Nanobiosensor Systems Research Articles

Development of nanobiosensor for therapeutic drug monitoring in personalized cancer treatment approach

Docetaxel is one of the most effective and safe chemotherapy drugs according to the World Health Organization, but its clinical use has been discontinued due to its various side effects. To reduce these side effects, the amount of docetaxel drug should be kept at the most effective level, it should be monitored in body fluids. Due to the limitations of traditional analytical methods used for this purpose, such as expensive and low sensitivity, labor-intensive and time-consuming complex preliminary preparation, efficient methods are required for the determination of the docetaxel level in the body. The increasing demand for the development of personalized therapy has recently spurred significant research into biosensors for the detection of drugs and other chemical compounds. In this study, an electrochemical-based portable nanobiosensor system was developed for the rapid, low-cost, and sensitive determination of docetaxel. In this context, mg-p(HEMA)-IMEO nanoparticles to be used as nanobiosensor bioactive layer was synthesized, characterized, and docetaxel determination conditions were optimized. According to the results obtained, the developed nanobiosensor system can detect docetaxel with a sensitivity of 2.22 mg/mL in a wide calibration range of 0.25-10 mg/mL, in only 15 min, in mixed media such as commercially available artificial blood serum and urine. determined. We concluded that the developed nanobiosensor system can be successfully used in routine drug monitoring as a low-cost biomedical device capable of direct, rapid, and specific drug determination within the scope of personalized treatment, providing point-of-care testing.

A novel electrochemical biosensor based on palladium nanoparticles decorated on reduced graphene oxide-polyaminophenol matrix for the detection and discrimination of mitomycin C-DNA and acyclovir-DNA interaction

Both the design of molecules that will interact specifically with DNA and the determination of the mechanism of action of this drug on DNA are important as they allow the control of gene expression. In particular, rapid and precise analysis of this type of interaction is a vital element for pharmaceutical studies. In the present study, a novel reduced graphene oxide/ palladium nanoparticles/ poly(2-amino-4-chlorophenol) (rGO/Pd@PACP) nanocomposite was synthesized by chemical process to modify pencil graphite electrode (PGE) surface. Here, the performance of the newly developed nanomaterial-based biosensor for drug-DNA interaction analysis has been demonstrated. For this purpose, it was determined whether this system, which was developed by selecting a drug molecule (Mitomycin C; MC) known to interact with DNA and a drug molecule (Acyclovir; ACY) that does not interact with DNA, performs a reliable/accurate analysis. Here, ACY was used as a negative control. Compared to bare PGE, the rGO/Pd@PACP nanomaterial modified sensor exhibited 17 times higher sensitivity performance in terms of guanine oxidation signal measured by differential pulse voltammetry (DPV). Moreover, the developed nanobiosensor system provided a highly specific determination between the anticancer drug MC and ACY by discrimination the interactions of these drugs with double-stranded DNA (dsDNA). ACY was also preferred in studies for the optimization of the new nanobiosensor developed. ACY was detected in a concentration as low as 0.0513 μM (51.3 nM) (LOD), and limit of quantification (LOQ) was 0.1711 μM with a linear range from 0.1 to 0.5 μM.

Development and Application of an SPR Nanobiosensor Based on AuNPs for the Detection of SARS-CoV-2 on Food Surfaces

A new transmission route of SARS-CoV-2 through food was recently considered by the World Health Organization (WHO), and, given the pandemic scenario, the search for fast, sensitive, and low-cost methods is necessary. Biosensors have become a viable alternative for large-scale testing because they overcome the limitations of standard techniques. Herein, we investigated the ability of gold spherical nanoparticles (AuNPs) functionalized with oligonucleotides to detect SARS-CoV-2 and demonstrated their potential to be used as plasmonic nanobiosensors. The loop-mediated isothermal amplification (LAMP) technique was used to amplify the viral genetic material from the raw virus-containing solution without any preparation. The detection of virus presence or absence was performed by ultraviolet-visible (UV-Vis) absorption spectroscopy, by monitoring the absorption band of the surface plasmonic resonance (SPR) of the AuNPs. The displacement of the peak by 525 nm from the functionalized AuNPs indicated the absence of the virus (particular region of gold). On the other hand, the region ~300 nm indicated the presence of the virus when RNA bound to the functionalized AuNPs. The nanobiosensor system was designed to detect a region of the N gene in a dynamic concentration range from 0.1 to 50 × 103 ng·mL-1 with a limit of detection (LOD) of 1 ng·mL-1 (2.7 × 103 copy per µL), indicating excellent sensitivity. The nanobiosensor was applied to detect the SARS-CoV-2 virus on the surfaces of vegetables and showed 100% accuracy compared to the standard quantitative reverse transcription polymerase chain reaction (RT-qPCR) technique. Therefore, the nanobiosensor is sensitive, selective, and simple, providing a viable alternative for the rapid detection of SARS-CoV-2 in ready-to-eat vegetables.

Advanced Fabrication of miRNA-Based Electrochemical Nanobiosensor for Diagnosis of Breast Cancer

Early diagnosis is the key to easy, low cost, and effective treatment of breast cancer. Therefore, studies have been accelerated to identify breast cancer diagnostic biomarkers and diagnose cancer before it progresses. The use of miR-155 as a potential biomarker in breast cancer, which has different levels at different stages of the disease, provides a simple serological test for breast cancer prognosis/diagnosis, follow-up, and treatment. Nanopolymers containing different functional groups that are formed by thiol affinity technique were synthesized by mini emulsion polymerization method and advanced characterization studies were carried out in this study to be used as bioactive layers in the nanobiosensor system for miRNA detection. The working conditions of the electrochemical nanobiosensor in which nanopolymers are used as bioactive layers were optimized. Analytical measurement characteristics and validation studies of the nanobiosensor were determined and analysis was performed on commercial blood serum. The potential of the developed electrochemical biosensor to be used as a medical diagnostic kit was explained by comparing it with commercial miRNA kit currently used for the detection of miR-155. This novel nanobiosensor provide sensitive, reliable, and rapid detection of miR-155 and it can provide the potential for breast cancer early diagnosis, prognosis, and follow-up.

Development of GO/Co/Chitosan-Based Nano-Biosensor for Real-Time Detection of D-Glucose.

Electrochemical nano-biosensor systems are popular in the industrial field, along with evaluations of medical, agricultural, environmental and sports analysis, because they can simultaneously perform qualitative and quantitative analyses with high sensitivity. However, real-time detection using an electrochemical nano-biosensor is greatly affected by the surrounding environment with the performance of the electron transport materials. Therefore, many researchers are trying to find good factors for real-time detection. In this work, it was found that a composite composed of graphite oxide/cobalt/chitosan had strong stability and electron transfer capability and was applied to a bioelectrochemical nano-biosensor with high sensitivity and stability. As a mediator-modified electrode, the GO/Co/chitosan composite was electrically deposited onto an Au film electrode by covalent boding, while glucose oxidase as a receptor was immobilized on the end of the GO/Co/chitosan composite. It was confirmed that the electron transfer ability of the GO/Co/chitosan composite was excellent, as shown with power density analysis. In addition, the real-time detection of D-glucose could be successfully performed by the developed nano-biosensor with a high range of detected concentrations from 1.0 to 15.0 mM. Furthermore, the slope value composed of the current, per the concentration of D-glucose as a detection response, was significantly maintained even after 14 days.

FET-based nanobiosensors for the detection of smell and taste.

Various nanobiosensors composed of biomaterials and nanomaterials have been developed, due to their demonstrated advantage of showing high performance. Among various biomaterials for biological recognition elements of the nanobiosensor, sensory receptors, such as olfactory and taste receptors, are promising biomaterials for developing nanobiosensors, because of their high selectivity to target molecules. Field-effect transistors (FET) with nanomaterials such as carbon nanotube (CNT), graphene, and conducting polymer nanotube (CPNT), can be combined with the biomaterials to enhance the sensitivity of nanobiosensors. Recently, many efforts have been made to develop nanobiosensors using biomaterials, such as olfactory receptors and taste receptors for detecting various smells and tastes. This review focuses on the biomaterials and nanomaterials used in nanobiosensor systems and studies of various types of nanobiosensor platforms that utilize olfactory receptors and taste receptors which could be applied to a wide range of industrial fields, including the food and beverage industry, environmental monitoring, the biomedical field, and anti-terrorism.

Revealing Lectin-Sugar Interactions with a Single Au@Ag Nanocube.

An individual nanoparticle-based plasmonic nanotechnology was used for real-time monitoring of lectin-sugar interactions, which could be designed as novel plasmonic nanobiosensors for the detection of trace concanavalin A (ConA) with high sensitivity and selectivity. The localized surface plasmon resonance (LSPR) spectra of Au@Ag nanocubes (NCs) are linearly shifted to a long wavelength with an increasing concentration of ConA. In fact, each Au@Ag NC can act as a nanobiosensor for the quantified detection of trace ConA, which enables the miniaturization of the biosensor system to nanoscale. Furthermore, the results demonstrated the perfect biosensing ability with the dual channel of dark-field microscopy images and LSPR spectra. We expect that this nanobiosensor system can provide an alternative important method for monitoring the specific binding of lectin-sugar at a single nanoparticle surface.

Influence of Chip Materials on Charge Generation in Flowing Solution in Nanobiosensors

Nowadays, nanobiosensors are being intensively developed due to the potential possibilities of their use for early diagnosis of diseases. This interest is enhanced by the fact that, as is known, a pathological process at an early stage is characterized by the appearance of marker proteins at very low (10−15 M and lower) concentrations in blood. Highly-sensitive nanobiosensor systems (including those based on an atomic force microscope, AFM) allows one to detect proteins at such low concentrations. The influence of the charge generated in the analyte solution flowing through the biosensor injector into the measuring cell during measurements is considered to be an important factor conditioning such a high detection sensitivity. In the present study, it was demonstrated that the presence of an AFM chip (made of mica and graphite) near the nozzle of the injector supplying an analyte solution into the measuring cell of the AFM-based fishing system (AFM-based nanobiosensors) causes an increase in charge generation upon the injection of the solution. Moreover, the influence of polymer materials (which are widely used in nanobiosensors) and communications on charge generation in the flow-based section of AFM-based nanobiosensors was studied. A stimulating influence of a low (femtomolar) concentration of proteins on the charge generation in polymeric injectors of flow-based nanobiosensors was demonstrated. Besides, a stimulating influence of an external low-frequency AC electric field on the charge generation in the nanobiosensor injector was found. Measurements were carried out in the temperature range corresponding to the physiological temperature (35 °C).

Fluorescent Nanobiosensors for Sensing Glucose

Glucose sensing in diabetes diagnosis and therapy is of great importance due to the prevalence of diabetes in the world. Furthermore, glucose sensing is also critical in the food and drug industries. Sensing glucose has been accomplished through various strategies, such as electrochemical or optical methods. Novel transducers made with nanomaterials that integrate fluorescent techniques have allowed for the development of advanced glucose sensors with superior sensitivity and convenience. In this review, glucose sensing by fluorescent nanobiosensor systems is discussed. Firstly, typical fluorescence emitting/interacting nanomaterials utilized in various glucose assays are discussed. Secondly, strategies for integrating fluorescent nanomaterials and biological sensing elements are reviewed and discussed. In summary, this review highlights the applicability of fluorescent nanomaterials, which makes them ideal for glucose sensing. Insight on the future direction of fluorescent nanobiosensor systems is also provided.

Notch signaling in regulating angiogenesis in a 3D biomimetic environment.

Angiogenesis is a complex cellular process involving highly orchestrated invasion and organization of endothelial cells (ECs) in a three-dimensional (3D) environment. Recent evidence indicates that Notch signaling is critically involved in regulating specialized functions and distinct fates of ECs in newly formed vasculatures during angiogenesis. Here, we demonstrated, for the first time, the application of a microengineered biomimetic system to quantitatively investigate the role of Notch signaling in regulating early angiogenic sprouting and vasculature formation of ECs in a 3D extracellular matrix. Morphological features of angiogenesis including invasion distance, invasion area, and tip cell number were quantified and compared under pharmacological perturbations of Notch signaling. In addition, influences of Notch signaling on EC proliferation in angiogenic vasculatures and directional invasion of tip cells were also investigated. Moreover, leveraging a novel nanobiosensor system, mRNA expression of Dll4, a Notch ligand, was monitored in invading tip cells using live cell imaging during the dynamic angiogenic process. Our data showed that inhibition of Notch signaling resulted in hyper-sprouting endothelial structures, while activation of Notch signaling led to opposite effects. Our results also supported the role of Notch signaling in regulating EC proliferation and dynamic invasion of tip cells during angiogenesis.

Nano-Biosensor for Monitoring the Neural Differentiation of Stem Cells.

In tissue engineering and regenerative medicine, monitoring the status of stem cell differentiation is crucial to verify therapeutic efficacy and optimize treatment procedures. However, traditional methods, such as cell staining and sorting, are labor-intensive and may damage the cells. Therefore, the development of noninvasive methods to monitor the differentiation status in situ is highly desirable and can be of great benefit to stem cell-based therapies. Toward this end, nanotechnology has been applied to develop highly-sensitive biosensors to noninvasively monitor the neural differentiation of stem cells. Herein, this article reviews the development of noninvasive nano-biosensor systems to monitor the neural differentiation of stem cells, mainly focusing on optical (plasmonic) and eletrochemical methods. The findings in this review suggest that novel nano-biosensors capable of monitoring stem cell differentiation are a promising type of technology that can accelerate the development of stem cell therapies, including regenerative medicine.

Cytochrome P450-3A4/Copper-Poly(Propylene Imine)-Polypyrrole Star Co-Polymer Nanobiosensor System for Delavirdine - A Non-Nucleoside Reverse Transcriptase Inhibitor HIV Drug

HIV and AIDS are among the world’s pandemics that pose serious concern to almost every individual in the world. With the current level of availability of anti-retroviral (ARV) drugs and the ease of accessibility of treatment in many countries such as South Africa, the disease can be controlled by suppressing the viral load of an infected individual. These anti HIV drugs such as delavirdine are metabolised by enzymes which are found in the liver microsomes, particularly those of the cytochrome P450 family. Due to the fact that the metabolic rate of a patient determines the effect of the drug, the drug could either have a beneficial or an adverse effect once it is administered. It is therefore imperative that the metabolic profile of a patient is determined to ensure proper dosing of the ARV drugs. In this study a nanobiosensor system was devised and used for the determination of the metabolism of delavirdine (DLV), a non-nucleoside reverse transcriptase inhibitor (NNRTI) ARV drug. The nanobiosensor was prepared by the entrapment of the isoenzyme CYP3A4 into a pre-formed electro active carrier matrice consisting of a dendrimeric copper generation-2 poly(propylene imine)-co-polypyrrole star copolymer (Cu(G2PPI)-co-PPy). The metallo-dendrimer was used as a host for the enzyme and provided the necessary bio-compatible environment that allowed the direct transfer of electrons between the enzyme’s active centres and platinum electrode surface. (Cu(G2PPI)-co-PPy) was prepared by the incorporation of the copper metal into the G2PPI and the electropolymerization of pyrrole onto the Cu(G2PPI). The incorporation of Cu into G2PPI was determined by Fourier transform infrared (FTIR) spectroscopy which did not show the presence of the Cu but showed an increase in the intensities of the peaks after the incorporation. The surface morphology of Cu(G2PPI-2Py) was confirmed by the use of high resolution scanning electron microscopy (HRSEM) which showed a difference in the surface morphology of the dendrimer moiety with the addition of the copper metal. The HRSEM images after Cu incorporation resulted in the change from rough surface to smooth surface with open cavities which were essential for the entrapment of the biological systems (CYP3A4). The energy band gap of (Cu(G2PPI)-co-PPy) were determined to be 3.85 eV, signifying that the copolymer is characteristic of a biocompatible semiconductive platform for applications in biosensors. The star copolymer (Cu(G2PPI)-co-PPy) was characterized using cyclic voltammetry where it was confirmed that the material was electroactive and conducting due to electron movement along the polymer chain. A diffusion co-efficient (Do) value of 8.64 x 10-5 cm2/s was determined for the material indicating a slow electron transfer kinetics within the diffusion layer. The resultant nanobiosensor parameters include a dynamic linear range (DLR) of 0.01-0.06 nM, a limit of detection (LOD) of 0.025 nM and a sensitivity value of 0.379 μA/nM.

Nanotechnology and Its Future Prospective for Sustainable Agriculture

Nanotechnology is essentially miniaturized technology which aims to advance the goals of science. Nanotechnology is working at nanoscopic level with the smallest possible particles which raise hopes for improvement in agriculture by solving various problems which remain unsolved conventionally. Crop improvement in agriculture is a continuous process in which development of different improved varieties to suite the growing needs are done through conventional breeding and biotechnological approaches. Nanobiotechnology is essentially miniaturized biotechnology which involves nanotechnology to advance the goals of biology. Recently scientists have started using nanotechnology to deliver the genes to specific sites at cellular levels and rearrange the atoms in the DNA of the same organism to achieve expression of desired character, bypassing time consuming process of gene transformation from the foreign organisms. In the environmentally controlled condition, agriculture and precision farming input requirement of crops are detected based on needs and fulfill requirement in right time at right place with the help of nano-biosensor system. In agriculture new molecular and cellular biology tools are expected to provide food quality, disease prevention and treatment in plants e.g. disease diagnosis, screening and treatment in farming practices involving vector, pest detection and control and disease monitoring. Some of the nano particles that have entered into the arena of controlling plant diseases are nano forms of carbon, silver, silica and alumino-silicates. Diagnosis of a disease in its very early stage can play important role in treatment. Nanoherbicides are being developed to address the problems in perennial weed management and exhausting weed seed bank. The current applications in agricultural sectors are relatively few because they are still emerging. However, a number of nanotechnology-driven products and applications in agricultural sectors have been increasing steadily in recent years and are predicted to grow in future.

Chemically amplified cytochrome P450-2E1 drug metabolism nanobiosensor for rifampicin anti-tuberculosis drug

Fully susceptible tuberculosis (TB) develops secondary drug resistance during therapy due to inappropriate dosing of treatment drugs, inadequate treatment, non-adherence to the prescribed regimen or using low quality medication. Therefore, a fast and reliable method for the determination of a patient's metabolic profile for TB drugs is essential for appropriate dosing of these drugs. A nanobiosensor for the determination of the biotransformation of rifampicin (a TB drug) was developed using ethylene glycol bis(succinic acid N-hydroxysuccinimide ester) (EG)-modified cytochrome P450-2E1 (CYP2E1). The EG-CYP2EI enzyme system was electrodeposited on gold electrodes derivatised with polyvinylpyrrolidone/silver nanoparticles/poly(8-anilino-1-naphthalene sulphonic acid) (PVP-AgNPs/PANSA) nanocomposite. The electrochemical impedance spectroscopy (EIS) and transmission electron microscopy (TEM) analyses of the Au/PVP-AgNPs/PANSA/EG-CYP2E1 nanobiosensor system revealed that PVP-AgNPs/PANSA is a highly electroactive nanocomposite whose morphology and properties were suitable for the immobilisation of CYP2E1. The response profile of the nanobiosensor for rifampicin was studied by cyclic voltammetry (CV), differential voltammetry (DPV) and steady state amperometry under aerobic conditions. The dynamic linear range of the nanobiosensor (0.025 - 14μM) covers the peak rifampicin serum level value of 0.045μM.

Integrated nanobiosensor technology for biomedical application

Integrated nanobiosensor technology for biomedical application Chulhee Choi1,21Department of Bio and Brain Engineering, 2Graduate School of Medical Science and Engineering, 3KI for the BioCentury 4Optical Bioimaging Center, KAIST, Daejeon, Republic of KoreaAbstract: Advances in nanotechnology have led to the development of nanoscale biosensors that have exquisite sensitivity and versatility. The biomedical application of nanobiosensors is wide; moreover, the future impact of nanobiosensor systems for point-of-care diagnostics will be unmatched. The ultimate goal of nanobiosensors is to detect any biochemical and biophysical signal associated with a specific disease at the level of a single molecule or cell. This technology will revolutionize conventional medical practices by enabling early diagnosis of chronic debilitating diseases, ultrasensitive detection of pathogens, and long-term monitoring of patients using biocompatible integrated medical instrumentation. In the present commentary, current state-of-the art principles of nanobiosensor systems and integration into lab-on-a-chip devices are discussed along with future perspectives.Keywords: nanotechnology, biosensor, diagnostics, point-of-care, lab-on-a-chip, microfluidics

Self-indicating nanobiosensor for detection of 2,4-dinitrophenol

A colorimetric nanobiosensor was developed based on the chromogenic effect of latex microspheres hybridization with gold nanoparticles. A toxin analog, 2,4-dinitrophenol–bovine serum albumin (DNP–BSA) was attached to gold nanoparticles and was allowed to hybridize via antigen–antibody association with an anti-DNP antibody on latex microspheres, changing the color of latex microspheres pinkish-red. A model toxin, DNP–glycine (GLY), was detected and quantified via a competition that occurs between the analog-conjugated-gold nanoparticles and the toxin molecules for the binding pocket in the anti-DNP antibody. When the gold nanoparticles were displaced from host latex microspheres in the presence of toxin molecules, a visible color change occurred from pinkish-red to white. This proof-of-concept self-indicating nanobiosensor detected the model toxin rapidly, and the results were quantifiable. When further developed, this nanobiosensor system will be useful at the consumer end to help improve food safety and counter possible bioterrorism attacks.

Spectroelectrochemical Reactivities of Novel Polyaniline Nanotube Pesticide Biosensors

AbstractSummary: The preparation and characterisation of electrosynthetic polyaniline nanomaterials doped with phenanthrene sulphonic acid (PSA) is being presented. The polymeric nanomaterials prepared include processable poly(o‐methoxy aniline) (POMA) and poly(2,5‐dimethoxy aniline) (PDMA). Spectroelectrochemical reactivities of the electroactive polymeric nanotube systems as well as the nanobiosensor systems were studied by SEM, FTIR, UV‐Vis and Subtractively Normalised Fourier Transformed Infrared Spectroscopy (SNIFTIRS) techniques. Furthermore, cyclic and differential pulse voltammetric studies of the nanomaterials were also performed using platinum or thiol‐modulated gold electrodes. The SEM studies confirmed the nanorod morphology of the polyanilines. The heterogeneous rate constant, ko, for the nanopolymeric material and the diffusion coefficient of electrons, De, was calculated and found to be in agreement with values expected for electron hopping along conducting polymer chains. Organophosphate pesticide nanobiosensor devices were prepared by encapsulating acetylcholinesterase (AChE) in the nanopolymeric composite. The biosensor amperometric response to the organophosphate pesticide called diazinon and the carbamate pesticide called carbofuran were studied. The sensor responses to pesticides followed typical electrochemical Michaelis‐Menten kinetics.