Classification and application of metal-based nanoantioxidants in medicine and healthcare.

Antioxidants play an important role in the prevention of oxidative stress and have been widely used in medicine and healthcare. However, natural antioxidants have several limitations such as low stability, difficult long-term storage, and high cost of large-scale production. Along with significant advances in nanotechnology, nanomaterials have emerged as a promising solution to improve the limitations of natural antioxidants because of their high stability, easy storage, time effectiveness, and low cost. Among various types of nanomaterials exhibiting antioxidant activity, metal-based nanoantioxidants show excellent reactivity because of the presence of an unpaired electron in their atomic structure. In this review, we summarize some novel metal-based nanoantioxidants and classify them into two main categories, namely chain-breaking and preventive antioxidant nanomaterials. In addition, the applications of antioxidant nanomaterials in medicine and healthcare are also discussed. This review provides a deeper understanding of the mechanisms of metal-based nanoantioxidants and a guideline for using these nanomaterials in medicine and healthcare.

Pipette-free field-deployable molecular diagnostic kit for bimodal visual detection of infectious RNA viruses.

Here, we developed a field-deployable molecular diagnostic kit for the detection of RNA viruses that operates in a pipette-free manner. The kit is composed of acrylic sticks, PCR tubes, and palm-sized three-dimensional(3D)-printed heaters operated by batteries. The kit performs RNA extraction, reverse transcriptase loop-mediated isothermal amplification (RT-LAMP), and visual detection in one kit. An acrylic stick was engraved with one shallow and one deep cylindrical chamber at each end for the insertion of an FTA card and ethidium homodimer-1 (EthD-1), respectively, to perform RNA extraction/purification and bimodal visual detection of the target amplicons. First, an intercalation of EthD-1 into the target DNA initially produces fluorescence upon UV illumination. Next, the addition of a strong oxidant, in this case sodium (meta) periodate (NaIO4 ), produces intense aggregates in the presence of EthD-1-intercalated DNA, realized by electrostatic interaction. In the absence of the target amplicon, no fluorescence or aggregates are observed. Using this kit, two major infectious viruses-severe fever with thrombocytopenia syndrome virus (SFTSV) and severe acute respiratory syndrome coronavirus (SARS-CoV-2)-were successfully detected in 1 h, and the limits of detection (LOD) were approximately 1 virus µL-1 for SFTSV and 103 copies µL-1 for SARS-CoV-2 RNA. The introduced kit is portable, end-user-friendly, and can be operated in a pipette-free manner, paving the way for simple and convenient virus detection in resource-limited settings.

Microfluidic advances in food safety control.

Food contamination is a global concern, particularly in developing countries. Two main types of food contaminants-chemical and biological-are common problems that threaten human health. Therefore, rapid and accurate detection methods are required to address the threat of food contamination. Conventional methods employed to detect these two types of food contaminants have several limitations, including high costs and long analysis time. Alternatively, microfluidic technology, which allows for simple, rapid, and on-site testing, can enable us to control food safety in a timely, cost-effective, simple, and accurate manner. This review summarizes advances in microfluidic approaches to detect contaminants in food. Different detection methods have been applied to microfluidic platforms to identify two main types of contaminants: chemical and biological. For chemical contaminant control, the application of microfluidic approaches for detecting heavy metals, pesticides, antibiotic residues, and other contaminants in food samples is reviewed. Different methods including enzymatic, chemical-based, immunoassay-based, molecular-based, and electrochemical methods for chemical contaminant detection are discussed based on their working principle, the integration in microfluidic platforms, advantages, and limitations. Microfluidic approaches for foodborne pathogen detection, from sample preparation to final detection, are reviewed to identify foodborne pathogens. Common methods for foodborne pathogens screening, namely immunoassay, nucleic acid amplification methods, and other methods are listed and discussed; highlighted examples of recent studies are also reviewed. Challenges and future trends that could be employed in microfluidic design and fabrication process to address the existing limitations for food safety control are also covered. Microfluidic technology is a promising tool for food safety control with high efficiency and applicability. Miniaturization, portability, low cost, and samples and reagents saving make microfluidic devices an ideal choice for on-site detection, especially in low-resource areas. Despite many advantages of microfluidic technology, the wide manufacturing of microfluidic devices still demands intensive studies to be conducted for user-friendly and accurate food safety control. Introduction of recent advances of microfluidic devices will build a comprehensive understanding of the technology and offer comparative analysis for future studies and on-site application.

Microfluidic Formulation for Biomedical Applications.

Microfluidic technology was recognized in the 1980s when the first micropumps and micro-valves were developed to manipulate fluids for biological applications [...].

Chitosan: a green adhesive for surface functionalization and fabrication of thermoplastic biomedical microdevices.

Chitosan (CS) is a natural polymer that exhibits many biological properties and is used as a biomaterial for antibacterial coatings, tissue engineering, cell research, drug delivery, and negatively charged molecule capture. In our previous study, we used a CS-polydopamine mixture to realize UV-assisted bonding between poly(methyl methacrylate) (PMMA) substrates to fabricate microdevices for self-assembled stem cell spheroid cultures. Herein, we attained reliable adhesive bonding between PMMAs using CS at room temperature assisted by oxygen plasma. The bond strength of adhesion was as high as 2.1 MPa, which could be stable for over two months according to the leak test. The adhesive bonding and surface functionalization of the microchannels were simultaneously completed such that the microdevices could be directly used for mesenchymal stem cell culture for spheroid generation and DNA purification for point-of-care testing (POCT) devices. Surface characterization was performed by contact angle measurements, Fourier-transform infrared spectroscopy, scanning electron microscopy, and atomic force microscopy. The POCT device allows sequential on-chip DNA purification, amplification, and colorimetric detection of pathogenic bacteria. This method provides a convenient and reliable strategy for the fabrication of PMMA microdevices that can be directly implemented in biological studies and POCT applications without involving prior surface modification steps.

Droplet-Based Microfluidics: Applications in Pharmaceuticals.

Droplet-based microfluidics offer great opportunities for applications in various fields, such as diagnostics, food sciences, and drug discovery. A droplet provides an isolated environment for performing a single reaction within a microscale-volume sample, allowing for a fast reaction with a high sensitivity, high throughput, and low risk of cross-contamination. Owing to several remarkable features, droplet-based microfluidic techniques have been intensively studied. In this review, we discuss the impact of droplet microfluidics, particularly focusing on drug screening and development. In addition, we surveyed various methods of device fabrication and droplet generation/manipulation. We further highlight some promising studies covering drug synthesis and delivery that were updated within the last 5 years. This review provides researchers with a quick guide that includes the most up-to-date and relevant information on the latest scientific findings on the development of droplet-based microfluidics in the pharmaceutical field.

Antioxidant Nanozymes: Mechanisms, Activity Manipulation, and Applications.

Antioxidant enzymes such as catalase, superoxide dismutase, and glutathione peroxidase play important roles in the inhibition of oxidative-damage-related pathological diseases. However, natural antioxidant enzymes face some limitations, including low stability, high cost, and less flexibility. Recently, antioxidant nanozymes have emerged as promising materials to replace natural antioxidant enzymes for their stability, cost savings, and flexible design. The present review firstly discusses the mechanisms of antioxidant nanozymes, focusing on catalase-, superoxide dismutase-, and glutathione peroxidase-like activities. Then, we summarize the main strategies for the manipulation of antioxidant nanozymes based on their size, morphology, composition, surface modification, and modification with a metal-organic framework. Furthermore, the applications of antioxidant nanozymes in medicine and healthcare are also discussed as potential biological applications. In brief, this review provides useful information for the further development of antioxidant nanozymes, offering opportunities to improve current limitations and expand the application of antioxidant nanozymes.

Recent Advances in Molecular and Immunological Diagnostic Platform for Virus Detection: A Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an ongoing coronavirus disease (COVID-19) outbreak and a rising demand for the development of accurate, timely, and cost-effective diagnostic tests for SARS-CoV-2 as well as other viral infections in general. Currently, traditional virus screening methods such as plate culturing and real-time PCR are considered the gold standard with accurate and sensitive results. However, these methods still require sophisticated equipment, trained personnel, and a long analysis time. Alternatively, with the integration of microfluidic and biosensor technologies, microfluidic-based biosensors offer the ability to perform sample preparation and simultaneous detection of many analyses in one platform. High sensitivity, accuracy, portability, low cost, high throughput, and real-time detection can be achieved using a single platform. This review presents recent advances in microfluidic-based biosensors from many works to demonstrate the advantages of merging the two technologies for sensing viruses. Different platforms for virus detection are classified into two main sections: immunoassays and molecular assays. Moreover, available commercial sensing tests are analyzed.

Design Strategy and Application of Deep Eutectic Solvents for Green Synthesis of Nanomaterials.

The first report of deep eutectic solvents (DESs) was released in 2003 and was identified as a new member of ionic liquid (IL), involving innovative chemical and physical characteristics. Using green solvent technology concerning economical, practical, and environmental aspects, DESs open the window for sustainable development of nanomaterial fabrication. The DESs assist in different fabrication processes and design nanostructures with specific morphology and properties by tunable reaction conditions. Using DESs in synthesis reactions can reduce the required high temperature and pressure conditions for decreasing energy consumption and the risk of environmental contamination. This review paper provides the recent applications and advances in the design strategy of DESs for the green synthesis of nanomaterials. The strategy and application of DESs in wet-chemical processes, nanosize reticular material fabrication, electrodeposition/electrochemical synthesis of nanostructures, electroless deposition, DESs based nano-catalytic and nanofluidic systems are discussed and highlighted in this review.

Recent Progress in Nanotechnology-Based Approaches for Food Monitoring.

Throughout the food supply chain, including production, storage, and distribution, food can be contaminated by harmful chemicals and microorganisms, resulting in a severe threat to human health. In recent years, the rapid advancement and development of nanotechnology proposed revolutionary solutions to solve several problems in scientific and industrial areas, including food monitoring. Nanotechnology can be incorporated into chemical and biological sensors to improve analytical performance, such as response time, sensitivity, selectivity, reliability, and accuracy. Based on the characteristics of the contaminants and the detection methods, nanotechnology can be applied in different ways in order to improve conventional techniques. Nanomaterials such as nanoparticles, nanorods, nanosheets, nanocomposites, nanotubes, and nanowires provide various functions for the immobilization and labeling of contaminants in electrochemical and optical detection. This review summarizes the recent advances in nanotechnology for detecting chemical and biological contaminations in the food supply chain.

Sensors for Detection of the Synthetic Dye Rhodamine in Environmental Monitoring Based on SERS.

This article presents a review of many types of SERS sensors for food safety and environmental pollution monitoring based on detecting rhodamine. It introduces the basic concepts of substrates, enhancement factors, and mechanisms, devices' sensors integrated with the microstructure. Here, we review the state-of-the-art research in the field of rhodamine monitoring and highlight the applications of SERS sensors. The trends in the development of substrates for different applications have been mentioned with the aim of providing an overview of the development of different SERS substrates. Thus, an efficient approach for rhodamine detection has a good perspective for application in environmental monitoring.

Bonding Strategies for Thermoplastics Applicable for Bioanalysis and Diagnostics.

Microfluidics is a multidisciplinary science that includes physics, chemistry, engineering, and biotechnology. Such microscale systems are receiving growing interest in applications such as analysis, diagnostics, and biomedical research. Thermoplastic polymers have emerged as one of the most attractive materials for microfluidic device fabrication owing to advantages such as being optically transparent, biocompatible, cost-effective, and mass producible. However, thermoplastic bonding is a key challenge for sealing microfluidic devices. Given the wide range of bonding methods, the appropriate bonding approach should be carefully selected depending on the thermoplastic material and functional requirements. In this review, we aim to provide a comprehensive overview of thermoplastic fabricating and bonding approaches, presenting their advantages and disadvantages, to assist in finding suitable microfluidic device bonding methods. In addition, we highlight current applications of thermoplastic microfluidics to analyses and diagnostics and introduce future perspectives on thermoplastic bonding strategies.

Recent Methods for the Viability Assessment of Bacterial Pathogens: Advances, Challenges, and Future Perspectives.

Viability assessment is a critical step in evaluating bacterial pathogens to determine infectious risks to public health. Based on three accepted viable criteria (culturability, metabolic activity, and membrane integrity), current viability assessments are categorized into three main strategies. The first strategy relies on the culturability of bacteria. The major limitation of this strategy is that it cannot detect viable but nonculturable (VBNC) bacteria. As the second strategy, based on the metabolic activity of bacteria, VBNC bacteria can be detected. However, VBNC bacteria sometimes can enter a dormant state that allows them to silence reproduction and metabolism; therefore, they cannot be detected based on culturability and metabolic activity. In order to overcome this drawback, viability assessments based on membrane integrity (third strategy) have been developed. However, these techniques generally require multiple steps, bulky machines, and laboratory technicians to conduct the tests, making them less attractive and popular applications. With significant advances in microfluidic technology, these limitations of current technologies for viability assessment can be improved. This review summarized and discussed the advances, challenges, and future perspectives of current methods for the viability assessment of bacterial pathogens.

Fabrication of Wearable PDMS Device for Rapid Detection of Nucleic Acids via Recombinase Polymerase Amplification Operated by Human Body Heat.

Pathogen detection by nucleic acid amplification proved its significance during the current coronavirus disease 2019 (COVID-19) pandemic. The emergence of recombinase polymerase amplification (RPA) has enabled nucleic acid amplification in limited-resource conditions owing to the low operating temperatures around the human body. In this study, we fabricated a wearable RPA microdevice using poly(dimethylsiloxane) (PDMS), which can form soft-but tight-contact with human skin without external support during the body-heat-based reaction process. In particular, the curing agent ratio of PDMS was tuned to improve the flexibility and adhesion of the device for better contact with human skin, as well as to temporally bond the microdevice without requiring further surface modification steps. For PDMS characterization, water contact angle measurements and tests for flexibility, stretchability, bond strength, comfortability, and bendability were conducted to confirm the surface properties of the different mixing ratios of PDMS. By using human body heat, the wearable RPA microdevices were successfully applied to amplify 210 bp from Escherichia coli O157:H7 (E. coli O157:H7) and 203 bp from the DNA plasmid SARS-CoV-2 within 23 min. The limit of detection (LOD) was approximately 500 pg/reaction for genomic DNA template (E. coli O157:H7), and 600 fg/reaction for plasmid DNA template (SARS-CoV-2), based on gel electrophoresis. The wearable RPA microdevice could have a high impact on DNA amplification in instrument-free and resource-limited settings.

Microfluidic Biosensors for Point-of-Care Nucleic Acid Amplification Tests.

This Special Issue of Biosensors, "Microfluidic Biosensors for Point-of-Care Nucleic Acid Amplification Tests" aims to gather original research papers and comprehensive reviews detailing novel research, fabrication methods, and applications, as well as the challenges and prospects of developing microfluidics for improved biosensing and diagnostics [...].

Pressure-Free Assembling of Poly(methyl methacrylate) Microdevices via Microwave-Assisted Solvent Bonding and Its Biomedical Applications.

Poly(methyl methacrylate) (PMMA) has become an appealing material for manufacturing microfluidic chips, particularly for biomedical applications, because of its transparency and biocompatibility, making the development of an appropriate bonding strategy critical. In our research, we used acetic acid as a solvent to create a pressure-free assembly of PMMA microdevices. The acetic acid applied between the PMMA slabs was activated by microwave using a household microwave oven to tightly merge the substrates without external pressure such as clamps. The bonding performance was tested and a superior bond strength of 14.95 ± 0.77 MPa was achieved when 70% acetic acid was used. Over a long period, the assembled PMMA device with microchannels did not show any leakage. PMMA microdevices were also built as a serpentine 2D passive micromixer and cell culture platform to demonstrate their applicability. The results demonstrated that the bonding scheme allows for the easy assembly of PMMAs with a low risk of clogging and is highly biocompatible. This method provides for a simple but robust assembly of PMMA microdevices in a short time without requiring expensive instruments.

Development of a highly sensitive sensor chip using optical diagnostic based on functionalized plasmonically active AuNPs.

Measuring solution concentration plays an important role in chemical, biochemical, clinical diagnosis, environmental monitoring, and biological analyses. In this work, we develop a transmission-mode localized surface plasmon resonance sensor chip system and convenient method which is highly efficient, highly sensitive for detection sensing using multimode fiber. The plasmonically active sensor's surface AuNPs with high-density NPs were decorated onto 1 cm sensing length of various clad-free fiber in the form of homogeneous monolayer utilizing a self-assembly process for immobilization of the target molecule. The carboxyl bond is formed through a functional reaction on the sensor head. Using the significance in the refractive index difference and numerical aperture, which is caused by a variation in the concentration of measuring bovine serum albumin (BSA) protein which can be accurately measured by the output signal. The refractive index variation of the medium analyte layer can be converted to signal output power change at the He-Ne wavelength of 632.8 nm. The sensor detection limit was estimated to be 0.075 ng ml-1for BSA protein which shows high sensitivity compared to other types of label-free optical biosensors. This also leads to a possibility of finding the improvement in the sensitivity label-free biosensors. The conventional method should allow multimode fiber biosensors to become a possible replacement for conventional biosensing techniques based on fluorescence.

Metal-enhanced sensing platform for the highly sensitive detection of C-reactive protein antibody and rhodamine B with applications in cardiovascular diseases and food safety.

The potential applications of metal-enhanced fluorescence (MEF) devices include biosensors for the detection of trace amounts in biosciences, biotechnology, and pathogens that are relevant to medical diagnostics and food control. In the present study, the silver (Ag) film thickness (56 nm) of an MEF system was calibrated to maximize the depth-to-width ratio (Γ) of the surface plasmon resonance (SPR) active metal from reflectance dip curves. Upon plasmon coupling with thermally evaporated Ag, we demonstrated a 2.21-fold enhancement compared to the pristine flat substrate with the coefficient of variation (CV) ≈0.22% and the limit of detection (LOD) 0.001 mg L-1 of the concentration of an Alexa Fluor 488-labeled anti-C-reactive protein antibody (CRP@Alexa fluor 488). The structure was developed to simplify the in situ generation of biosensors for the surface-enhanced Raman spectroscopy (SERS) to determine Rhodamine B (RhB) with a highly robust performance. The procedure presented a simple and rapid sample pretreatment for the determination of RhB with a limit of quantification of 10-10 M and a satisfactory linear response (0.98). The results showed the excellent performance of the surface plasmon coupled emission (SPCE), which opens up possibilities for the accurate detection of small-volume and low-concentration target analytes due to the improved sensitivity and signal-to-noise ratio (SNR).

Poly(acrylic acid) as an adhesion promoter for UV-assisted thermoplastic bonding: Application for the in vitro construction of human blood vessels.

In this study, we introduced a novel adhesion bonding method for fabricating thermoplastic microdevices using poly(acrylic acid) (PAA) as a UV-assisted adhesion promoter. The bonding mechanism was based on the covalent cross-links between poly(methyl methacrylate) (PMMA) and PAA via the free radicals in their carbon backbone generated under UV irradiation. The water contact angle and Fourier-transformed infrared (FTIR) analysis were performed to analyze the surface characteristics of the PAA-coated PMMA. PMMAs were bonded under UV treatment for 60 s with the highest bond strength of around 1.18 MPa. The PMMA microdevice was leak-proof for over 200 h. Besides, clog-free PMMA microdevices with various-sizes microchannels were performed to demonstrate such a high applicable bonding method for microdevice fabrication. Moreover, PMMAs were bonded with other thermoplastics with a bond strength of around 0.5 MPa. Notably, collagen was easily coated inside the PMMA microchannels via electrostatic interaction between PAA and collagen which is beneficial for on-device cell culture. As a result, a layered co-culture model of smooth muscle cells (SMCs) and human umbilical vein endothelial cells (HUVECs) was realized inside simple straight microchannels mimicking human blood vessel wall. Therefore, the introduced bonding method could pave the way for fabricating microdevice for cell-related applications.

Chitosan-polydopamine hydrogel complex: a novel green adhesion agent for reversibly bonding thermoplastic microdevice and its application for cell-friendly microfluidic 3D cell culture.

Owing to biocompatible characteristics and supporting cell growth capability, hydrogels have been widely used for scaffold fabrication and surface coating for cell culture. To employ the advantages of hydrogels, in the present study, we introduce a biocompatible chitosan (CS)-polydopamine (pDA) hydrogel complex as a green adhesion agent for the reversible bonding of thermoplastics assisted by UV irradiation. Poly(methyl methacrylate) (PMMA) substrates were bonded due to the covalent bond network formed between the amine groups of either CS or pDA in the hydrogel complex and the aldehyde groups of the oxidized PMMA surface via the Schiff-base reaction during the UV irradiation. Furthermore, the introduced method allowed for reversible bonding, which is highly appropriate for the fabrication of microdevices for cell-related applications. Surface characterizations such as water contact angle measurement, scanning electron microscopy analysis (SEM), atomic force microscopy analysis (AFM), and Fourier-transform infrared microscopy analysis (FTIR) were performed to confirm the successful coating of the hydrogel complex on the PMMA surface. Moreover, the bonding between two PMMAs or PMMA with other thermoplastics was successfully investigated with high bond strengths ranging from 0.4 to 0.7 MPa. The potential for reversible bonding of this method was verified by repeating the bonding/debonding cycle of the bonded PMMAs for three times, which maintained the bond strength at approximately 0.5 MPa. The compatibility of the bonding method in biological applications was examined by culturing mesenchymal stem cells (MSCs) inside a microchannel where multiple uniform-sized MSC spheroids were successfully formed. Then, spheroids were harvested for off-chip experiments enabled by the reversibility of the introduced bonding strategy. The bonding strategy employing a green hydrogel complex as a cell-friendly and eco-friendly adhesion agent could have a high impact on the fabrication of microdevices suitable for advanced organ-on-a-chip studies.