sensitivity for dengue virus serotype 2 NS1 detection.

Dengue disease is a viral infection that has been widespread in tropical regions, such as Southeast Asia, South Asia and South America. A worldwide effort has been made over a few decades to halt the spread of the disease and reduce fatalities. Lateral flow assay (LFA), a paper-based technology, is used for dengue virus detection and identification because of its simplicity, low cost and fast response. However, the sensitivity of LFA is relatively low and is usually insufficient to meet the minimum requirement for early detection. In this study, we developed a colorimetric thermal sensing LFA format for the detection of dengue virus NS1 using recombinant dengue virus serotype 2 NS1 protein (DENV2-NS1) as a model antigen. Plasmonic gold nanoparticles, including gold nanospheres (AuNSPs) and gold nanorods (AuNRs), and magnetic nanoparticles (MNPs), namely iron oxide nanoparticles (IONPs) and zinc ferrite nanoparticles (ZFNPs), were studied for their thermal properties for sensing assays. AuNSPs with 12 nm diameter were chosen due to their great photothermal effect against light-emitting diodes (LEDs). In the thermal sensing assay, a thermochromic sheet is used as a temperature sensor transforming heat into a visible colour. In the typical LFA, the test line is visible at 6.25 ng mL-1 while our thermal sensing LFA offers a visual signal that can be observed at as low as 1.56 ng mL-1. The colorimetric thermal sensing LFA is capable of reducing the limit of detection (LOD) of DENV2-NS1 by 4 times compared to the typical visual readout. The colorimetric thermal sensing LFA can enhance the sensitivity of detection and deliver visuality to the user to translate without the need for an infrared (IR) camera. It has the potential to expand the utilities of LFA and satisfy early diagnostic applications.

A Genetic Algorithm for Universal Optimization of Ultrasensitive Surface Plasmon Resonance Sensors with 2D Materials.

We present a general optimization technique for surface plasmon resonance, (SPR) yielding a range of ultrasensitive SPR sensors from a materials database with an enhancement of ∼100%. Applying the algorithm, we propose and demonstrate a novel dual-mode SPR structure coupling SPP and a waveguide mode within GeO2 featuring an anticrossing behavior and an unprecedented sensitivity of 1364 deg/RIU. An SPR sensor operating at wavelengths of 633 nm having a bimetal Al/Ag structure sandwiched between hBN can achieve a sensitivity of 578 deg/RIU. For a wavelength of 785 nm, we optimized a sensor as a Ag layer sandwiched between hBN/MoS2/hBN heterostructures achieving a sensitivity of 676 deg/RIU. Our work provides a guideline and general technique for the design and optimization of high sensitivity SPR sensors for various sensing applications in the future.

Greatly Enhanced Resonant Exciton-Trion Conversion in Electrically Modulated Atomically Thin WS2 at Room Temperature.

Excitonic resonance in atomically thin semiconductors offers a favorite platform to study 2D nanophotonics in both classical and quantum regimes and promises potentials for highly tunable and ultra-compact optical devices. The understanding of charge density dependent exciton-trion conversion is the key for revealing the underlaying physics of optical tunability. Nevertheless, the insufficient and inefficient light-matter interactions hinder the observation of trionic phenomenon and the development of excitonic devices for dynamic power-efficient electro-optical applications. Here, by engaging an optical cavity with atomically thin transition metal dichalcogenides (TMDCs), greatly enhanced exciton-trion conversion is demonstrated at room temperature (RT) and achieve electrical modulation of reflectivity of ≈40% at exciton and 7% at trion state, which correspondingly enables a broadband large phase tuning in monolayer tungsten disulfide. Besides the absorptive conversion, ≈100% photoluminescence conversion from excitons to trions is observed at RT, illustrating a clear physical mechanism of an efficient exciton-trion conversion for extraordinary optical performance. The results indicate that both excitons and trions can play significant roles in electrical modulation of the optical parameters of TMDCs at RT. The work shows the real possibility for realizing electrical tunable and multi-functional ultra-thin optical devices using 2D materials.

Zn doped iron oxide nanoparticles with high magnetization and photothermal efficiency for cancer treatment.

Magnetic nanoparticles (NPs) are powerful agents to induce hyperthermia in tumours upon the application of an alternating magnetic field or an infrared laser. Dopants have been investigated to alter different properties of materials. Herein, the effect of zinc doping into iron oxide NPs on their magnetic properties and structural characteristics has been investigated in-depth. A high temperature reaction with autogenous pressure was used to prepare iron oxide and zinc ferrite NPs of same size and morphology for direct comparison. Pressure was key in obtaining high quality nanocrystals with reduced lattice strain (27% less) and enhanced magnetic properties. Zn0.4Fe2.6O4 NPs with small size of 10.2 ± 2.5 nm and very high saturation magnetisation of 142 ± 9 emu gFe+Zn-1 were obtained. Aqueous dispersion of the NPs showed long term magnetic (up to 24 months) and colloidal stability (at least 6 d) at physiologically mimicking conditions. The samples had been kept in the fridge and had been stable for four years. The biocompatibility of Zn0.4Fe2.6O4 NPs was next evaluated by metabolic activity, membrane integrity and clonogenic assays, which show an equivalence to that of iron oxide NPs. Zinc doping decreased the bandgap of the material by 22% making it a more efficient photothermal agent than iron oxide-based ones. Semiconductor photo-hyperthermia was shown to outperform magneto-hyperthermia in cancer cells, reaching the same temperature 17 times faster whilst using 20 times less material (20 mgFe+Zn ml-1vs. 1 mgFe+Zn ml-1). Magnetothermal conversion was minimally hindered in the cellular confinement whilst photothermal efficiency remained unchanged. Photothermia treatment alone achieved 100% cell death after 10 min of treatment compared to only 30% cell death achieved with magnetothermia at clinically relevant settings for each at their best performing concentration. Altogether, these results suggest that the biocompatible and superparamagnetic zinc ferrite NPs could be a next biomaterial of choice for photo-hyperthermia, which could outperform current iron oxide NPs for magnetic hyperthermia.

A versatile non-fouling multi-step flow reactor platform: demonstration for partial oxidation synthesis of iron oxide nanoparticles.

In the last decade flow reactors for material synthesis were firmly established, demonstrating advantageous operating conditions, reproducible and scalable production via continuous operation, as well as high-throughput screening of synthetic conditions. Reactor fouling, however, often restricts flow chemistry and the common fouling prevention via segmented flow comes at the cost of inflexibility. Often, the difficulty of feeding reagents into liquid segments (droplets or slugs) constrains flow syntheses using segmented flow to simple synthetic protocols with a single reagent addition step prior or during segmentation. Hence, the translation of fouling prone syntheses requiring multiple reagent addition steps into flow remains challenging. This work presents a modular flow reactor platform overcoming this bottleneck by fully exploiting the potential of three-phase (gas-liquid-liquid) segmented flow to supply reagents after segmentation, hence facilitating fouling free multi-step flow syntheses. The reactor design and materials selection address the operation challenges inherent to gas-liquid-liquid flow and reagent addition into segments allowing for a wide range of flow rates, flow ratios, temperatures, and use of continuous phases (no perfluorinated solvents needed). This "Lego®-like" reactor platform comprises elements for three-phase segmentation and sequential reagent addition into fluid segments, as well as temperature-controlled residence time modules that offer the flexibility required to translate even complex nanomaterial synthesis protocols to flow. To demonstrate the platform's versatility, we chose a fouling prone multi-step synthesis, i.e., a water-based partial oxidation synthesis of iron oxide nanoparticles. This synthesis required I) the precipitation of ferrous hydroxides, II) the addition of an oxidation agent, III) a temperature treatment to initiate magnetite/maghemite formation, and IV) the addition of citric acid to increase the colloidal stability. The platform facilitated the synthesis of colloidally stable magnetic nanoparticles reproducibly at well-controlled synthetic conditions and prevented fouling using heptane as continuous phase. The biocompatible particles showed excellent heating abilities in alternating magnetic fields (ILP values >3 nH m2 kgFe-1), hence, their potential for magnetic hyperthermia cancer treatment. The platform allowed for long term operation, as well as screening of synthetic conditions to tune particle properties. This was demonstrated via the addition of tetraethylenepentamine, confirming its potential to control particle morphology. Such a versatile reactor platform makes it possible to translate even complex syntheses into flow, opening up new opportunities for material synthesis.

Penicillium digitatum as a Model Fungus for Detecting Antifungal Activity of Botanicals: An Evaluation on Vietnamese Medicinal Plant Extracts.

Medicinal plants play important roles in traditional medicine, and numerous compounds among them have been recognized for their antimicrobial activity. However, little is known about the potential of Vietnamese medicinal plants for antifungal activity. In this study, we examined the antagonistic activity of twelve medicinal plant species collected in Northern Vietnam against Penicillium digitatum, Aspergillus flavus, Aspergillus fumigatus, and Candida albicans. The results showed that the antifungal activities of the crude extracts from Mahonia bealei, Ficus semicordata, and Gnetum montanum were clearly detected with the citrus postharvest pathogen P. digitatum. These extracts could fully inhibit the growth of P. digitatum on the agar medium, and on the infected citrus fruits at concentrations of 300-1000 µg/mL. Meanwhile, the other tested fungi were less sensitive to the antagonistic activity of the plant extracts. In particular, we found that the ethanolic extract of M. bealei displayed a broad-spectrum antifungal activity against all four pathogenic fungi. Analysis of this crude extract by enrichment coupled with high-performance liquid chromatography revealed that berberine and palmatine are major metabolites. Additional inspections indicated berberine as the key compound responsible for the antifungal activity of the M. bealei ethanolic extract. Our study provides a better understanding of the potential of Vietnamese medicinal plant resources for combating fungal pathogens. This work also highlights that the citrus pathogen P. digitatum can be employed as a model fungus for screening the antifungal activity of botanicals.

Environmental STEM Study of the Oxidation Mechanism for Iron and Iron Carbide Nanoparticles.

The oxidation of solution-synthesized iron (Fe) and iron carbide (Fe2C) nanoparticles was studied in an environmental scanning transmission electron microscope (ESTEM) at elevated temperatures under oxygen gas. The nanoparticles studied had a native oxide shell present, that formed after synthesis, an ~3 nm iron oxide (FexOy) shell for the Fe nanoparticles and ~2 nm for the Fe2C nanoparticles, with small void areas seen in several places between the core and shell for the Fe and an ~0.8 nm space between the core and shell for the Fe2C. The iron nanoparticles oxidized asymmetrically, with voids on the borders between the Fe core and FexOy shell increasing in size until the void coalesced, and finally the Fe core disappeared. In comparison, the oxidation of the Fe2C progressed symmetrically, with the core shrinking in the center and the outer oxide shell growing until the iron carbide had fully disappeared. Small bridges of iron oxide formed during oxidation, indicating that the Fe transitioned to the oxide shell surface across the channels, while leaving the carbon behind in the hollow core. The carbon in the carbide is hypothesized to suppress the formation of larger crystallites of iron oxide during oxidation, and alter the diffusion rates of the Fe and O during the reaction, which explains the lower sensitivity to oxidation of the Fe2C nanoparticles.