Paper-Based Analytical Devices for Cancer Liquid Biopsy.

Liquid biopsies have caused a significant revolution in cancer diagnosis, and the use of point of care (PoC) platforms has the potential to bring liquid biopsy-based cancer detection closer to patients. These platforms provide rapid and on-site analysis by reducing the time between sample collection and results output. The aim of this tutorial content is to provide readers an in-depth understanding regarding the choice of the ideal sensing platform suitable for specific cancer-related biomarkers.

Facile and Affordable Design of MXene-Co3 O4 -Based Nanocomposites for Detection of Hydrogen Peroxide in Cancer Cells: Toward Portable Tool for Cancer Management.

Hydrogen peroxide (H2 O2 ) is a primary reactive oxygen species (ROS) that can act as a chemical signal in developing and progressing serious and life-threatening diseases like cancer. Due to the stressful nature of H2 O2 , there is an urgent need to develop sensitive analytical approaches to be applied to various biological matrices. Herein, a portable point-of-care electrochemical system based on MXene-Co3 O4 nanocomposites to detect H2 O2 in different cancer cell-lines is presented. The developed sensor is affordable, disposable, and highly selective for H2 O2 detection. This approach achieves a dynamic linear range of 75 µm with a LOD of 0.5 µm and a LOQ of 1.6 µm. To improve the practical application, the level of ROS is evaluated both in cancer cell lines MDA-MB-231 and DU145, respectively, to breast and prostate cancers, and in healthy HaCat cells. Moreover, the same cancer cells are treated with transforming growth factor-ß1, and MXene-Co3 O4 modified strip is capable to monitorROS variation. The results are satisfactory compared with the cellular ROS fluorescent assay based on DCFH/DCFH-DA. These results open new perspectives for real-time monitoring of cancer progression and the efficacy of the therapy.

Design of a printed electrochemical strip towards miRNA-21 detection in urine samples: optimization of the experimental procedures for real sample application.

MicroRNAs (miRNAs) are clinical biomarkers for various human diseases, including cancer. They have been found in liquid biopsy samples, including various bodily fluids. They often play an important role in the early diagnosis and prognosis of cancer, and the development of simple and effective analytical methods would be of pivotal importance for the entire community. The determination of these targets may be affected by the different physicochemical parameters of the specimen of interest. In this work, an electrochemical detection platform for miRNA based on a screen-printed gold electrode was developed. In the present study, miRNA-21 was selected as a model sequence, due to its role in prostate, breast, colon, pancreatic, and liver cancers. A DNA sequence modified with methylene blue (MB) was covalently bound to the electrochemical strip and used to detect the selected target miRNA-21. After optimization of selected parameters in standard solutions, including the study of the effect of pH, the presence of interferent species, and NaCl salt concentration in the background, the application of square-wave voltammetry (SWV) technique allowed the detection of miRNA-21 down to a limit in the order of 2 nM. The developed device was then applied to several urine samples. In this case too, the device showed high selectivity in the presence of the complex matrix, satisfactory repeatability, and a limit of detection in the order of magnitude of nM, similarly as what observed in standard solutions.

Epidemiology, virology and clinical aspects of hantavirus infections: an overview.

At the end of 2019 and 2020s, a wave of coronavirus disease 19 (COVID-19) epidemics worldwide has catalyzed a new era of 'communicable infectious diseases'. However, the world is not currently prepared to deal with the growing burden of COVID-19, with the unexpected arrival of Hantavirus infection heading to the next several healthcare emergencies in public. Hantavirus is a significant class of zoonotic pathogens of negative-sense single-stranded ribonucleic acid (RNA). Hemorrhagic renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) are the two major clinical manifestations. Till date, there is no effective treatments or vaccines available, public awareness and precautionary measures can help to reduce the spread of hantavirus disease. In this study, we outline the epidemiology, virology, clinical aspects, and existing HFRS and HCPS management approaches. This review will give an understanding of virus-host interactions and will help for the early preparation and effective handling of further outbreaks in an ever-changing environment.

Advanced nanoengineered-customized point-of-care tools for prostate-specific antigen.

Change in the level of human prostate-specific antigen (PSA) is a major element in the development and progression of prostate cancer (PCa). Most of the methodologies are currently restricted to their application in routine clinical screening due to the scarcity of adequate screening tools, false reading, long assay time, and cost. Innovative techniques and the integration of knowledge from a variety of domains, such as materials science and engineering, are needed to provide sustainable solutions. The convergence of precision point-of-care (POC) diagnostic techniques, which allow patients to respond in real time to changes in PSA levels, provides promising possibilities for quantitative and quantitative detection of PSA. This solution could be interesting and relevant for use in PCa diagnosis at the POC. The approaches enable low-cost real-time detection and are simple to integrate into user-friendly sensor devices. This review focuses on the investigations, prospects, and challenges associated with integrating engineering sciences with cancer biology to develop nanotechnology-based tools for PCa diagnosis. This article intends to encourage the development of new nanomaterials to construct high-performance POC devices for PCa detection. Finally, the review concludes with closing remarks and a perspective forecast.

Remapping of Adult-Born Neuron Activity during Fear Memory Consolidation in Mice.

The mammalian hippocampal dentate gyrus is a unique memory circuit in which a subset of neurons is continuously generated throughout the lifespan. Previous studies have shown that the dentate gyrus neuronal population can hold fear memory traces (i.e., engrams) and that adult-born neurons (ABNs) support this process. However, it is unclear whether ABNs themselves hold fear memory traces. Therefore, we analyzed ABN activity at a population level across a fear conditioning paradigm. We found that fear learning did not recruit a distinct ABN population. In sharp contrast, a completely different ABN population was recruited during fear memory retrieval. We further provide evidence that ABN population activity remaps over time during the consolidation period. These results suggest that ABNs support the establishment of a fear memory trace in a different manner to directly holding the memory. Moreover, this activity remapping process in ABNs may support the segregation of memories formed at different times. These results provide new insight into the role of adult neurogenesis in the mammalian memory system.

A poly(acrylic acid)-modified copper-organic framework for electrochemical determination of vancomycin.

A copper(II) benzene-1,3,5-tricarboxylate (BTC) metal-organic framework (MOF) was modified with poly(acrylic acid) (PAA) and then used in an electrochemical sensor for vancomycin. The MOF, synthesized via a single-pot method, has enhanced solubility and dispersibility in water as compared to HKUST-1 but without compromising its crystallinity and porosity. The MOF was placed on a glassy carbon electrode (GCE) where it shows enhanced electrocatalytic properties. This is assumed to be due to the presence of the poly(acrylic acid) that forms a network between various HKUST-1 crystals through dimer formation between the carboxy groups of BTC and PAA. This also led to better dispersion of the MOF and to improved interaction between MOF and vancomycin. The structural, spectral and electrochemical properties of the MOFs and their vancomycin complexes was characterized. The modified GCE is shown to be a viable tool for electrochemical determination (best at a working potential of 784 mV vs. Ag/AgCl) of the antibiotic vancomycin in spiked urine and serum samples. Response is linear in the 1-500 nM vancomycin concentration range, and the detection limit is 1 nM, with a relative standard deviation of ±4.3%. Graphical abstractSchematic representation of a method for determination of vancomycin. Poly(acrylic acid) modified HKUST-1 (P-HKUST-1) forms a complex with vancomycin [Van-P-HKUST-1] which is coated over glassy carbon electrode (GCE). The decrease in peak current is recorded as response to vancomycin via cyclic voltammetry.

Curcumin loaded poly (amidoamine) dendrimer-plamitic acid core-shell nanoparticles as anti-stress therapeutics.

Despite poor bioavailability of the drug and in vivo stability, curcumin has been reported for many pharmacological activities. Considering the potential of dendrimers as a drug delivery system, current research work is focused on the formulation and characterization of G4 PAMAM dendrimer-Palmitic acid core-shell nanoparticle-containing curcumin as antistress therapeutics to maximize the bioavailability of curcumin. Various formulations were prepared using different concentrations of palmitic acid and an optimized ratio of dendrimer and curcumin. All formulations were investigated for evaluation of physicochemical parameters, encapsulation efficiency, and in vitro release. Particle size, PDI, zeta-potential, and encapsulation efficiency of final formulation was found to be 257.9 ± 0.365 nm, 0.10 ± 0.004, 3.59 ± 0.167 mV, and 80.87%, respectively. In vitro release studies have shown that 53.62 ± 2.431% of the drug was released after 24 h. In vivo studies pharmacokinetic parameters, drug distribution, pharmacological, and toxicological were also estimated using swiss albino mice. The findings have shown the selected formulation is better than plain curcumin formulation.

Nanomaterial-based optical and electrochemical techniques for detection of methicillin-resistant Staphylococcus aureus: a review.

Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for a number of life-threatening complications in humans. Mutations in the genetic sequence of S. aureus due to the presence of certain genes results in resistance against ß-lactamases. Thus, there is an urgent need for developing highly sensitive techniques for the early detection of MRSA to counter the rise in resistant strains. This review (142 refs.) extensively covers literature reports on nanomaterial-based optical and electrochemical sensors from the year 1983 to date, with particularly emphasis on recent advances in electrochemical sensing (such as voltammetry and impedimetric) and optical sensing (such as colorimetry and fluorometry) techniques. Among the electrochemical methods, various nanomaterials were employed for the modification of electrodes. Whereas, in optical assays, formats such as enzyme linked immunosorbent assay, lateral flow assays or in optical fiber systems are common. In addition, novel sensing platforms are reported by applying advanced nanomaterials which include gold nanoparticles, nanotitania, graphene, graphene-oxide, cadmium telluride and related quantum dots, nanocomposites, upconversion nanoparticles and bacteriophages. Finally, closing remarks and an outlook conclude the review. Graphical abstract Schematic of the diversity of nanomaterial-based methods for detection of methicillin-resistant Staphylococcus aureus (MRSA). AuNPs: gold nanoparticles; QDs: quantum dots; PVL: Panton-Valentine leukocidin; mecA gene: mec-gene complex encoding methicillin resistance.

New perspectives in the topical delivery of optimized amphotericin B loaded nanoemulsions using excipients with innate anti-fungal activities: A mechanistic and histopathological investigation.

This study aimed to develop nanoemulsions (NEs) for the topical delivery of Amphotericin B using lipids and surfactants with innate antifungal activity. NEs were formulated by a slow spontaneous titration method and characterized for particle size, polydispersity index, zeta potential, zone of inhibition (ZOI), in vitro release, enhanced ex vivo rat skin permeation-deposition, hemolysis followed by interaction with the skin using scanning electron microscopy, and histopathology. The ZOI values of the optimized NEs (ANE3) were 21.8±1.5 and 19.7±1.2 mm against A. fumigatus and C. albicans, respectively. The explored excipients and optimized ANE3 elicited hemo-biocompatibility. ANE3 exhibited in vitro sustained release and an enhanced flux value (21.62±1.6 µg/cm2/h) as compared to the drug solution and Fungisome without displaying toxicity. Conclusively, ANE3 could be a promising therapeutic approach with enhanced efficacy and safety for treating a wide range of fungal infections topically.

Electrochemical detection of miRNA using commercial and hand-made screen-printed electrodes: liquid biopsy for cancer management as case of study.

The growth of liquid biopsy, i. e., the possibility of obtaining health information by analysing circulating species (nucleic acids, cells, proteins, and vesicles) in peripheric biofluids, is pushing the field of sensors and biosensors beyond the limit to provide decentralised solutions for nonspecialists. In particular, among all the circulating species that can be adopted in managing cancer evolution, both for diagnostic and prognostic applications, microRNAs have been highly studied and detected. The development of electrochemical devices is particularly relevant for liquid biopsy purposes, and the screen-printed electrodes (SPEs) represent one of the building blocks for producing novel portable devices. In this work, we have taken miR-2115-3p as model target (it is related to lung cancer), and we have developed a biosensor by exploiting the use of a complementary DNA probe modified with methylene blue as redox mediator. In particular, the chosen sensing architecture was applied to serum measurements of the selected miRNA, obtaining a detection limit within the low nanomolar range; in addition, various platforms were interrogated, namely commercial and hand-made SPEs, with the aim of providing the reader with some insights about the optimal platform to be used by considering both the cost and the analytical performance.

Technical Evaluation of a Paper-Based Electrochemical Strip to Measure Nitrite Ions in the Forensic Field.

Nitrite is a compound used as a food additive for its preservative action and coloring capability, as well as an industrial agent for its antifreezing action and for preventing corrosion, and it is also used as a pharmaceutical in cyanide detoxification therapy. However, even recently, because of its high toxicity, it has been used as a murder and suicidal agent due to its affordability and ready availability. In this technical report, we describe an electrochemical paper-based device for selectively determining nitrite in complex biofluids, such as blood, cadaveric blood, vitreous humor, serum, plasma, and urine. The approach was validated in terms of the linearity of response, selectivity, and sensitivity, and the accuracy of the determination was verified by comparing the results with a chromatographic instrumental method. A linear response was observed in the micromolar range; the sensitivity of the method expressed as the limit of detection was 0.4 µM in buffer measurements. The simplicity of use, the portability of the device, and the performance shown make the approach suitable for detecting nitrite in complex biofluids, including contexts of forensic interest, such as murders or suicides in which nitrite is used as a toxic agent. Limits of detection of ca. 1, 2, 4, 5, 3, and 4 µM were obtained in vitreous humor, urine, serum and plasma, blood, and cadaveric blood, also highlighting a satisfactory accuracy comprised between 91 and 112%.

RETRACTED: Aldawsari et al. Gum Acacia Functionalized Colloidal Gold Nanoparticles of Letrozole as Biocompatible Drug Delivery Carrier for Treatment of Breast Cancer. Pharmaceutics 2021, 13, 1554.

The Pharmaceutics Editorial Office retracts the article, "Gum Acacia Functionalized Colloidal Gold Nanoparticles of Letrozole as Biocompatible Drug Delivery Carrier for Treatment of Breast Cancer" [...].

Paper-based electrochemical device for early detection of integrin αvß6 expressing tumors.

Despite progress in the prevention and diagnosis of cancer, current technologies for tumor detection present several limitations including invasiveness, toxicity, inaccuracy, lengthy testing duration and high cost. Therefore, innovative diagnostic techniques that integrate knowledge from biology, oncology, medicinal and analytical chemistry are now quickly emerging in the attempt to address these issues. Following this approach, here we developed a paper-based electrochemical device for detecting cancer-derived Small Extracellular Vesicles (S-EVs) in fluids. S-EVs were obtained from cancer cell lines known to express, at a different level, the αvß6 integrin receptor, a well-established hallmark of numerous epithelial cancer types. The resulting biosensor turned out to recognize αvß6-containing S-EVs down to a limit of 0.7*103 S-EVs/mL with a linear range up to 105 S-EVs /mL, and a relative standard deviation of 11%, thus it may represent a novel opportunity for αvß6 expressing cancers detection.

Novel Approaches to Enzyme-Based Electrochemical Nanobiosensors.

Electrochemistry is a genuinely interdisciplinary science that may be used in various physical, chemical, and biological domains. Moreover, using biosensors to quantify biological or biochemical processes is critical in medical, biological, and biotechnological applications. Nowadays, there are several electrochemical biosensors for various healthcare applications, such as for the determination of glucose, lactate, catecholamines, nucleic acid, uric acid, and so on. Enzyme-based analytical techniques rely on detecting the co-substrate or, more precisely, the products of a catalyzed reaction. The glucose oxidase enzyme is generally used in enzyme-based biosensors to measure glucose in tears, blood, etc. Moreover, among all nanomaterials, carbon-based nanomaterials have generally been utilized thanks to the unique properties of carbon. The sensitivity can be up to pM levels using enzyme-based nanobiosensor, and these sensors are very selective, as all enzymes are specific for their substrates. Furthermore, enzyme-based biosensors frequently have fast reaction times, allowing for real-time monitoring and analyses. These biosensors, however, have several drawbacks. Changes in temperature, pH, and other environmental factors can influence the stability and activity of the enzymes, affecting the reliability and repeatability of the readings. Additionally, the cost of the enzymes and their immobilization onto appropriate transducer surfaces might be prohibitively expensive, impeding the large-scale commercialization and widespread use of biosensors. This review discusses the design, detection, and immobilization techniques for enzyme-based electrochemical nanobiosensors, and recent applications in enzyme-based electrochemical studies are evaluated and tabulated.

Reviewing the state of biosensors and lab-on-a- chip technologies: opportunities for extreme environments and space exploration.

The space race is entering a new era of exploration, in which the number of robotic and human missions to various places in our solar system is rapidly increasing. Despite the recent advances in propulsion and life support technologies, there is a growing need to perform analytical measurements and laboratory experiments across diverse domains of science, while keeping low payload requirements. In this context, lab-on-a-chip nanobiosensors appear to be an emerging technology capable of revolutionizing space exploration, given their low footprint, high accuracy, and low payload requirements. To date, only some approaches for monitoring astronaut health in spacecraft environments have been reported. Although non-invasive molecular diagnostics, like lab-on-a-chip technology, are expected to improve the quality of long-term space missions, their application to monitor microbiological and environmental variables is rarely reported, even for analogous extreme environments on Earth. The possibility of evaluating the occurrence of unknown or unexpected species, identifying redox gradients relevant to microbial metabolism, or testing for specific possible biosignatures, will play a key role in the future of space microbiology. In this review, we will examine the current and potential roles of lab-on-a-chip technology in space exploration and in extreme environment investigation, reporting what has been tested so far, and clarifying the direction toward which the newly developed technologies of portable lab-on-a-chip sensors are heading for exploration in extreme environments and in space.

Current understanding, challenges and perspective on portable systems applied to plant monitoring and precision agriculture.

The devastating effects of global climate change on crop production and exponential population growth pose a major challenge to agricultural yields. To cope with this problem, crop performance monitoring is becoming increasingly necessary. In this scenario, the use of sensors and biosensors capable of detecting changes in plant fitness and predicting the evolution of their morphology and physiology has proven to be a useful strategy to increase crop yields. Flexible sensors and nanomaterials have inspired the emerging fields of wearable and on-plant portable devices that provide continuous and accurate long-term sensing of morphological, physiological, biochemical, and environmental parameters. This review provides an overview of novel plant sensing technologies by discussing wearable and integrated devices proposed for engineering plant and monitoring its morphological traits and physiological processes, as well as plant-environment interactions. For each application scenario, the state-of-the-art sensing solutions are grouped according to the plant organ on which they have been installed highlighting their main technological advantages and features. Finally, future opportunities, challenges and perspectives are discussed. We anticipate that the application of this technology in agriculture will provide more accurate measurements for farmers and plant scientists with the ability to track crop performance in real time. All of this information will be essential to enable rapid optimization of plants development through tailored treatments that improve overall plant health even under stressful conditions, with the ultimate goal of increasing crop productivity in a more sustainable manner.

Electrochemical nano biosensors for the detection of extracellular vesicles exosomes: From the benchtop to everywhere?

Detection of extracellular vesicles (EVs) exosomes is a challenge to address the need for better diagnostic tests and to create a point-of-care (POC) platform that can detect, monitor and treat health conditions early to allow personalized therapies. A multidisciplinary approach is needed to address these health-related technical issues. Over the past decade, materials scientists and engineers have worked on the same platform to develop flexible, lightweight, miniaturized, and integrated POC devices for exosome detection. Therefore, exosome detection based on various nanomaterials is of particular interest. In this paper, we describe the current state of knowledge on 0D-3D nanostructured materials and present a POC-based technique for exosome detection. Finally, the challenges that need to be solved to expand their clinical application are discussed.

Tailored point-of-care biosensors for liquid biopsy in the field of oncology.

In the field of cancer detection, technologies to analyze tumors using biomarkers circulating in fluids such as blood have developed rapidly based on liquid biopsy. A proactive approach to early cancer detection can lead to more effective treatments with minimal side effects and better long-term patient survival. However, early detection of cancer is hindered by the existing limitations of conventional cancer diagnostic methods. To enable early diagnosis and regular monitoring and improve automation, the development of integrated point-of-care (POC) and biosensors is needed. This is expected to fundamentally change the diagnosis, management, and monitoring of response to treatment of cancer. POC-based techniques will provide a way to avoid complications that occur after invasive tissue biopsy, such as bleeding, infection, and pain. The aim of this study is to provide a comprehensive view of biosensors and their clinical relevance in oncology for the detection of biomarkers with liquid biopsies of proteins, miRNA, ctDNA, exosomes, and cancer cells. The preceding discussion also illustrates the changing landscape of liquid biopsy-based cancer diagnosis through nanomaterials, machine learning, artificial intelligence, wearable devices, and sensors, many of which apply POC design principles. With the advent of sensitive, selective, and timely detection of cancer, we see the field of POC technology for cancer detection and treatment undergoing a positive paradigm shift in the foreseeable future.