Nanomaterials for Healthcare Biosensing Applications

In recent years, an increasing number of nanomaterials have been explored for their applications in biomedical diagnostics, making their applications in healthcare biosensing a rapidly evolving field. Nanomaterials introduce versatility to the sensing platforms and may even allow mobility between different detection mechanisms. The prospect of a combination of different nanomaterials allows an exploitation of their synergistic additive and novel properties for sensor development. This paper covers more than 290 research works since 2015, elaborating the diverse roles played by various nanomaterials in the biosensing field. Hence, we provide a comprehensive review of the healthcare sensing applications of nanomaterials, covering carbon allotrope-based, inorganic, and organic nanomaterials. These sensing systems are able to detect a wide variety of clinically relevant molecules, like nucleic acids, viruses, bacteria, cancer antigens, pharmaceuticals and narcotic drugs, toxins, contaminants, as well as entire cells in various sensing media, ranging from buffers to more complex environments such as urine, blood or sputum. Thus, the latest advancements reviewed in this paper hold tremendous potential for the application of nanomaterials in the early screening of diseases and point-of-care testing

Recent Progress in Optical Sensors for Biomedical Diagnostics

In recent years, several types of optical sensors have been probed for their aptitude in healthcare biosensing, making their applications in biomedical diagnostics a rapidly evolving subject. Optical sensors show versatility amongst different receptor types and even permit the integration of different detection mechanisms. Such conjugated sensing platforms facilitate the exploitation of their neoteric synergistic characteristics for sensor fabrication. This paper covers nearly 250 research articles since 2016 representing the emerging interest in rapid, reproducible and ultrasensitive assays in clinical analysis. Therefore, we present an elaborate review of biomedical diagnostics with the help of optical sensors working on varied principles such as surface plasmon resonance, localised surface plasmon resonance, evanescent wave fluorescence, bioluminescence and several others. These sensors are capable of investigating toxins, proteins, pathogens, disease biomarkers and whole cells in varied sensing media ranging from water to buffer to more complex environments such as serum, blood or urine. Hence, the recent trends discussed in this review hold enormous potential for the widespread use of optical sensors in early-stage disease prediction and point-of-care testing devices.DFG, 428780268, Biomimetische Rezeptoren auf NanoMIP-Basis zur Virenerkennung und -entfernung mittels integrierter Ansätz

Applications of Graphene Quantum Dots in Biomedical Sensors

Due to the proliferative cancer rates, cardiovascular diseases, neurodegenerative disorders, autoimmune diseases and a plethora of infections across the globe, it is essential to introduce strategies that can rapidly and specifically detect the ultralow concentrations of relevant biomarkers, pathogens, toxins and pharmaceuticals in biological matrices. Considering these pathophysiologies, various research works have become necessary to fabricate biosensors for their early diagnosis and treatment, using nanomaterials like quantum dots (QDs). These nanomaterials effectively ameliorate the sensor performance with respect to their reproducibility, selectivity as well as sensitivity. In particular, graphene quantum dots (GQDs), which are ideally graphene fragments of nanometer size, constitute discrete features such as acting as attractive fluorophores and excellent electro-catalysts owing to their photo-stability, water-solubility, biocompatibility, non-toxicity and lucrativeness that make them favorable candidates for a wide range of novel biomedical applications. Herein, we reviewed about 300 biomedical studies reported over the last five years which entail the state of art as well as some pioneering ideas with respect to the prominent role of GQDs, especially in the development of optical, electrochemical and photoelectrochemical biosensors. Additionally, we outline the ideal properties of GQDs, their eclectic methods of synthesis, and the general principle behind several biosensing techniques.DFG, 428780268, Biomimetische Rezeptoren auf NanoMIP-Basis zur Virenerkennung und -entfernung mittels integrierter Ansätz

Graphene Quantum Dot-Based Electrochemical Immunosensors for Biomedical Applications

In the area of biomedicine, research for designing electrochemical sensors has evolved over the past decade, since it is crucial to selectively quantify biomarkers or pathogens in clinical samples for the efficacious diagnosis and/or treatment of various diseases. To fulfil the demand of rapid, specific, economic, and easy detection of such biomolecules in ultralow amounts, numerous nanomaterials have been explored to effectively enhance the sensitivity, selectivity, and reproducibility of immunosensors. Graphene quantum dots (GQDs) have garnered tremendous attention in immunosensor development, owing to their special attributes such as large surface area, excellent biocompatibility, quantum confinement, edge effects, and abundant sites for chemical modification. Besides these distinct features, GQDs acquire peroxidase (POD)-mimicking electro-catalytic activity, and hence, they can replace horseradish peroxidase (HRP)-based systems to conduct facile, quick, and inexpensive label-free immunoassays. The chief motive of this review article is to summarize and focus on the recent advances in GQD-based electrochemical immunosensors for the early and rapid detection of cancer, cardiovascular disorders, and pathogenic diseases. Moreover, the underlying principles of electrochemical immunosensing techniques are also highlighted. These GQD immunosensors are ubiquitous in biomedical diagnosis and conducive for miniaturization, encouraging low-cost disease diagnostics in developing nations using point-of-care testing (POCT) and similar allusive techniques.TU Berlin, Open-Access-Mittel - 201

Surface plasmon resonance based sensor for the detection of glycopeptide antibiotics in milk using rationally designed nanoMIPs

Glycopeptide antibiotics are known as the last resort for the treatment of serious infections caused by Gram-positive bacteria. The use of milk products contaminated with these antibiotic residues leads to allergic reactions and sensitivity in human. Also, long-term consumption of milk products containing low levels of these antibiotics may cause the relevant bacteria to build up resistance to these last resort antibiotics. Sensitive, rapid and effective quantification and monitoring systems play a key role for their determination in milk products. Hence, molecularly imprinted nanostructures were rationally designed in this work to produce high affinity synthetic receptors to be coupled with a surface plasmon resonance sensor for the analysis of glycopeptide antibiotics in milk samples. The nanoMIP-SPR sensor enabled vancomycin quantification with the LODs of 4.1 ng mL−1 and 17.7 ng mL−1 using direct and competitive assays, respectively. The recoveries rates for two sensor methods ranged in 85–110% with RSDs below 7%. The affinity between the nanoMIP receptors and the target molecule (dissociation constant: 1.8 × 10−9 M) is mostly superior to natural receptors and other synthetic receptors. Unlike other methods commonly employed for the detection of milk contaminants this approach is extremely simple, fast and robust, and do not require pre-sample treatment.DFG, 325093850, Open Access Publizieren 2017 - 2018 / Technische Universität Berli

Graphene Quantum Dots as Nanozymes for Electrochemical Sensing of Yersinia enterocolitica in Milk and Human Serum

The genus Yersinia contains three well-recognized human pathogens, including Y. enterocolitica, Y. pestis, and Y. pseudotuberculosis. Various domesticated and wild animals carry Yersinia in their intestines. Spread to individuals arises from eating food or water contaminated by infected human or animal faeces. Interaction with infected pets and domestic stock may also lead to infection. Yersinia is able to multiply at temperatures found in normal refrigerators; hence, a large number of the bacteria may be present if meat is kept without freezing. Yersinia is also rarely transmitted by blood transfusion, because it is able to multiply in stored blood products. Infection with Yersinia can cause yersiniosis, a serious bacterial infection associated with fever, abdominal pain and cramps, diarrhea, joint pain, and symptoms similar to appendicitis in older children and adults. This paper describes a novel immunosensor approach using graphene quantum dots (GQDs) as enzyme mimics in an electrochemical sensor set up to provide an efficient diagnostic method for Y. enterecolitica. The optimum assay conditions were initially determined and the developed immunosensor was subsequently used for the detection of the bacterium in milk and human serum. The GQD-immunosensor enabled the quantification of Y. enterocolitica in a wide concentration range with a high sensitivity (LODmilk = 5 cfu mL−1 and LODserum = 30 cfu mL−1) and specificity. The developed method can be used for any pathogenic bacteria detection for clinical and food samples without pre-sample treatment. Offering a very rapid, specific and sensitive detection with a label-free system, the GQD-based immunosensor can be coupled with many electrochemical biosensors

Development of nanoparticle-modified sensor platform for cancer marker detection

The detection and quantification of cancer biomarkers in human blood is crucial to diagnose patients in the early stage of a disease. The recent advances in biosensor technology can improve detection by reducing the application time and cost without an invasive approach. The development of such detection system is a major thrust of the rapidly growing biotechnology industry. It involves a multidisciplinary research effort including chemical engineering, microelectronics and biology. This study focused on the development of nanomaterial-modified sensing platform to enhance the sensitivity for cancer marker detection. An electrochemical-based capacitive biosensor was aimed to develop using two alternative nanomaterial modification including gold nanoparticles (Au-NPs) and magnetic beads (MBs) in cancer detection for the first time. Surface Plasmon resonanse (SPR) and quartz crystal microbalance (QCM)-based sensors were initially employed to verify the bioassays and the surface chemistries. The successful achievement of these research works was transferred into an electrochemical based-capacitive biosensor to increase the sensitivity and reliability of the assays for the quantification of the biological markers. The optimized sensor methods were conducted in the capacitive sensor using standard methodologies and the detection limit was increased 6 fold without a signal amplification tool. However, the quantification of some biomarkers is difficult since they have trace threshold level in human blood and/or small size. Moreover, real patient samples include various biological molecules beside the target analyte and this makes the detection difficult due to the non-specific responses and requires the signal amplification. Due to these reasons, a novel nanoparticle modified capacitive sensor was developed and used for synchronous multiple marker detection for the first time. The developed sensor increased the sensitivity up to 600 fold (5 pg.mL-1) when compared with standard sensor assays. The results have provided alternative and effective quantification approaches to the current tools; and also a promising future for precise detection of the cancer types using multiple marker assays. The developed and improved methodologies/sensors in this thesis can also be applied for the other diseases that have biomarkers in human body

Ultrasound-Assisted Alcoholic Extraction of Lesser Mealworm Larvae Oil: Process Optimization, Physicochemical Characteristics, and Energy Consumption

The ultrasound-assisted extraction (UAE) of oil from lesser mealworm (Alphitobius diaperinus L.) larvae powders (LMLPs) using ethanol/isopropanol as the superior solvent was optimized. The evaluation of time (9.89–35.11 min), solvent-to-LMLPs (2.39–27.61 v/w), and temperature (16.36–83.64 °C) showed that the highest extraction efficiency (EE, 88.08%) and in vitro antioxidant activity (IVAA) of reducing power (0.651), and DPPH free-radical scavenging capacity (70.79%) were achieved at 22.5 v/w solvent-to-LMLPs and 70 °C for 22.64 min. Optimal ultrasound conditions significantly improved the EE than n-hexane extraction (60.09%) by reducing the electric energy consumption by ~18.5 times from 0.637 to 0.035 kWh/g. The oil diffusivity in ethanol-isopropanol during the UAE (0.97 × 10−9 m2/s) was much better than that of n-hexane (5.07 × 10−11 m2/s). The microstructural images confirmed the high efficiency of ethanol-isopropanol in the presence of ultrasounds to remove oil flakes from the internal and external surfaces of LMLPs. The improved IVAA was significantly associated with the total phenolic (4.306 mg GAE/g, r = 0.991) and carotenoid (0.778 mg/g, r = 0.937) contents (p < 0.01). Although there was no significant difference in the fatty acid profile between the two extracted oils, ethanol-isopropanol under sonication acceptably improved oxidative stability with lower peroxides, conjugated dienes and trienes, and free fatty acids

Transglutaminase-Induced Free-Fat Yogurt Gels Supplemented with Tarragon Essential Oil-Loaded Nanoemulsions: Development, Optimization, Characterization, Bioactivity, and Storability

There is a high demand for designing healthy-functional dairy gels with a newly structured protein network in the food industry. Non-fat yogurt gels enriched with stable tarragon essential oil-nanoemulsions (TEO-NEs) using crosslinking of microbial transglutaminase (MTGase) were developed. The gas chromatography-mass spectrometry analysis showed that methyl chavicol (85.66%) was the major component in TEO extracted by the hydrodistillation process. The storage-dependent droplet size and physicochemical stability data of samples at room temperature for 30 days revealed that the TEO-NE containing 0.5% tween-80 and 1:2 TEO/sunflower oil had the lowest peroxide value and droplet growth ratio. The response surface methodology-based formulation optimization of free-fat yogurt gels using MTGase (0.15–0.85 U/g) and the best TEO-NE (0.5–3.02%) using the fitted second-order polynomial models proved that the combination of 0.87% TEO-NE and 0.70 U/g MTGase led to the desired pH (4.569) and acidity (88.3% lactic acid), minimum syneresis (27.03 mL/100 g), and maximum viscosity (6.93 Pa s) and firmness (0.207 N) responses. Scanning electron microscopy images visualized that the MTGase-induced crosslinks improved the gel structure to increase the firmness and viscosity with a reduction in the syneresis rate. The optimal yogurt gel as a nutritious diet not only provided the highest organoleptic scores but also maintained its storage-related quality with the lowest mold/yeast growth and free-radical oxidation change

Synthesis of Molecularly Imprinted Polymer Nanoparticles for SARS-CoV-2 Virus Detection Using Surface Plasmon Resonance

COVID-19 caused by a SARS-CoV-2 infection was first reported from Wuhan, China, and later recognized as a pandemic on March 11, 2020, by the World Health Organization (WHO). Gold standard nucleic acid and molecular-based testing have largely satisfied the requirements of early diagnosis and management of this infectious disease; however, these techniques are expensive and not readily available for point-of-care (POC) applications. The COVID-19 pandemic of the 21st century has emphasized that medicine is in dire need of advanced, rapid, and cheap diagnostic tools. Herein, we report on molecularly imprinted polymer nanoparticles (MIP-NPs/nanoMIPs) as plastic antibodies for the specific detection of SARS-CoV-2 by employing a surface plasmon resonance (SPR) sensor. High-affinity MIP-NPs directed against SARS-CoV-2 were manufactured using a solid-phase imprinting method. The MIP-NPs were then characterized using dynamic light scattering (DLS) and atomic force microscopy (AFM) prior to their incorporation into a label-free portable SPR device. Detection of SARS-CoV-2 was studied within a range of 104–106 PFU mL−1. The MIP-NPs demonstrated good binding affinity (KD = 0.12 pM) and selectivity toward SARS-CoV-2. The AFM, cyclic voltammetry, and square-wave voltammetry studies revealed the successful stepwise preparation of the sensor. A cross-reactivity test confirmed the specificity of the sensor. For the first time, this study demonstrates the potential of molecular imprinting technology in conjunction with miniaturized SPR devices for the detection of SARS-CoV-2 particles with high-affinity and specificity. Such sensors could help monitor and manage the risks related to virus contamination and infections also beyond the current pandemic