Development of biosensors for detection of fibrinogen: a review.

Fibrinogen as a major inflammation marker and blood coagulation factor has a direct impact on the health of humanity. The variations in fibrinogen content lead to risky conditions such as bleeding and cardiovascular diseases. So, accurate methods for monitoring of this glycoprotein are of high importance. The conventional methods, such as the Clauss method, are time consuming and require highly specialized expert analysts. The development of fast, simple, easy to use, and inexpensive methods is highly desired. In this way, biosensors have gained outstanding attention since they offer means for performing analyses at the points-of-care using self-testing devices, which can be applied outside of clinical laboratories or hospital. This review indicates that different electrochemical and optical sensors have been successfully implemented for the detection of fibrinogen under normal levels of fibrinogen in plasma. The biosensors for the detection of fibrinogen have been designed based on the quartz crystal microbalance, field-effect transistor, electrochemical impedance spectroscopy, amperometry, surface plasmon resonance, localized surface plasmon resonance, and colorimetric techniques. Also, this review demonstrates the utility of the application of nanoparticles in different detection techniques.

Designing a label-free electrochemical aptasensor based on polypyrrole-l-cysteine-reduced graphene oxide nanocomposite for detection of 25-hydroxyvitamin D3.

Reliable and precise quantification of 25-hydroxyvitamin D3 in clinical samples is vital because vitamin D3 deficiency lead to several disorders, such as mental illness, osteoporosis, and coronavirus disease. Herein, we report the fabrication of a novel electrochemical aptasensor using a nanocomposite, including reduced graphene oxide, pyrrole, and l-cysteine, for the sensitive detection of 25-hydroxyvitamin D3 . Subsequently, the aptamer of 25-hydroxyvitamin D3 was immobilized on the surface of the modified electrode. Differential pulse voltammetry signals were utilized for studying the binding and measurement of 25-hydroxyvitamin D3 based on the oxidation peak. Under the optimum conditions, the designed electrochemical aptasensor exhibited a linear detection range of 0.001-150 nM, with a limit of detection of 0.006 nM. Furthermore, the proposed aptasensor selectively detected 25-hydroxyvitamin D3 compared to other analogs. Moreover, this aptasensor was successfully applied for the detection of 25-hydroxyvitamin D3 in human serum samples, which were quantified by the enzyme-linked immunosorbent assay method. The acceptable recoveries of 82.67%-111.07% demonstrated that this proposed electrochemical aptasensor can be a promising alternative for clinical methods of vitamin D determination.

A new molecularly imprinted polymer electrochemical sensor based on CuCo2 O4 /N-doped CNTs/P-doped GO nanocomposite for detection of 25-hydroxyvitamin D3 in serum samples.

25-Hydroxyvitamin D3 as a main circulating metabolite of vitamin D is usually measured in serum to evaluate the vitamin D status of humans. So, developing an accessible, fast response, sensitive, and selective detection method for 25-hydroxyvitamin D3 is highly important. In this study, we designed a sensitive and selective electrochemical sensor based on the modification of glassy carbon electrode by nanocomposite of CuCo2 O4 /nitrogen-doped carbon nanotubes and phosphorus-doped graphene oxide. Then 25-hydroxyvitamin D3 -imprinted polypyrrole was coated on the electrode surface through electropolymerization. Moreover, ferricyanide was used as a mediator for the creation of a readable signal, which was considerably decreased after rebinding of 25-hydroxyvitamin D3 on the electrode. The proposed sensor successfully detected 25-hydroxyvitamin D3 in the range of 0.002-10 µM, with a detection limit of 0.38 nM, which was highly lower than deficiency concentration (20 ng/ml; 49.92 nM). Finally, the proposed sensor was checked for detection of 25-hydroxyvitamin D3 in serum samples with recovery in the range of 80%-106.42%. The results demonstrated the applicability of the designed sensor for the detection of 25-hydroxyvitamin D3 in biological samples.

Ellagic acid as a potent anticancer drug: A comprehensive review on in vitro, in vivo, in silico, and drug delivery studies.

Ellagic acid as a polyphenol or micronutrient, which can be naturally found in different vegetables and fruits, has gained considerable attention for cancer therapy due to considerable biological activities and different molecular targets. Ellagic acid with low hydrolysis and lipophilic and hydrophobic nature is not able to be absorbed in circulation. So, accumulation inside the intestinal epithelial cells or metabolization to other urolithins leads to the limitation of direct evaluation of EA effects in clinical studies. This review focuses on the studies which supported anticancer activity of pure or fruit-extracted ellagic acid through in vitro, in vivo, in silico, and drug delivery methods. The results demonstrate ellagic acid modulates the expression of various genes incorporated in the cancer-related process of apoptosis and proliferation, inflammation related-gens, and oxidative-related genes. Moreover, the ellagic acid formulation in carriers composed of lipid, silica, chitosan, iron- bovine serum albumin nanoparticles obviously enhanced the stable release and confident delivery with minimum loss. Also, in silico analysis proved that ellagic acid was able to be placed at a position of cocrystal ADP, in the deep cavity of the protein target, and tightly interact with binding pocket residues leading to suppression of substrate availability of protein and its activation inhibition.

Biosensors based on aptamer-conjugated gold nanoparticles: A review.

Simply synthetized gold nanoparticles have been highly used in medicine and biotechnology as a result of their biocompatibility, conductivity, and being easily functionalized with biomolecules such as aptamer. Aptamer-conjugated gold nanoparticle structures synergically possess characteristics of both aptamer and gold nanoparticles including high binding affinity, high biocompatibility, enhanced target selectivity, and long circulatory half-life. Aptamer-conjugated gold nanoparticles have extensively gained considerable attention for designing of biosensing systems due to their interesting optical and electrochemical features. Moreover, biosensors based on aptamer-gold nanoparticles are easy to use, with fast response, and inexpensive which make them ideal in individualized medicine, disease markers detection, food safety, and so forth. Moreover, due to high selectivity and biocompatibility of aptamer-gold nanoparticles, these biosensing platforms are ideal tools for targeted drug delivery systems. The application of this nanostructure as diagnostic and therapeutic tool has been developed for detection of cancer in the early stage by detecting cancer biomarkers, pathogens, proteins, toxins, antibiotics, adenosine triphosphate, and other small molecules. This review obviously demonstrates that this nanostructure effectively is applicable in the field of biomedicine and possesses potential of commercialization aims.

Development of detection methods for the diagnosis and analysis of highly toxic metal phosphides: A comprehensive and critical review.

Metal phosphides, especially aluminum phosphide, and phosphine (PH3 ) are widely used as insecticides and rodenticides for protection of grains during process of storage and transportation. The main reason of poisoning with this compound is related to the conscious ingestion of salts or accidental inhalation of PH3 . So the early and accurate diagnosis of poisoning can significantly help to the effective clinical treatment or recognition of death cause. PH3 is somewhat unstable due to reaction with oxygen or hemoglobin leading to formation of oxy-acids phosphorous. Here, we critically reviewed the literature introducing the quantitative and qualitative methods for the detection of metal phosphides, PH3 , and its products. This study obviously demonstrates that during past years, different diagnosis methods have been remarkably progressed. Head-space gas chromatography and confirmatory colorimetric methods have been as the most popular techniques. Also, the gas sensors are a promising method that must be more progressed.

Biosensors, microfluidics systems and lateral flow assays for circulating microRNA detection: A review.

MicroRNAs (miRNAs) are short RNA sequences found in eukaryotic cells and they are involved in several diseases pathogenesis including different types of cancers, metabolic and cardiovascular disorders. Thus, miRNAs circulating in serum, plasma, and other body fluids are employed as biomarkers for diagnostic and prognostic purposes and in assessment of drug response. Thus, various methods have been developed for detection of miRNAs including northern blotting, reverse transcriptase polymerase chain reaction (RT-PCR), next-generation sequencing, microarray, and isothermal amplification that are recognized as traditional methods. Considering the importance of early diagnosis and treatment of miRNAs-related diseases, development of simple, one-step, sensitive methods is of great interest. Nowadays developing technologies including lateral flow assay, biosensors (optical and electrochemical) and microfluidic systems which are simple fast responding, user-friendly, and are enabled with visible detection have gained considerable attention. This review briefly discusses miRNAs detection' methods, with a particular focus on lateral flow assay, biosensors, and microfluidic systems as novel and practical procedures.

A review of biosensors for the detection of B-type natriuretic peptide as an important cardiovascular biomarker.

Heart disease, as the most serious threat to human health globally, is responsible for rising mortality rates, largely due to lifestyle and diet. Unfortunately, the main problem for patients at high risk of heart disease is the validation of prognostic tests. To this end, the detection of cardiovascular biomarkers has been employed to obtain pathological and physiological information in order to improve prognosis and early-stage diagnosis of chronic heart failure. Short-term changes in B-type natriuretic peptide are known as a standard and important biomarker for diagnosis of heart failure. The most important problem for detection is low concentration and short half-life in the blood. The normal concentration of BNP in blood is less than 7 nM (25 pg/mL), which increases significantly to more than 80 pg/mL. Therefore, the development of new biosensors with better sensitivity, detection limit, and dynamic range than current commercial kits is urgently needed. This review classifies the biosensors designed for detection of BNP into electrochemical, optical, microfluidic, and lateral-flow immunoassay techniques. The review clearly demonstrates that a variety of immunoassay, aptasensor, enzymatic and catalytic nanomaterials, and fluorophores have been successfully employed for detection of BNP at low attomolar ranges. Dtection of B-type natriuretic peptide with biosensors.

Preparation, evaluation, and application of dummy molecularly imprinted polymer for analysis of hesperidin in lime juice.

Lime juice as the most commonly used natural source production can be characterized using determination of flavonoids contents such as hesperidin. So, development of analyzing methods for checking the quality and healthiness of lime juices is necessary. In this study, we aimed to set up a selective solid phase extraction method using dummy molecularly imprinting approach for extraction and separation of hesperidin in lime juice to check the quality of commercial lime juice products of Mashhad city market. The imprinted polymers were synthesized by hesperitin as dummy template due to the hesperitin solubility in the wide range of porogenic solvents. The specificity extent of synthesized polymers toward hesperidin was tested and optimum one was used as adsorbent in solid-phase extraction cartridge. The dummy molecularly imprinted polymer with high adsorption capacity for hesperidin (dissociation constant 0.12 µM) was successfully used for extraction and clean-up of hesperidin in the lime juice matrix prior to analysis by high-performance liquid chromatography. The analysis of hesperidin was done in the range of 0.312-50 µg/mL with detection limit of 0.05 µg/mL. This technique was successfully set up to remove the interfering compounds for analysis of hesperidin in commercial lime juice products.

Beneficial effects of celery (Apium graveolens) on metabolic syndrome: A review of the existing evidences.

The metabolic syndrome (MetS) is a cluster of multiple conditions that includes hypertension, dyslipidemia, abdominal obesity, and hyperglycemia disorders. Most studies revealed that the MetS is accompanied with an increased risk for cardiovascular disease, Type 2 diabetes mellitus, and insulin resistance. It can be said that, in treating or preventing the MetS and its components, lifestyle adjustment and weight loss have a vital role. According to various studies, among natural compounds, celery (Apium graveolens) is one of the most important sources of phytochemicals such as phenolic acids, flavones, flavonols, and antioxidants such as vitamin C, beta-carotene (Provitamin A), and manganese. These antioxidants have a role in decreasing the oxidative damage. The phytochemicals in celery decrease the activity of proinflammatory cytokines and prevent inflammation. Also, flavonoids in celery suppress cardiovascular inflammation. Oxidative stress and inflammation in the blood stream are the main risk factors in increasing cardiovascular disease, especially atherosclerosis. Celery phthalides leads to expanding of smooth muscle in the blood vessels and lower blood pressure. As a result, the most active ingredients in celery (A. graveolens (have shown hypolipidemic, antidiabetic, and hypotensive properties. In this review, we summarized the mechanisms underlying the protective effects of celery components on insulin action, glucose, lipid metabolism, and blood pressure.

Magnetized silane-coupling agent KH-570 based solid-phase extraction followed by gas chromatography-flame ionization detection to determine venlafaxine in human hair and aqueous environmental samples.

In the present study, a novel adsorbent, Fe3O4 magnetic nanoparticles (MNPs) functionalized by silane-coupling agent KH-570, was successfully synthesized. The prepared MNPs were characterized by Fourier-transform infrared spectroscopy and transmission electron microscopy. It was applied as functionalized magnetic nano-adsorbent for magnetic solid-phase extraction of trace levels of venlafaxine using gas chromatography with flame ionization detector. This method was developed and optimized for use in analysis of venlafaxine in human hair and aqueous environmental samples. The main factors influencing the extraction efficiency including pH of sample, amount of the MNPs, adsorption time, volume of sample, and desorption conditions such as volume of solvent and desorption time were studied and optimized. Under the optimized experimental conditions, good linearity was observed in the range of 1-1,000 µg L(-1) for aqueous environmental samples with correlation coefficients (R (2)) 0.996. The limits of detection and quantification were 0.1 and 0.5 µg L(-1), respectively. Good reproducibility with the relative standard deviations (n = 5) 3.21 % was obtained. The developed method was successfully applied to the extraction of venlafaxine from spiked human hair, river water, and surface water samples and the relative recoveries of 89.36, 93.43, and 94.99 % were obtained, respectively. The results indicated that Fe3O4/KH-570 MNPs have a satisfying extraction efficiency and can be served as a sensitive, inexpensive, and reliable method for analysis of antidepressant drugs such as venlafaxine in biological and aqueous environmental samples.

Aptamer-Based Targeting of Cancer: A Powerful Tool for Diagnostic and Therapeutic Aims.

Cancer is known as one of the most significant causes of death worldwide, and, in spite of novel therapeutic methods, continues to cause a considerable number of deaths. Targeted molecular diagnosis and therapy using aptamers with high affinity have become popular techniques for pathological angiogenesis and cancer therapy scientists. In this paper, several aptamer-based diagnostic and therapeutic techniques such as aptamer-nanomaterial conjugation, aptamer-drug conjugation (physically or covalently), and biosensors, which have been successfully designed for biomarkers, were critically reviewed. The results demonstrated that aptamers can potentially be incorporated with targeted delivery systems and biosensors for the detection of biomarkers expressed by cancer cells. Aptamer-based therapeutic and diagnostic methods, representing the main field of medical sciences, possess high potential for use in cancer therapy, pathological angiogenesis, and improvement of community health. The clinical use of aptamers is limited due to target impurities, inaccuracy in the systematic evolution of ligands via exponential enrichment (SELEX)stage process, and in vitro synthesis, making them unreliable and leading to lower selectivity for in vivo targets. Moreover, size, behavior, probable toxicity, low distribution, and the unpredictable behavior of nanomaterials in in vivo media make their usage in clinical assays critical. This review is helpful for the implementation of aptamer-based therapies which are effective and applicable for clinical use and the design of future studies.

Application of green-synthesized carbon dots for imaging of cancerous cell lines and detection of anthraquinone drugs using silica-coated CdTe quantum dots-based ratiometric fluorescence sensor.

Chemotherapy drugs of daunorubicin and doxorubicin treat cancers with many side effects. So, detection of them in the biological system for regulation and controlling of usage is essential. In this study, a ratiometric fluorescent method was introduced for detection of daunorubicin and doxorubicin using bell pepper-based carbon dots, as the variable signal, and silica-coated CdTe quantum dots, as the constant signal. The detection was done based on variations of carbon dots intensity in the presence of drugs in comparison with the constant intensity of silica-coated CdTe quantum dots. The proposed ratiometric fluorescent method was successfully used for detection of daunorubicin and doxorubicin range of 54.37-13594.34 nmolL-1 and 86.2-17242 nmolL-1, with a detection limit of 18.53 nmolL-1 and 29 nmolL-1, respectively. Also, this method was used for detection of drugs in serum samples with recovery ranges of 86.14-99.62 (RSD 3-1.47%) and 86.32-97.53 (3.38-1.48%), respectively. Finally, after evaluation of carbon dots toxicity by MTT test, carbon dots was applied for imaging of prostate cancer cell lines (PC-3) and breast cancer cell lines (MCF7). The results demonstrated that despite improvement of the repeatability and interferences reduction by ratiometric method, also carbon dots were successfully applied for imaging of cell lines.

A Critical Systematic Review of Developing Aptasensors for Diagnosis and Detection of Diabetes Biomarkers.

Diabetes mellitus is known as an epidemic problem of public health in worldwide. According to the reports of International Diabetes Federation, the global number of diabetic adults has been growing annually. Unfortunately, millions of diabetes cases may remain undiagnosed every year. Unfortunately, the glucose level of blood can be fluctuated by lifestyle. So, development of reliable, simple and fast response diagnostic methods is urgently required. Aptamer-based sensors have been recently developed as a sensitive and fast method for the diagnosis and detection of diabetes. We systematically checked the scientific literature including studies related to aptasensors as a diagnostic tool for diabetes. Many electronic databases such as Google Scholar, Scopus, PubMed and Science Direct were searched up to 2020. The present study obviously demonstrates important and unavoidable role of aptasensors as a potential technique for the diagnosis of diabetes. Different aptasenosrs such as optical, mass-related, microfluidic, and electrochemical aptasenors were successfully designed for diagnosis of diabetic biomarkers in desired range which is necessary for diagnosis or pre-diagnosis of diabetes. Although the introduced aptasensors were interestingly useful for detection of biomarkers in biological samples, but some defects may limit the incorporation of aptasensors, especially optical, mass-related, and microfluidic types, and lateral flow strips with point-of-care test (POCT) method which is necessary for self-controlling the diabetes. The results obviously demonstrate that electrochemical aptasensors, specially label-free types, due to the unbelievable sensitivity and easy to fabrication can be a promising methods for designing the POCT chips to diagnosis the diabetic biomarkers.

Application of a transition metal oxide/carbon-based nanocomposite for designing a molecularly imprinted poly (l-cysteine) electrochemical sensor for curcumin.

In this study an electrochemical sensor was fabricated for detection of curcumin, as a functional herbal food, using molecularly imprinted polymer and highly conductive transition metal oxide/carbon-based nanocomposite. In this way, CuCo2O4/nitrogen-doped carbon nanotubes/phosphorus-doped graphene oxide nanocomposite was dropped on the electrode. This nanocomposite synergically possesses conductivity features of copper and phosphorus-doping sites, specific surface area of carbon nanotubes, and carbons Fermi level of graphene oxide. In the following, l-Cystein electropolymerized on the electrode in presence of curcumin. The sensor was produced by removing curcumin from poly (L- cystein) matrix. The sensor was successfully used for detection of curcumin in the ranges of 0.1-1 µmol L-1 and 1-30 µmol L-1, with acceptable detection limit (30 nmol L-1). Finally, the proposed method was used for detection of curcumin in serum samples with recoveries of 80-110.87%. The results demonstrated that aforementioned method can be used for detection of curcumin in biological samples.

Development of Lateral Flow Assays for Rapid Detection of Troponin I: A Review.

Troponin I as a particular and major biomarker of cardiac failure is released to blood demonstrating hurt of myocardial cells. Unfortunately, troponin I detection in the first hours of acute myocardial infarction usually faces with most negligence. Therefore, developments of point of care devices such as lateral flow strips are highly required for timely diagnosis and prognosis. Lateral flow assays are low-cost paper-based detection platforms relying on specific diagnostic agents such as aptamers and antibodies for a rapid, selective, quantitative and semi-quantitative detection of the analyte in a complex mixture. Moreover, lateral flow assay devices are portable, and their simplicity of use eliminates the need for experts or any complicated equipment to operate and interpret the test results. Additionally, by coupling the lateral flow assay technology with nanotechnology, for labeling and signal amplification, many breakthroughs in the field of diagnostics have been achieved. The present study reviews the use of lateral flow assays in early stage, quantitative, and sensitive detection of cardiac troponin I and mainly focuses on the structure of each type of developed lateral flow assays. Finally, this review summarized the improvements, detection time, and limit of detection of each study as well as the advantages and disadvantages.

Selective isolation of sesquiterpene coumarins from asafoetida using dummy molecularly imprinted solid phase extraction method.

Due to the biological features of sesquiterpene coumarins and incomparable interest in therapeutics application of natural products, extraction of sesquiterpene coumarins from asafoetida have gained highly attention. One of the most important problems is removal of sulfur containing compounds which are co-existed with sesquiterpene coumarins. So employment of new methods for selective extraction and cleanup of sesquiterpene coumarins is very substantial. In this study using dummy molecularly imprinting technique, 7-hydroxycoumarin-imprited polymer was synthesized and after evaluation of binding properties of polymers, the optimum one was used as sorbent in solid phase extraction. Afterwards dummy molecularly imprinting solid phase extraction (DMISPE) method was calibrated for simultaneous extraction of galbanic acid, 7-isopentenyloxy coumarin and auraptene from aqueous media before high performance liquid chromatography with UV detector (HPLC-UV) analysis. The recovery was in the range of 68.32%-84.69%, which were in the acceptable range compared to previous works. Finally, the calibrated DMISPE method was used for extraction and cleanup of sesquiterpene coumarins from asafetida plant. The concentration of isosamarcandin, kellerin and farnesiferol in asafoetida extract was obtained 0.8, 2.7, and 5 µg/mL, respectively, using standard addition method.

Preparation, evaluation and application of core-shell molecularly imprinted particles as the sorbent in solid-phase extraction and analysis of lincomycin residue in pasteurized milk.

In this study, core-shell lincomycin-imprinted polymers were successfully synthesized and their binding properties evaluated. The functional monomers of methacrylamide and acrylamide were used for synthesis of core and shell, respectively. The optimum synthesized core-shell molecularly imprinted polymer (MIP) was applied as a sorbet in solid phase extraction cartridge. Afterwards, the method of core-shell molecularly imprinted solid phase extraction (CSMISPE) was used for pre-concentration and clean-up of lincomycin in the milk matrix prior to analysis via high performance liquid chromatography equipped with UV detector (HPLC-UV). The linear range for analysis of lincomycin in the milk matrix using introduced method was obtained from 0.08 to 2 µg/mL with recovery range of 80%-89%. The limit of detection and limit of quantification were 0.02 µg/mL and 0.08 µg/mL, respectively. Finally, calibrated CSMISPE-HPLC-UV method was used for lincomycin residue checking and quantification in the pasteurized milk samples of Mashhad city market.

Targeted imaging of breast cancer cells using two different kinds of aptamers -functionalized nanoparticles.

Breast cancer which is the most commonly diagnosed cancer among women; have been known as a serious threat for health and life around the world. So development of an approach for early-stage diagnosis of breast cancer is vital. In this study, we designed a double aptamer-nanoparticle conjugates-based (DANP) complex for specific detection and visualization of MCF-7 cells using Mucin 1 (MUC 1) aptamer-conjugated gold nanoparticles (MUC1 apt - GNPs) and adenosine triphosphate (ATP) aptamer-conjugated CdTe quantum dots (ATP apt-QDs). The ATP apt-QDs was attached onto MUC1 apt - GNPs surface through Van der Waals forces and electrostatic interactions between ATP aptamer and GNPs leading to the formation of DANP complex. Atomic force microscopy asserted DANP complex formation. The imaging process was based on the recognition of MUC1 protein on the surface of MCF-7 cells by MUC1 aptamer and specific internalization of DANP complex into target cells (MCF-7). Existence of abundant amounts of ATP in lysosome led to release of ATP apt-QDs from the MUC1 apt-GNPs surface resulting in strong fluorescence emission. The flow cytometry analysis and fluorescence microscopy confirmed significant internalization of DANP complex into MCF-7 cells (target) in comparison with CHO cells (non-target). Based on the obtained results, the DANP complex possesses high potency for efficient detection and monitoring of breast cancer cells (MCF-7).

Simple and selective analysis of different antibiotics in milk using molecularly imprinted polymers: a review.

The frequent, sometimes illegal, use of antibiotics for therapeutic and prophylactic purposes in dairy cattle management may cause residues in milk. Because of problems concerning bacterial resistance or allergies in consumers, monitoring of residues is required. In spite of the huge development of analytical instrumentation during recent years, sample preparation is still a bottleneck of the analytical process. In this regard, efforts have been directed towards improving selectivity during extraction and clean-up of samples. Compared to traditional sorbents, molecularly imprinted polymers (MIPs) are excellent materials to provide selectivity for sample pretreatment. This review presents the application of MIPs as effective sorbents for separation, clean-up, pre-concentration and analysis of different antibiotics in milk.