An ImmunoFET Coupled with an Immunomagnetic Preconcentration Technique for the Sensitive EIS Detection of HF Biomarkers.

We propose a new strategy using a sandwich approach for the detection of two HF biomarkers: tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10). For this purpose, magnetic nanoparticles (MNPs) (MNPs@aminodextran) were biofunctionalized with monoclonal antibodies (mAbs) using bis (sulfosuccinimidyl) suberate (BS3) as a cross-linker for the pre-concentration of two biomarkers (TNF-α and IL-10). In addition, our ISFETs were biofunctionalized with polyclonal antibodies (pAbs) (TNF-α and IL-10). The biorecognition between pAbs immobilized on the ISFET and the pre-concentrate antigen (Ag) on MNPs was monitored using electrochemical impedance spectroscopy (EIS). Our developed ImmunoFET showed a low detection limit (0.03 pg/mL) toward our target analyte when compared to previously published electrochemical immunosensors. It showed a higher sensitivity than for other HF biomarkers. Finally, the standard addition method was used to determine the unknown concentration in artificial saliva. The results matched with the expected values well.

Fast impedimetric immunosensing of IgGs associated with peanut and hazelnut allergens.

Food allergies trigger a variety of clinical adverse symptoms and clinical evidence suggests that the presence of food allergy-related IgG can be helpful in the diagnosis when analyzed at the peptide-epitope level. To validate and select the peptides based on their specificity toward hazelnut or peanut epitopes, the authors of this study developed a silicon-based microchip coupled with click-chemistry bound peptides identified by the Fraunhofer Institute for Cell Therapy and Immunology. Peptides related to hazelnut and peanut allergies were identified and used to develop a silicon-based microchip. Peptides were coupled with click-chemistry to the sensor surface. The immunosensor was developed by electrografting diazotized amino phenylacetic acid and subsequently, dibenzocyclooctyne-amine (DBCO-NH2) was used as click-chemistry to allow coupling of the peptides with a C-terminal linker and azide structure. Energy-dispersive X-ray spectroscopy, electrochemical impedance spectroscopy (EIS), and fluorescence microscopy techniques have been used to analyze the bio-functionalization of the developed electrode. The peptide-epitope recognition was studied for seven allergen-derived peptides. The electrochemical responses were studied with sera from rabbits immunized with hazelnut and peanut powder. The microchips functionalized with the chosen peptides (peanut peptides T12 and EO13 and hazelnut peptides S4 and EO14 with an RSD of 4%, 3%, 9%, and 1% respectively) demonstrated their ability to specifically detect prevalent anti-nut related IgGs in rabbit sera in a range of dilutions from 1:500000 (0.0002%) until 1:50000 (0.002%). In addition, the other peptides showed promising differentiation abilities which can be further studied to perform multivariable detection fingerprint of anti-allergens in blood sera.

Exploring the Versatility of Microemulsions in Cutaneous Drug Delivery: Opportunities and Challenges.

Microemulsions are novel drug delivery systems that have garnered significant attention in the pharmaceutical research field. These systems possess several desirable characteristics, such as transparency and thermodynamic stability, which make them suitable for delivering both hydrophilic and hydrophobic drugs. In this comprehensive review, we aim to explore different aspects related to the formulation, characterization, and applications of microemulsions, with a particular emphasis on their potential for cutaneous drug delivery. Microemulsions have shown great promise in overcoming bioavailability concerns and enabling sustained drug delivery. Thus, it is crucial to have a thorough understanding of their formulation and characterization in order to optimize their effectiveness and safety. This review will delve into the different types of microemulsions, their composition, and the factors that affect their stability. Furthermore, the potential of microemulsions as drug delivery systems for skin applications will be discussed. Overall, this review will provide valuable insights into the advantages of microemulsions as drug delivery systems and their potential for improving cutaneous drug delivery.

Immuno field-effect transistor (ImmunoFET) for detection of salivary cortisol using potentiometric and impedance spectroscopy for monitoring heart failure.

Cortisol, a steroid hormone mostly known as "the stress hormone," plays many essential functions in humans due its involvement in several metabolic pathways. It is well-known that cortisol dysregulation is implied in evolution and progression of several chronic pathologies, including cardiac diseases such as heart failure (HF). However, although several sensors have been proposed to date for the determination of cortisol, none of them has been designed for its determination in saliva in order to monitor HF progression. In this work, a silicon nitride based Immuno field-effect transistor (ImmunoFET) has been proposed to quantify salivary cortisol for HF monitoring. Sensitive biological element was represented by anti-cortisol antibody bound onto the ISFET gate via 11-triethoxysilyl undecanal (TESUD) by vapor-phase method. Potentiometric and electrochemical impedance spectroscopy (EIS) measurements were carried out for preliminary investigations on device responsiveness. Subsequently, a more sensitive detection was obtained using electrochemical EIS. The proposed device has proven to have a linear response (R2 always >0.99), to be sensitive (with a limit of detection, LoD, of 0.005 ± 0.002 ng/mL), selective in case of other HF biomarkers (e.g. N-terminal pro B-type natriuretic peptide (NT-proBNP), tumor necrosis factor-alpha (TNF-α), and interleukin 10 (IL-10)), and accurate in cortisol quantification in saliva sample by performing the standard addition method.

Core-shell micro/nanocapsules: from encapsulation to applications.

Encapsulation is the way to wrap or coat one substance as a core inside another tiny substance known as a shell at micro and nano scale for protecting the active ingredients from the exterior environment. A lot of active substances, such as flavours, enzymes, drugs, pesticides, vitamins, in addition to catalysts being effectively encapsulated within capsules consisting of different natural as well as synthetic polymers comprising poly(methacrylate), poly(ethylene glycol), cellulose, poly(lactide), poly(styrene), gelatine, poly(lactide-co-glycolide)s, and acacia. The developed capsules release the enclosed substance conveniently and in time through numerous mechanisms, reliant on the ultimate use of final products. Such technology is important for several fields counting food, pharmaceutical, cosmetics, agriculture, and textile industries. The present review focuses on the most important and high-efficiency methods for manufacturing micro/nanocapsules and their several applications in our life.

Magnetic nanoparticles: multifunctional tool for cancer therapy.

INTRODUCTION: Cancer has one of the highest mortality rates globally. The traditional therapies used to treat cancer have harmful adverse effects. Considering these facts, researchers have explored new therapeutic possibilities with enhanced benefits. Nanoparticle development for cancer detection, in addition to therapy, has shown substantial progress over the past few years. AREA COVERED: Herein, the latest research regarding cancer treatment employing magnetic nanoparticles (MNPs) in chemo-, immuno-, gene-, and radiotherapy along with hyperthermia is summarized, in addition to their physio-chemical features, advantages, and limitations for clinical translation have also been discussed. EXPERT OPINION: MNPs are being extensively investigated and developed into effective modules for cancer therapy. They are highly functional tools aimed at cancer therapy owing to their excellent superparamagnetic, chemical, biocompatible, physical, and biodegradable properties.

Nanocarriers based novel and effective drug delivery system.

Nanotechnology has ultimately come into the domain of drug delivery. Nanosystems for delivery of drugs are promptly emerging science utilizing different nanoparticles as carriers. Biocompatible and stable nanocarriers are novel diagnosis tools or therapy agents for explicitly targeting locates with controllable way. Nanocarriers propose numerous advantages to treat diseases via site-specific as well as targeted delivery of particular therapeutics. In recent times, there are number of outstanding nanocarriers use to deliver bio-, chemo-, or immuno- therapeutic agents to obtain effectual therapeutic reactions and to minimalize unwanted adverse-effects. Nanoparticles possess remarkable potential for active drug delivery. Moreover, conjugation of drugs with nanocarriers protects drugs from metabolic or chemical modifications, through their way to targeted cells and hence increased their bioavailability. In this review, various systems integrated with different types of nanocarriers (inorganic. organic, quantum dots, and carbon nanotubes) having different compositions, physical and chemical properties have been discussed for drug delivery applications.

One-step impedimetric NT-proBNP aptasensor targeting cardiac insufficiency in artificial saliva.

Currently, sensitive and accurate approaches for diagnosis, rapid assessment, and cardiac biomarker monitoring in patients with heart failure are needed. In this context, the advantages of aptamers over traditional antibodies have been employed to fabricate a single-step impedimetric N-terminal pro b-type natriuretic peptide (NT-proBNP)-modified gold microelectrode array. The development of an electrochemical aptasensing platform was based on the coimmobilization of alkanethiol self-assembled monolayers and amine-terminated aptamer that specifically recognized cardiac NT-proBNP protein resulting in charge electron transfer. Electroimpedimetric signals of the sensor were observed to be linear to the NT-proBNP concentrations in the range of 5.0 × 10-3 to 1.0 pg mL-1 (R2 = 0.9624), while achieving a low detection limit of 5.0 × 10-3 pg mL-1. Clinically relevant detection levels for NT-proBNP were achieved in a simple, rapid, and label-free measurement using artificial saliva, which was highlighted to be specific, regenerative, and selective over potential interferers occurring during the processes of cardiac insufficiency, Therefore, the novel NT-proBNP aptasensor is a promising point-of-care tool exhibiting safe, non-invasive, affordable, and non-prescription home use accessible to overcome the limitations associated with conventional ELISA and previous aptasensing.

Non-covalent π-π functionalized Gii-senseⓇ graphene foam for interleukin 10 impedimetric detection.

Monitoring Interleukin 10 (IL-10) is essential for understanding the vast responses of T-cells in cancer, autoimmunity, and internal homeostasis after physical stress. However, current diagnostic methods are complex and more focused on medical screening rather than point-of-care monitoring. Biosensors based on graphene's conductivity and flexibility are attractive to offer simple single-use and reduced handling. However, oxidation of its carbon lattice to develop functional moieties for biomolecule immobilization cuts down its electronic conductivity potential. In this work, the authors present a microfluidic lab-on-chip device for simple impedimetric monitoring of IL-10 based on graphene foam (GF) flexible electrodes. Graphene's structure was maintained by employing π-π non-covalent functionalization with pyrene carboxylic acid (PCA). Impedimetric measurements could be performed in low ionic strength phosphate-buffered saline (LI-PBS). The PCA-antibody modification showed to endure the incubation, measurement, and washing processes performed in the microfluidic device. Electrode modification and measurements were characterized by, electrochemical impedance spectroscopy (EIS), contact angle, and scanning electron microscopy. From the contact angle results, we found that the wettability of the graphene surface increased gradually after each modification step. Detection measurements performed in the 3D-printed microfluidic device showed a linear response between 10 fg/mL to 100 fg/mL with a limit of detection (LOD) of 7.89 fg/mL in artificial saliva. With these features, the device was used to quantify IL-10 samples by the standard addition method for 10 fg and 50 fg with recoveries between 82% and 99%. Specificity was evaluated towards interleukin 6, TNF-⍺ and bovine serum albumin.

A novel electrochemical strategy for NT-proBNP detection using IMFET for monitoring heart failure by saliva analysis.

Heart failure (HF) is a chronic cardiovascular disease that represents main cause of mortality worldwide, particularly for elderly. N-terminal pro-brain natriuretic peptide (NT-proBNP) was identified as the gold standard biomarker for HF diagnosis and therapy monitoring. Presently, saliva analysis represents an emerging and powerful tool for clinical applications and electrochemical immunosensors have shown their potential in Healthcare applications as selective and reliable systems for detecting clinical biomarkers. This work presents the detection of NT-proBNP in saliva samples by an immunologically modified Field effect Transistor (IMFET). TESUD ((11-triethoxysilyl) undecanal) was used as cross-linker to immobilise anti-NT-proBNP antibody onto the device. Our IMFET that was then tested in different matrices (e.g. phosphate buffered saline (PBS), artificial saliva and human saliva) using electrochemical impedance spectroscopy (EIS), and it resulted selective to NT-proBNP with good sensitivity (detection limit of 0.02 pg/mL) and a wide linear range (0.02-1 pg/mL and 0.5-20 pg/mL). Finally, NT-proBNP concentration in ten saliva samples was determined by performing the standard addition method. An enzyme-linked immunosorbent assay was used for confirming IMFET results, highlighting both IMFET accuracy (analyte recovery of 99 ± 8%) and precision (coefficient of variation always <10%), and supporting the suitability of the device for determining salivary NT-proBNP.

A Novel Cortisol Immunosensor Based on a Hafnium Oxide/Silicon Structure for Heart Failure Diagnosis.

Assessing cortisol levels in human bodies has become essential to diagnose heart failure (HF). In this work, we propose a salivary cortisol detection strategy as part of an easily integrable lab-on-a-chip for detection of HF biomarkers. Our developed capacitive immunosensor based on hafnium oxide (HfO2)/silicon structure showed good linearity between increasing cortisol concentration and the charge-transfer resistance/capacitance. Moreover, the developed biosensor was demonstrated to be highly selective toward cortisol compared to other HF biomarkers such as tumor necrosis factor (TNF-α) and N-terminal pro-brain natriuretic peptide (NT-proBNP). The precision of our developed biosensor was evaluated, and the difference between the determined cortisol concentration in saliva and its expected one is <18%.

Biodegradable porous micro/nanoparticles with thermoresponsive gatekeepers for effective loading and precise delivery of active compounds at the body temperature.

Stimuli-responsive controlled delivery systems are of interest for preventing premature leakages and ensuring precise releases of active compounds at target sites. In this study, porous biodegradable micro/nanoparticles embedded with thermoresponsive gatekeepers are designed and developed based on Eudragit RS100 (PNIPAM@RS100) and poly(N-isopropylacrylamide) via a double emulsion solvent evaporation technique. The effect of initiator types on the polymerization of NIPAM monomer/methylene-bis-acrylamide (MBA) crosslinker was investigated at 60 °C for thermal initiators and ambient temperature for redox initiators. The crosslinked PNIPAM plays a key role as thermal-triggered gatekeepers with high loading efficiency and precise release of a model active compound, Nile Blue A (NB). Below the volume phase transition temperature (TVPT), the gatekeepers possess a swollen conformation to block the pores and store NB within the cavities. Above its TVPT, the chains rearrange, allowing gate opening and a rapid and constant release rate of the compound until completion. A precise "on-off" switchable release efficiency of PNIPAM@RS100 was demonstrated by changing the temperatures to 4 and 40 °C. The materials are a promising candidate for controlled drug delivery systems with a precise and easy triggering mechanism at the body temperature for effective treatments.

Spatially hierarchical nano-architecture for real time detection of Interleukin-8 cancer biomarker.

In the present work we have developed two hierarchical nano-architectures based electrochemical immunosensors for the detection of interleukin-8 (IL-8) cytokine tumor biomarker. A comparative study has been performed for spatial nano-architectures and their relative sensing to establish the model for real time monitoring. With the first platform, the recognition layer consisted with immobilised IL-8 on aminothiol modified gold electrodes. In the second approach, the activated multi walled carbon nanotubes (MWCNT-COOH) were added in the functionalisation process by covalent attachment between the functionalities NH2 of aminothiol and the functionalities COOH of carbon nanotubes. The surface topology of the recognition layer has been characterised by atomic force spectroscopy (AFM) and contact angle (CA) measurements. The electrochemical response of the developed sensor was measured by electrochemical impedance spectroscopy (EIS). A side-by-side comparison showed that aminothiol/activated MWCNTs/anti-IL-8 based impedimetric immunosensor exhibits high reproducibility (The relative standard deviation (R.S.D) = 3.2%, n = 3) with high stability. The present sensor allows evaluating a lower detection limit of 0.1 pg mL-1 with a large dynamic sensitivity range from 1 pg mL-1to 1000 pg mL-1 covering the entire clinical therapeutic window. The developed MWCNTs based immunosensor has been calibrated by determining IL-8 in artificial plasma and showed a selective response to IL-8 even in the interfering environment of other cytokines such as Interleukin-1 (IL-1) and Interleukin-6 (IL-6).

Advancement in Nanoparticle-based Biosensors for Point-of-care In vitro Diagnostics.

Recently, there has been great progress in the field of extremely sensitive and precise detection of bioanalytes. The importance of the utilization of nanoparticles in biosensors has been recognized due to their unique properties. Specifically, nanoparticles of gold, silver, and magnetic plus graphene, quantum dots, and nanotubes of carbon are being keenly considered for utilization within biosensors to detect nucleic acids, glucose, or pathogens (bacteria as well as a virus). Taking advantage of nanoparticles, faster and sensitive biosensors can be developed. Here, we review the nanoparticles' contribution to the biosensors field and their potential applications.

Contribution of magnetic particles in molecular diagnosis of human viruses.

Viral diseases are the primary source of death, making a worldwide influence on healthcare, social, and economic development. Thus, diagnosis is the vital approach to the main aim of virus control and elimination. On the other hand, the prompt advancement of nanotechnology in the field of medicine possesses the probability of being beneficial to diagnose infections normally in labs as well as specifically. Nanoparticles are efficiently in use to make novel strategies because of permitting analysis at cellular in addition to the molecular scale. Henceforth, they assist towards pronounced progress concerning molecular analysis at the nanoscale. In recent times, magnetic nanoparticles conjugated through covalent bonds to bioanalytes for instance peptides, antibodies, nucleic acids, plus proteins are established like nanoprobes aimed at molecular recognition. These modified magnetic nanoparticles could offer a simple fast approach for extraction, purification, enrichment/concentration, besides viruses' recognition precisely also specifically. In consideration of the above, herein insight and outlook into the limitations of conventional methods and numerous roles played by magnetic nanoparticles to extract, purify, concentrate, and additionally in developing a diagnostic regime for viral outbreaks to combat viruses especially the ongoing novel coronavirus (COVID-19).

Mathematical Modelling of Glyphosate Molecularly Imprinted Polymer-Based Microsensor with Multiple Phenomena.

The massive and careless use of glyphosate (GLY) in agricultural production raises many questions regarding environmental pollution and health risks, it is then important to develop simple methods to detect it. Electrochemical impedance spectroscopy (EIS) is an effective analytical tool for characterizing properties at the electrode/electrolyte interface. It is useful as an analytical procedure, but it can also help in the interpretation of the involved fundamental electrochemical and electronic processes. In this study, the impedance data obtained experimentally for a microsensor based on molecularly imprinted chitosan graft on 4-aminophenylacetic acid for the detection of glyphosate was analyzed using an exact mathematical model based on physical theories. The procedure for modeling experimental responses is well explained. The analysis of the observed impedance response leads to estimations of the microscopic parameters linked to the faradic and capacitive current. The interaction of glyphosate molecules with the imprinted sites of the CS-MIPs film is observed in the high frequency range. The relative variation of the charge transfer resistance is proportional to the log of the concentration of glyphosate. The capacitance decreases as the concentration of glyphosate increases, which is explained by the discharging of the charged imprinted sites when the glyphosate molecule interacts with the imprinted sites through electrostatic interactions. The phenomenon of adsorption of the ions in the CMA film is observed in the low frequency range, this phenomenon being balanced by the electrostatic interaction of glyphosate with the imprinted sites in the CS-MIPs film.

Microfluidic-based nanoparticle synthesis and their potential applications.

A lot of substantial innovation in advancement of microfluidic field in recent years to produce nanoparticle reveals a number of distinctive characteristics, for instance, compactness, controllability, fineness in process, and stability along with minimal reaction amount. Recently, a prompt development, as well as realization in the production of nanoparticles in microfluidic environment having dimension of micro to nanometers and constituents extending from metals, semiconductors to polymers, has been made. Microfluidics technology integrates fluid mechanics for the production of nanoparticles having exclusive with homogenous sizes, shapes, and morphology, which are utilized in several bioapplications such as biosciences, drug delivery, and healthcare including food engineering. Nanoparticles are usually well-known for having fine and rough morphology because of their small dimensions including exceptional physical, biological, chemical, and optical properties. Though the orthodox procedures need huge instruments, costly autoclaves, use extra power, extraordinary heat loss, as well as take surplus time for synthesis. Additionally, this is fascinating to systematize, assimilate, in addition, to reduce traditional tools onto one platform to produce micro and nanoparticles. The synthesis of nanoparticles by microfluidics permits fast handling besides better efficacy of method utilizing the smallest components for process. Herein, we will focus on synthesis of nanoparticles by means of microfluidic devices intended for different bioapplications.

Selective Antibody-Free Sensing Membranes for Picogram Tetracycline Detection.

As an antibody-free sensing membrane for the detection of the antibiotic tetracycline (TC), a liquid PVC membrane doped with the ion-pair tetracycline/θ-shaped anion [3,3'-Co(1,2-C2B9H11)2]- ([o-COSAN]-) was formulated and deposited on a SWCNT modified gold microelectrode. The chosen transduction technique was electrochemical impedance spectroscopy (EIS). The PVC membrane was composed of: the tetracycline/[o-COSAN]- ion-pair, a plasticizer. A detection limit of 0.3 pg/L was obtained with this membrane, using bis(2-ethylhexyl) sebacate as a plasticizer. The sensitivity of detection of tetracycline was five times higher than that of oxytetracycline and of terramycin, and 22 times higher than that of demeclocycline. A shelf-life of the prepared sensor was more than six months and was used for detection in spiked honey samples. These results open the way to having continuous monitoring sensors with a high detection capacity, are easy to clean, avoid the use of antibodies, and produce a direct measurement.

Innovative electrochemical sensor for the precise determination of the new antiviral COVID-19 treatment Favipiravir in the presence of coadministered drugs.

Due the current pandemic of COVID-19, an urgent need is required for serious medical treatments of a huge number of patients. The world health organization (WHO) approved Favipiravir (FAV) as a medication for patients infected with corona virus. In the current study, we report the first simple electrochemical, greatly sensitive sensor using MnO2-rGO nanocomposite for the accurate determination of Favipiravir (FAV). The developed sensor showed a high improvement in the electrochemical oxidation of FAV comparing to the unmodified screen-printed electrode (SPE). The suggested platform constituents and the electrochemical measurements parameters were studied. Under optimal experimental parameters, a current response to the concentration change of FAV was found to be in the linear range of 1.0 × 10-8-5.5 × 10-5 M at pH 7.0 with a limit of detection 0.11 µM and a quantification limit of 0.33 µM. The developed platform was confirmed by the precise analysis of FAV in real samples including dosage form and plasma. The developed platform can be applied in different fields of industry quality control and clinical analysis laboratories for the FAV determination.

Electrochemical Impedance Spectroscopy Microsensor Based on Molecularly Imprinted Chitosan Film Grafted on a 4-Aminophenylacetic Acid (CMA) Modified Gold Electrode, for the Sensitive Detection of Glyphosate.

A novel electrochemical impedance spectroscopy (EIS) microsensor was implemented for the dosage of traces of glyphosate, in real and synthetic water samples. Molecularly imprinted chitosan was covalently immobilized on the surface of the microelectrode previously modified with 4-aminophenylacetic acid (CMA). The characterization of the resulting microelectrodes was carried out by using cyclic voltammetry measurement (CV), scanning electron microscopy (SEM), and electrochemical impedance spectrometry (EIS). EIS responses of the CS-MIPs/CMA/Au microsensor toward GLY was well-proportional to the concentration in the range from 0.31 × 10-9 to 50 × 10-6 mg/mL indicating a good correlation. The detection limit of GLY was 1 fg/mL (S/N = 3). Moreover, this microsensor showed good reproducibility and repeatability, high selectivity, and can be used for the detection of GLY in river water.