Vidusskolēna gatavība pašrealizācijai un tās attīstība mācību procesā: vispārīgā pedagoģija

Advanced multifunctional protein particles encapsulated enzymes and antibodies were developed for enzymatic bioassays and immunoassays with colorimetric and fluorescent channels. A colorimetric channel based on color-substrate precipitation was assigned for enzymatic bioassays for the measurement of hydrogen peroxide with the lowest detectable concentration of 10 μM. A fluorescent channel based on fluorescent labeled antibodies was assigned for immunoassays for the measurement of mouse immunoglobulin G (M IgG) with the lowest detectable concentration of 1.25 μg L−1. The protein microparticles were fabricated with a template-assisted self-assembly technique termed “Protein Activation Spontaneous Self-assemble” (PASS). The multifunctional protein particles prepared with the PASS method have the advantages of high loading of analytical biomolecules, integrated biological functions, porous structure, and more importantly, they are optically transparent and fluorescence inactive. These unique features make our protein particles a new generation of bead-based platforms to perform enzyme bioassays and immunoassays

Modulating Electrode Kinetics for Discrimination of Dopamine by a PEDOT:COOH Interface Doped with Negatively Charged Tricarboxylate

The rapidly developing field of conducting polymers in organic electronics has many implications for bioelectronics. For biosensing applications, tailoring the functionalities of the conducting polymer’s surface is an efficient approach to improve both sensitivity and selectivity. Here, we demonstrated a facile and economic approach for the fabrication of a high-density, negatively charged carboxylic-acid-group-functionalized PEDOT (PEDOT:COOH) using an inexpensive ternary carboxylic acid, citrate, as a dopant. The polymerization efficiency was significantly improved by the addition of LiClO4 as a supporting electrolyte yielding a dense PEDOT:COOH sensing interface. The resulting PEDOT:COOH interface had a high surface density of carboxylic acid groups of 0.129 μmol/cm2 as quantified by the toluidine blue O (TBO) staining technique. The dopamine response measured with the PEDOT:COOH sensing interface was characterized by cyclic voltammetry with a significantly reduced ΔEp of 90 mV and a 3-fold increase in the Ipa value compared with those of the nonfunctionalized PEDOT sensing interface. Moreover, the cyclic voltammetry and electrochemical impedance spectroscopy results demonstrated the increased electrode kinetics and highly selective discrimination of dopamine (DA) in the presence of the interferents ascorbic acid (AA) and uric acid (UA), which resulted from the introduction of negatively charged carboxylic acid groups. The negatively charged carboxylic acid groups could favor the transfer, preconcentration, and permeation of positively charged DA to deliver improved sensing performance while repelling the negatively charged AA and UA interferents. The PEDOT:COOH interface facilitated measurement of dopamine over the range of 1–85 μM, with a sensitivity of 0.228 μA μM–1, which is 4.1 times higher than that of a nonfunctionalized PEDOT electrode (0.055 μA μM–1). Our results demonstrate the feasibility of a simple and economic fabrication of a high-density PEDOT:COOH interface for chemical sensing, which also has the potential for coupling with other biorecognition molecules via carboxylic acid moieties for the development of a range of advanced PEDOT-based biosensor

Tunable 3D nanofibrous and bio-functionalised PEDOT network explored as a conducting polymer-based biosensor

Conducting polymers that possess good electrochemical properties, nanostructured morphology and functionality for bioconjugation are essential to realise the concept of all-polymer-based biosensors that do not depend on traditional nanocatalysts such as carbon materials, metal, metal oxides or dyes. In this research, we demonstrated a facile approach for the simultaneous preparation of a bi-functional PEDOT interface with a tunable 3D nanofibrous network and carboxylic acid groups (i.e. Nano-PEDOT-COOH) via controlled co-polymerisation of EDOT and EDOT-COOH monomers, using tetrabutylammonium perchlorate as a soft-template. By tuning the ratio between EDOT and EDOT-COOH monomer, the nanofibrous structure and carboxylic acid functionalisation of Nano-PEDOT-COOH were varied over a fibre diameter range of 15.6 ± 3.7 to 70.0 ± 9.5 nm and a carboxylic acid group density from 0.03 to 0.18 μmol cm−2. The nanofibres assembled into a three-dimensional network with a high specific surface area, which contributed to low charge transfer resistance and high transduction activity towards the co-enzyme NADH, delivering a wide linear range of 20–960 μM and a high sensitivity of 0.224 μA μM−1 cm−2 at the Nano-PEDOT-COOH50% interface. Furthermore, the carboxylic acid groups provide an anchoring site for the stable immobilisation of an NADH-dependent dehydrogenase (i.e. lactate dehydrogenase), via EDC/S–NHS chemistry, for the fabrication of a Bio-Nano-PEDOT-based biosensor for lactate detection which had a response time of less than 10 s over the range of 0.05–1.8 mM. Our developed bio-Nano-PEDOT interface shows future potential for coupling with multi-biorecognition molecules via carboxylic acid groups for the development of a range of advanced all-polymer biosensor

Conducting polymer-reinforced laser-irradiated graphene as a heterostructured 3D transducer for flexible skin patch biosensors

Flexible skin patch biosensors are promising for the noninvasive determination of physiological parameters in perspiration for fitness and health monitoring. However, various prerequisites need to be met for the development of such biosensors, including the creation of a flexible conductive platform, bending/contact stability, fast electrochemical kinetics, and immobilization of biomolecules. Here, we describe a conducting polymer-reinforced laser-irradiated graphene (LIG) network as a heterostructured three-dimensional (3D) transducer for flexible skin patch biosensors. LIG with a hierarchically interconnected graphene structure is geometrically patterned on polyimide via localized laser irradiation as a flexible conductive platform, which is then reinforced by poly(3,4-ethylenedioxythiophene) (PEDOT) as a conductive binder (PEDOT/LIG) with improved structural/contact stability and electrochemical kinetics. The interconnected pores of the reinforced PEDOT/LIG function as a 3D host matrix for high loading of “artificial” (Prussian blue, PB) and natural enzymes (lactate oxidase, LOx), forming a compact and heterostructured 3D transducer (LOx/PB-PEDOT/LIG) for lactate biosensing with excellent sensitivity (11.83 μA mM–1). We demonstrated the fabrication of flexible skin patch biosensors comprising a custom-built integrated three-electrode system achieve amperometric detection of lactate in artificial sweat over a wide physiological linear range of 0–18 mM. The advantage of this facile and versatile transducer is further illustrated by the development of a folded 3D wristband lactate biosensor and a dual channel biosensors for simultaneous monitoring of lactate and glucose. This innovative design concept of a heterostructured transducer for flexible biosensors combined with a versatile fabrication approach could potentially drive the development of new wearable and skin-mountable biosensors for monitoring various physiological parameters in biofluids for noninvasive fitness and health management

Soft and flexible material-based affinity sensors

Recent advances in biosensors and point-of-care (PoC) devices are poised to change and expand the delivery of diagnostics from conventional lateral-flow assays and test strips that dominate the market currently, to newly emerging wearable and implantable devices that can provide continuous monitoring. Soft and flexible materials are playing a key role in propelling these trends towards real-time and remote health monitoring. Affinity biosensors have the capability to provide for diagnosis and monitoring of cancerous, cardiovascular, infectious and genetic diseases by the detection of biomarkers using affinity interactions. This review tracks the evolution of affinity sensors from conventional lateral-flow test strips to wearable/implantable devices enabled by soft and flexible materials. Initially, we highlight conventional affinity sensors exploiting membrane and paper materials which have been so successfully applied in point-of-care tests, such as lateral-flow immunoassay strips and emerging microfluidic paper-based devices. We then turn our attention to the multifarious polymer designs that provide both the base materials for sensor designs, such as PDMS, and more advanced functionalised materials that are capable of both recognition and transduction, such as conducting and molecularly imprinted polymers. The subsequent content discusses wearable soft and flexible material-based affinity sensors, classified as flexible and skin-mountable, textile materials-based and contact lens-based affinity sensors. In the final sections, we explore the possibilities for implantable/injectable soft and flexible material-based affinity sensors, including hydrogels, microencapsulated sensors and optical fibers. This area is truly a work in progress and we trust that this review will help pull together the many technological streams that are contributing to the field

Precise and rapid solvent-assisted geometric protein self-patterning with submicron spatial resolution for scalable fabrication of microelectronic biosensors

We report a novel manufacturing method for microelectronic biosensors with a one-step wet/de-wet micropatterning of proteins onto printed metal microelectrode array supported by a hydrophobic perfluoropolymer substrate. The method exploits the phenomenon that protein adsorption toward a hydrophobic perfluoropolymer surface is drastically suppressed by self-assembly of proteins into micelles in a solvent-buffer mixture, followed by a rapid wet/de-wet process to localize the protein molecules onto the hydrophilic microelectrodes. The method affords protein micropatterning with 5 mm spatial resolution while preserving biological function and is applicable to various proteins such as albumin, enzymes, antibodies and avidin . By combining the protein micropatterning with metal nanoparticle chemisorption printing of the microelectrode array, we demonstrate as a model, facile fabrication of a microelectronic glucose biosensor supporting convergent analyte diffusion and thus showing typical steady-state I-V characteristics and fast steady-state current response (~20-60 s) together with an ultra-wide linear dynamic range (2-100 mM). Our findings provide a new technical solution for precise and accurate coupling of biomolecules with a microelectronic array interface with important implications for the scale up and manufacture of diagnostics, biofuel cells and bioelectronic devices

Processable and nanofibrous polyaniline:polystyrene-sulphonate (nano-PANI:PSS) for the fabrication of catalyst-free ammonium sensors and enzyme-coupled urea biosensors

Tailoring conducting polymers (CPs) such as polyaniline (PANI) to deliver the appropriate morphology, electrochemical properties and processability is essential for the development of effective polymer-based electrochemical sensors and biosensors. Composite PANI electrodes for the detection of ammonium (NH4+) have been previously reported, but have been limited by their reliance on the electrocatalytic reaction between NH4+ and a metal/nano-catalyst. We report an advanced processable and nanofibrous polyaniline:polystyrene-sulphonate (nano-PANI:PSS) as a functional ink for the fabrication of catalyst-free NH4+ sensors and enzyme-coupled urea biosensors. The PSS provides both a soft-template for nanofibre formation and a poly-anionic charge compensator, enabling the detection of NH4+ based on an intrinsic doping/de-doping mechanism. The nanostructured morphology, chemical characteristics and electrochemical properties of the nano-PANI:PSS were characterised. We fabricated 3D-hierarchical sensor interfaces composed of inter-connected nano-PANI:PSS fibres (diameter of ~50.3 ± 4.8 nm) for the detection of NH4+ with a wide linear range of 0.1–11.5 mM (R2 = 0.996) and high sensitivity of 106 mA M−1 cm−2. We further demonstrated the coupling of the enzyme urease with the nano-PANI:PSS to create a urea biosensor with an innovative biocatalytic product-to-dopant relay mechanism for the detection of urea, with a linear range of 0.2–0.9 mM (R2 = 0.971) and high sensitivity of 41 mA M−1 cm−2. Moreover, the nano-PANI:PSS-based sensors show good selectivity for the detection of NH4+and urea in a urine model containing common interfering molecules. This processable and fibrous nano-PANI:PSS provides new advance on CP-based transducer materials in the emerging field of printed organic sensors and biosensors

Bi-functional sulphonate-coupled reduced graphene oxide as an efficient dopant for a conducting polymer with enhanced electrochemical performance

The rapidly emerging field of organic bioelectronics has witnessed the wide use of conducting polymers (CPs) to fabricate advanced chemically modified electrodes (CMEs) for biosensors and biomedical devices. The electrochemical performance of the CPs in such devices is closely related to the quality and physiochemical nature of the dopants. A bi-functional graphene oxide derivative with high reduction degree and negatively-charged sulphonate functionality, i.e. sulphonate-coupled reduced graphene oxide (S-RGO), was developed and used as an efficient dopant for a CP with enhanced electrochemical performance. The S-RGO was synthesised via a facile one-pot hydrothermal reaction using 4-hydrazinobenzosulphonic acid (4-HBS) as reductant and sulphonate precursor simultaneously. The resulting S-RGO possesses high aqueous dispersion stability (more than 6 months), high electrical conductivity (1493.0 S m−1) and sulphonate functionality. Due to these specific properties, S-RGO demonstrated improved electropolymerisation efficiency for poly(3,4-ethylenedioxythiophene) (PEDOT) proving an effective dopant for the preparation of a PEDOT:S-RGO film (5 mC) with faster polymerisation time (37 s) compared to the conventional 2D dopants GO (PEDOT:GO, 129 s) and RGO (PEDOT:RGO, 66 s). The resulting PEDOT:S-RGO appeared as a homogenous film with uniformly distributed S-RGO dopant, low equivalent series resistance and low charge transfer resistance. Moreover, the electrochemical transduction performance of the PEDOT:S-RGO interface was evaluated with 4 different analytes, including ferric/ferrocyanide redox probe, dopamine, nicotinamide adenine dinucleotide and hydrogen peroxide. As a result of the synergistic effect of S-RGO and PEDOT, the PEDOT:S-RGO demonstrated enhanced electrochemical performance with respect to faster electrode kinetics (smaller ΔEp), ∼2 and ∼4 times increased current responses, and lower peak potentials compared to PEDOT:GO and PEDOT:RGO. This bi-functional S-RGO dopant combined the advantages of conventional GO and RGO to deliver sulphonate functionality and high conductivity for the preparation of advanced PEDOT interface with improved electrochemical performance, that could potentially be applied for applications in electrochemical sensors, biosensors and bioelectronic device

IL-33 ameliorates Alzheimer’s disease-like pathology and cognitive decline

Alzheimer’s disease (AD) is a devastating condition with no known effective treatment. AD is characterized by memory loss as well as impaired locomotor ability, reasoning, and judgment. Emerging evidence suggests that the innate immune response plays a major role in the pathogenesis of AD. In AD, the accumulation of β-amyloid (Aβ) in the brain perturbs physiological functions of the brain, including synaptic and neuronal dysfunction, microglial activation, and neuronal loss. Serum levels of soluble ST2 (sST2), a decoy receptor for interleukin (IL)-33, increase in patients with mild cognitive impairment, suggesting that impaired IL-33/ST2 signaling may contribute to the pathogenesis of AD. Therefore, we investigated the potential therapeutic role of IL-33 in AD, using transgenic mouse models. Here we report that IL-33 administration reverses synaptic plasticity impairment and memory deficits in APP/PS1 mice. IL-33 administration reduces soluble Aβ levels and amyloid plaque deposition by promoting the recruitment and Aβ phagocytic activity of microglia; this is mediated by ST2/p38 signaling activation. Furthermore, IL-33 injection modulates the innate immune response by polarizing microglia/macrophages toward an antiinflammatory phenotype and reducing the expression of proinflammatory genes, including IL-1β, IL-6, and NLRP3, in the cortices of APP/PS1 mice. Collectively, our results demonstrate a potential therapeutic role for IL-33 in AD

Integrated printed microfluidic biosensors

Integrated printed microfluidic biosensors are one of the most recent point-of-care (POC) sensor developments. Fast turnaround time for production and ease of customization, enabled by the integration of recognition elements and transducers, are key for on-site biosensing for both healthcare and industry and for speeding up translation to real-life applications. Here, we provide an overview of recent progress in printed microfluidics, from the 2D to the 4D level, accompanied by novel sensing element integration. We also explore the latest trends in integrated printed microfluidics for healthcare, especially POC diagnostics, and food safety applications