Multilayered Mesoporous Composite Nanostructures for Highly Sensitive Label-Free Quantification of Cardiac Troponin-I.

Cardiac troponin-I (cTnI) is a well-known biomarker for the diagnosis and control of acute myocardial infarction in clinical practice. To improve the accuracy and reliability of cTnI electrochemical immunosensors, we propose a multilayer nanostructure consisting of Fe3O4-COOH labeled anti-cTnI monoclonal antibody (Fe3O4-COOH-Ab1) and anti-cTnI polyclonal antibody (Ab2) conjugated on Au-Ag nanoparticles (NPs) decorated on a metal-organic framework (Au-Ag@ZIF-67-Ab2). In this design, Fe3O4-COOH was used for separation of cTnI in specimens and signal amplification, hierarchical porous ZIF-67 extremely enhanced the specific surface area, and Au-Ag NPs synergically promoted the conductivity and sensitivity. They were additionally employed as an immobilization platform to enhance antibody loading. Electron microscopy images indicated that Ag-Au NPs with an average diameter of 1.9 ± 0.5 nm were uniformly decorated on plate-like ZIF-67 particles (with average size of 690 nm) without any agglomeration. Several electrochemical assays were implemented to precisely evaluate the immunosensor performance. The square wave voltammetry technique exhibited the best performance with a sensitivity of 0.98 mA mL cm-2 ng-1 and a detection limit of 0.047 pg mL-1 in the linear range of 0.04 to 8 ng mL-1.

Point-of-care cancer diagnostic devices: From academic research to clinical translation.

Early and timely diagnosis of cancer plays a decisive role in appropriate treatment and improves clinical outcomes, improving public health. Significant advances in biosensor technologies are leading to the development of point-of-care (POC) diagnostics, making the testing process faster, easier, cost-effective, and suitable for on-site measurements. Moreover, the incorporation of various nanomaterials into the sensing platforms has yielded POC testing (POCT) platforms with enhanced sensitivity, cost-effectiveness and simplified detection schemes. POC cancer diagnostic devices provide promising platforms for cancer biomarker detection as compared to conventional in vitro diagnostics, which are time-consuming and require sophisticated instrumentation, centralized laboratories, and experienced operators. Current innovative approaches in POC technologies, including biosensors, smartphone interfaces, and lab-on-a-chip (LOC) devices are expected to quickly transform the healthcare landscape. However, only a few cancer POC devices (e.g. lateral flow platforms) have been translated from research laboratories to clinical care, likely due to challenges include sampling procedures, low levels of sensitivity and specificity in clinical samples, system integration and signal readout requirements. In this review, we emphasize recent advances in POC diagnostic devices for cancer biomarker detection and discuss the critical challenges which must be surmounted to facilitate their translation into clinical settings.

Point-of-care biosensors in medicine: a brief overview of our achievements in this field based on the conducted research in EMRI (endocrinology and metabolism research Institute of Tehran University of medical sciences) over the past fourteen years.

The growing demand of diagnostic tools with enhanced analytical characteristics in term of sensitivity, selectivity, and low response time has encouraged researches to conduct their research towards development of point-of-care (POC) biosensors. POC diagnostic devices are powerful tools for detection, diagnosis, and monitoring of diseases at its initial stage. The above characteristics encouraged us to conduct active multidisciplinary and collaborative research oriented towards the design and development of POC sensing systems. Here, we present a brief overview of our recent achievement in the field of biomedical POC devices implemented in paper based microfluidic and screen printing electrodes and discuss the critical limitations that need to be surmounted to facilitate their translation into clinical practice in the future.

A review on nanomaterial-based field effect transistor technology for biomarker detection.

Field effect transistor (FET) based sensors have attractive features such as small size, ease of mass production, high versatility and comparably low costs. Over the last decade, many FET type biosensors based on various nanomaterials (e.g. silicon nanowires, graphene, and transition metal dichalcogenides) have been developed to detect various classes of biomolecular targets due to their integration into portable and rapid test systems, both for use in the clinical lab and in point-of-care testing. This review (with 197 refs.) starts with an introduction into the specific features of FET biosensor technology. This is followed by a description of the essentials of methods for immobilization of recognition elements. The next section discusses the progress that has been made in FET based biosensors using semiconducting nanostructures composed of silicon, graphene, metal oxides, and transition metal dichalcogenides. A further section is devoted to microfluidic systems combined with FET biosensors. We then emphasize the biosensing applications of these diagnostic devices for analysis of clinically relevant biomarkers, specifically to sensing of neurotransmitters, metabolites, nucleic acids, proteins, cancer and cardiac biomarkers. Two tables are presented which summarize advances in applications of 1D and 2D nanomaterial-based FETs for biomarker sensing. A concluding section summarizes the current status, addresses current challenges, and gives perspective trends for the field. Graphical abstract Field effect transistor devices based on the use of 1D and 2D semiconductor nanostructures (so called nano-FETs) are making use of materials including silicon nanowires, graphene, zinc oxide, indium oxide, titanium oxide, and molybdenum disulfide that are further modified with recognition elements for biosensing application.

Point of care testing: The impact of nanotechnology.

Point-of-care (POC) diagnostic devices are integral in the health care system and particularly for the diagnosis and monitoring of diseases. POC testing has a variety of advantages including the ability to provide rapid and accurate results, ease of use, low cost, and little need for specialized equipment. One of the goals of POC testing is the development of a chip-based, miniaturized, portable, and self-containing system that allows for the assay of different analytes in complex samples. To achieve these goals, many researchers have focused on paper-based and printed electrode technologies as the material for fabricating POC diagnostic systems. These technologies are affordable, sensitive, user-friendly, rapid, and scalable for manufacturing. Moreover, the combination such devices with nanomaterials provide a path for the development of highly sensitive and selective biosensors for future generation POC tools. This review article discusses present technologies in on-site or at home POC diagnostic assays implemented in paper-based microfluidic and screen printing devices over the past decade as well as in the near future. In addition, recent advances in the application of nanomaterials such as gold nanoparticles, carbon nanotubes (CNTs), magnetic nanoparticles, and graphene in POC devices will be reviewed. The factors that limit POC testing to become real world products and future directions are also identified.

Towards DNA methylation detection using biosensors.

DNA methylation, a stable and heritable covalent modification which mostly occurs in the context of a CpG dinucleotide, has great potential as a biomarker to detect disease, provide prognoses and predict therapeutic responses. It can be detected in a quantitative manner by many different approaches both genome-wide and at specific gene loci, in various biological fluids such as urine, plasma, and serum, which can be obtained without invasive procedures. The current, classical methods are effective in studying DNA methylation patterns, however, for the most part; they have major drawbacks such as expensive instruments, complicated and time consuming protocols as well as relatively low sensitivity, and high false positive rates. To overcome these obstacles, great efforts have been made toward the development of reliable sensor devices to solve these limitations, providing sensitive, fast and cost-effective measurements. The use of biosensors for DNA methylation biomarkers has increased in recent years, because they are portable, simple, rapid, and inexpensive which offers a straightforward way to detect methylated biomarkers. In this review, we give an overview of the conventional techniques for the detection of DNA methylation and then will focus on recent advances in biosensor based methylation detection that eliminate bisulfite conversion and PCR amplification.

Anti-inflammatory effects of eugenol nanoemulsion as a topical delivery system.

Eugenol is the main constituent of clove oil with anti-inflammatory properties. In this work, for the first time, O/W nanoemulsion of eugenol was designed for the evaluation of anti-inflammatory effects as a topical delivery system. Topical formulations containing 1%, 2% and 4% of eugenol as well as a nanoemulsion system containing 4% eugenol and 0.5% piroxicam were prepared. Further to physicochemical examinations, such as determination of particle size, polydispersity index, zeta potential and physical stability, anti-inflammatory activity was examined in carrageenan-induced paw edema in rats. The optimum formulation was found to contain 2% eugenol (oil phase), 14% Tween 20 (surfactant) and 14% isopropyl alcohol (co-surfactant) in water. Nanoemulsion with polydispersity index of 0.3 and median droplet diameter of 24.4 nm (d50) was obtained. Animal studies revealed that the nanoemulsions exhibited significantly improved anti-inflammatory activity after 1.5 h, compared with marketed piroxicam gel. Additionally, it was shown that increasing the concentration of eugenol did not show higher inhibition of inflammation. Also, the nanoemulsion having piroxicam showed less anti-inflammatory properties compared with the nanoemulsion without piroxicam.

Effects of prenatal exposure to single-wall carbon nanotubes on reproductive performance and neurodevelopment in mice.

Carbon nanotubes with extraordinary properties may become a novel drug and gene delivery tool in nanomedicine; however, insufficient information is available regarding their biosafety. Therefore, this work was performed to study the effect of prenatal exposure of single-walled carbon nanotubes (SWCNTs) on reproductive and neurobehavioral endpoints in mice. Thirty pregnant female mice were assigned to three groups (n = 10 for each group). The two treated groups were injected intraperitoneally (i.p.) with 1 or 10 mg/kg body weight (b.w.) of SWCNTs suspended in 1 ml of phosphate buffer saline (PBS) on gestational days 0 and 3. The control group was injected i.p. with an equal volume of PBS. The neurobehavioral ontogeny of pups was evaluated using a modified Fox battery. A decrease in litter size on postnatal day 2 was observed in the group treated with 10 mg/kg b.w. of SWCNTs whereas no significant differences between groups were observed in any other parameters. The behavioral development of pups did not show significant differences during growth except for the surface righting reflex, which showed significant delay compared to control in the group treated with 1 mg/kg b.w. SWCNTs. Moreover, exposed offspring (10 mg/kg b.w. SWCNTs) displayed enhanced anxiety in the elevated plus maze; however, other ethological analysis (Morris water maze and open field test) did not show behavioral changes in the experimental groups. In conclusion, the present results demonstrated small changes in offspring sensory and motor development following exposure to SWCNTs and support the idea that SWCNT risk assessment merits further investigation.

The effects of vitamin d on insulin release from isolated islets of rats.

BACKGROUND: Vitamin D (vit D) affects glucose metabolism. Receptors of vitamin D have been identified in ß cells and studies show that vitamin D deficiency reduces glucose-stimulated insulin secretion (GSIS). OBJECTIVES: The aim of this study was to examine the effect of vitamin D on insulin release from isolated islets of rats. MATERIALS AND METHODS: Islets were isolated from male Wistar rats, weighing 200-250 grams, using the collagenase digestion method. Insulin release was assessed following 24 and 48 hours coincubation of islets with vitamin D (0.1, 1 and 10 nM) and glucose (5.6, 11.1 and 16.7 mM). In addition, islets were preincubated with vitamin D for 24 and 48 hours and GSIS was assessed for one hour in the presence of 5.6 and 16.7 mM glucose. RESULTS: Coincubation of islets with vitamin D (10 nM) and 11.1 mM glucose increased islet insulin release (37.27 ± 3.75 vs. 24.64 ± 2.83 ng/islet/24 hours; P < 0.05), while vitamin D (1 and 10 nM) decreased insulin release in the presence of 16.7 mM glucose (21.14 ± 3.58 and 18.65 ± 3.84 vs. 37.71 ± 4.63 ng/ islet/24 hours; P < 0.05). Islets preincubation with vitamin D (1 and 10 nM) increased GSIS in the presence of 16.7 mM glucose (4.39 ± 0.73 and 4.39 ± 0.63 vs. 2.07 ± 0.43 ng/islet/1 hour; P < 0.05). CONCLUSIONS: Preincubation of islets with vitamin D increased GSIS but decreased insulin release in coincubation with high levels of glucose. Insulin secretion from ß cells in the presence of glucose seems to be related to the dosage of vitamin D and duration of preincubation.

Pediatric reference values for serum zinc concentration in Iranian subjects and an assessment of their dietary zinc intakes.

OBJECTIVES: To determine pediatric reference values for serum zinc concentration in Iranian subjects. DESIGN AND METHODS: Serum zinc concentration was measured by flame atomic absorption spectrometry in 699 children and adolescents. Reference values for serum zinc were determined according to the Clinical and Laboratory Standards Institute/International Federation of Clinical Chemistry guidelines. Dietary zinc intake was assessed using a validated semiquantitative food frequency questionnaire. RESULTS: Overall 95% reference values for serum zinc concentrations were 9.7-31.5, 9.2-30.9, and 9.3-31.1 µmol/L in boys, girls, and total population respectively. Serum zinc concentrations were comparable in boys and girls (17.5 ± 5.3 µmol/L vs. 17.2 ± 5.6 µmol/L, p=0.242). The dietary zinc intake of 7.6% (4.9% boys and 10.2% girls, p<0.01) was lower than the estimated average requirement. CONCLUSIONS: This study presents pediatric reference values for serum zinc concentrations, values that could help diagnose and manage zinc deficiency in pediatrics.

Prevalence of hypo- and hypermagnesemia in an Iranian urban population.

BACKGROUND: Magnesium (Mg) plays an important role in metabolic processes and its deficiency or excess could adversely affect metabolism. Although magnesium deficiency and excess is associated with a variety of medical conditions, the prevalence of hypo- and hypermagnesemia have not been reported in an Iranian urban population. SUBJECTS AND METHODS: This cross-sectional study was performed on 1558 subjects (754 males and 804 females), randomly selected from among participants of the Tehran Lipid and Glucose Study (TLGS). Serum Mg level was measured by flame atomic absorption spectrophotometry. Hypo- and hypermagnesemia were defined by serum Mg < 0.75 mmol/L and Mg>1.04 mmol/L, respectively, and sub-optimal serum Mg concentrations were defined by serum Mg < 0.8 mmol/L. RESULTS: The prevalence of hypomagnesemia was 4.6% in the total population, being more prevalent in females (6.0%) compared to males (3.2%) (p < 0.05). The overall prevalence of hypermagnesemia was 3.0% and it was more prevalent in males (3.2%) than females (2.7%) (p < 0.05). Sub-optimal Mg levels were found in 14.6% of the total population. CONCLUSIONS: The data show a relatively high prevalence of abnormal levels of serum Mg, among a general population; levels which may contribute to the pathophysiology of several diseases.

Pediatric reference values for serum magnesium levels in Iranian subjects.

Magnesium (Mg), an essential element, plays important roles in many physiological functions. Mg deficiency is associated with insulin resistance, cardiovascular disease, and disorders of the nervous system. The aim of this study was to determine reference values for serum Mg concentration in pediatrics. Serum Mg level was measured by flame atomic absorption spectrophotometry in 306 subjects (141 boys and 165 girls), aged 3-19 years, selected from among participants of the Tehran Lipid and Glucose Study. The International Federation of Clinical Chemistry guidelines (IFCC) and the robust method were used for determining reference values for sample sizes greater or less than 120 subjects respectively. The 95% reference values for serum Mg concentrations were 0.76-1.0, 0.75-1.0, and 0.76-0.99 mmol/L in boys, girls, and the all subjects respectively. According to the reference values obtained in this study, the prevalences of hypo- and hypermagnesemia, were 5.9% and 5.6% respectively. In conclusion, the current study presents pediatric reference values for serum Mg levels derived from a randomly selected healthy population, values which could be instrumental in detecting serum Mg abnormalities.

The influence of cigarette and qalyan (hookah) smoking on serum nitric oxide metabolite concentration.

OBJECTIVE: To assess the effect of exposure to cigarette and qalyan (hookah) smoking on serum nitric oxide (NO) metabolites (NO(x)) concentration. MATERIAL AND METHODS: Fasting serum NO(x) was measured by the Griess method in 333 men free of diabetes, hypertension and cardiovascular disease selected from participants of the Tehran Lipid and Glucose Study. Subjects were classified into active and passive cigarette smokers and they were age-matched with the non-smoker groups (n = 93/group). Twenty-seven qalyan smokers were also included in the study with their age-matched controls. RESULTS: Multivariable-adjustment serum NO(x) values were compared between groups by analysis of covariance. Serum NO(x) was significantly higher (p < 0.05) in the active smokers [28.9 micromol/L (95% CI 26.2-32.0)] compared to nonsmokers [24.1 micromol/L (95% CI 21.8-26.7)]. A positive correlation was found between serum NO(x) and the number of cigarettes smoked per day (r = 0.222, p < 0.05). Qalyan smokers had higher serum NO(x) levels compared to the non-smoker controls [34.3 micromol/L (95% CI 27.8-42.3) vs. 22.5 micromol/L (95% CI 18.4-27.6), p < 0.01]. CONCLUSION: Active cigarette and qalyan smoking are associated with high serum NO(x) levels.

Low serum magnesium levels in elderly subjects with metabolic syndrome.

This study aims at determining possible association between serum magnesium (Mg) concentrations and metabolic syndrome (MetS) in elderly subjects. Subjects were 137 men and women aged 60 to 90 years, selected from among participants of the Tehran Lipid and Glucose Study after excluding those taking medications for hypertension and dyslipidemia. Serum Mg levels were measured by atomic absorption spectrometry and MetS was defined according to ATP III criteria. The overall prevalence of MetS was 43.8%. Among MetS components, only plasma glucose showed a negative correlation with serum Mg concentrations (r = -0.194, p = 0.024). Subjects with MetS had significantly lower serum Mg concentrations compared with non-MetS ones (2.09 +/- 0.03 vs. 2.18 +/- 0.03 mg/dL, p = 0.033) even after adjustments with MetS components except for hyperglycemia (2.04 +/- 0.06 vs. 2.20 +/- 0.05 mg/dL, p = 0.011). However, after adjustment for hyperglycemia per se or along with the other MetS components, the significant difference between serum Mg levels in subjects with and without MetS disappeared. In conclusion, serum Mg level is diminished in elderly subjects with MetS, and hyperglycemia may play dominant role in this decrease; however, the results do not clarify whether the low serum Mg level is a consequence of hyperglycemia or is a risk factor contributing to its development.