Disposable stochastic sensors for fast analysis of ibuprofen, ketoprofen, and flurbiprofen in their topical pharmaceutical formulations.

Three disposable stochastic sensors based on maltodextrin (dextrose equivalent = 4-7) and nanostructures (copper monolayer, carbon monolayer and carbon-copper composite layer) deposited using cold plasma on copy paper were proposed for the fast analysis of ibuprofen, ketoprofen and flurbiprofen in pharmaceutical formulation samples. The widest linear concentration ranges recorded were: for ibuprofen 1 fmol/L - 1 mmol/L when the disposable stochastic sensor based on carbon monolayer was used, for ketoprofen 1 fmol/L - 1 mmol/L when the disposable stochastic sensors based on copper monolayer and carbon-copper composite layer were used, and for flurbiprofen 1 fmol/L - 10 mmol/L when the disposable stochastic sensor based on carbon-copper composite layer was used. The lowest limit of detection recorded for each non-steroidal anti-inflammatory drug was 1 fmol/L.

2D disposable stochastic sensors for molecular recognition and quantification of maspin in biological samples.

Three disposable stochastic sensors using nanolayer deposition of a graphene nanocomposite comprising graphene nanoparticles and gold nanoparticles, on different supports: silk, plastic, and paper, and modified with chitosan, were characterized and validated for molecular recognition and quantification of maspin in biological samples. Very low limits of determination (of pg mL-1 magnitude order) were recorded (5.12 pg mL-1 for the sensor based on silk at pH 7.40 and on copy paper at pHs 3.00 and 7.40; 16 ng mL-1 at pH 7.40 for the sensor based on plastic, 41.00 pg mL-1 for the sensor based on silk at pH 3.00, and 204.00 pg mL-1 for the sensor based on plastic, at pH 3.00), with wide linear concentration ranges (5.12 × 10-12-2.00 × 10-6 g mL-1 for the sensors based on silk at pH 7.40, and on copy paper at pH 3.00; 5.12 × 10-12-8.00 × 10-7 g mL-1 for the sensor based on copy paper at pH 7.40; 1.60 × 10-8-2.00 × 10-6 g mL-1 for the sensor based on plastic at pH 7.40; 4.10 × 10-14-2.00 × 10-6 g mL-1 for the sensor based on silk, at pH 3.00; and 2.04 × 10-13-8.00 × 10-7 g mL-1 for the sensor based on plastic at pH 3.00) allowing the molecular recognition and quantification of maspin in healthy people and patients with gastric cancer, when a potential of 125 mV vs. Ag/AgCl was applied. The recoveries of maspin in whole blood, saliva, urine, and tissue samples were higher than 95.00%, with a relative standard deviation lower than 1.0%.

Disposable stochastic sensors obtained by nanolayer deposition of copper, graphene, and copper-graphene composite on silk for the determination of isocitrate dehydrogenases 1 and 2.

Three disposable stochastic sensors designed using nanolayer deposition of copper (Cu), graphene (GR), and copper-graphene (Cu-GR) composite on the silk textile, as substrate, were modified with chitosan (n=371-744), for biomedical analysis. Isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) served as model analytes for molecular recognition and quantification in biological samples such as whole blood and brain tumor tissue samples. The best sensitivities (3.77×107s µg mL-1 for IDH1, and 1.88×107s µg mL-1 for IDH2) and the lowest limits of quantification (10-2fg mL-1 for IDH1, and 5×10-2fg mL-1 for IDH2) for both IDH1 and IDH2 were recorded for the disposable stochastic sensors based on chitosan/graphene nanolayer. Very good correlations between the screening method based on disposable stochastic sensors and enzyme-linked immunosorbent assay (ELISA) were obtained; this was also proved by the results obtained using the paired t-test.

Smart Portable Device Based on the Utilization of a 2D Disposable Paper Stochastic Sensor for Fast Ultrasensitive Screening of Food Samples for Bisphenols.

Since the determination of the high toxicity of bisphenol A, alternative structures for bisphenols have been synthesized, resulting in bisphenols C, E, F, S, and Z. These bisphenols have replaced bisphenol A in plastic bottles, toys, and cans used for preserving food. Later, the toxicity and negative effects of all of these bisphenols on people's health were proven. Therefore, there is a need for a fast ultrasensitive screening method that is able to detect the presence of these bisphenols in any condition directly from food samples. This paper presented a disposable device based on the utilization of a 2D disposable paper stochastic sensor for the fast ultrasensitive screening of food samples for bisphenols A, C, E, F, S, and Z. The 2D disposable sensor was obtained by the deposition of graphene and silver nanolayers on paper using cold plasma. Furthermore, the active side of the sensor was modified using 2,3,7,8,12,13,17,18-octaethyl-21H,23H Mn porphyrin. The limits of quantification of these bisphenols were 1 fmol L-1 for bisphenols C and E, 10 fmol L-1 for bisphenols A and F, 10 pmol L-1 for bisphenol S, and 1 pmol L-1 for bisphenol Z. The recoveries of these bisphenols in milk, canned fruits, vegetables, and fish were higher than 99.00% with RSD (%) values lower than 1.50%.

Sensitive Detection of Heregulin-α from Biological Samples Using a Disposable Stochastic Sensor Based on Plasma Deposition of GNPs-AgPs' Nanofilms on Silk.

A composite material comprised of graphene nanoplatelet and silver particles (GNPs-AgPs) was used for the deposition of GNPs-AgPs' nanofilms with cold plasma on silk. α-Cyclodextrin was used as a modifier of the active surface of the disposable sensor. The disposable stochastic sensor was used in screening tests for the assay of heregulin-α in whole blood and tissue samples. The disposable stochastic sensor showed a low limit of determination (4.10 fg mL-1) and can be used with high sensitivity on a wide concentration range (4.10 fg mL-1-0.04 µg mL-1). The screening method was validated against ELISA when good correlations (confirmed also by the t-test) were obtained.

Disposable Stochastic Sensors Based on Nanolayer Deposition(s) of Silver and AgC Composite on Plastic for the Assay of α-amylase in Whole Blood and Saliva.

Nanolayer deposition(s) of Ag and AgC composite on a plastic substrate was used to design disposable stochastic sensors. Three shapes of nanocoatings were tested. The first shape was obtained by deposition of a nanofilm of Ag on the plastic material; the second shape was obtained by deposition of a composite AgC nanolayer on the plastic material; the third shape was obtained by nanolayer deposition of a composite material of AgC on the top of the Ag nanofilm deposited on the plastic material. α-Cyclodextrin was used to modify the active surface of the sensor. Wide linear concentration ranges were obtained as follows: for de-assay of α-amylase in whole blood: 1.00 × 10-7-1.00 × 103 U mL-1 and for the assay of α-amylase in saliva: 1.5 × 10-15-1.5 × 102 U mL-1. α-Amylase was reliably determined from whole blood and saliva samples using the proposed disposable stochastic sensors.

Fast screening method for molecular recognition of islet amyloid polypeptide from whole blood samples collected from diabetic patients with disposable stochastic sensors obtained by nanolayer, and nanolayer by nanolayer deposition using cold plasma.

Nanolayer and nanolayer by nanolayer deposition of nanofilms of Ag and C using cold plasma in sequences (Ag, Ag-C, Ag-Ag-C), on porous paper, were used to design three disposable stochastic sensors for the assay of amyloid polypeptide from whole blood. The nanofilms were modified with α-cyclodextrin. The test developed using the nanofilm-based disposable stochastic sensors is used for early detection of diabetes. The wider linear concentration range (1.00 × 10-6-1.00 ng mL-1) and the lower limit of quantification (1.00 × 10-6ng mL-1) were obtained using the disposable stochastic sensors based on Ag-C and Ag-Ag-C, while the highest sensitivity (3.19 × 104 s-1/µg mL-1) was recorded using the disposable stochastic sensor based on Ag-Ag-C. The screening methods were fully validated using whole blood samples from confirmed patients, when the recovery of the islet amyloid polypeptide was higher than 98.00%. Graphical abstract.

Copper Bead Therapy in Severe Bone Infection: A Rabbit Tibial Model.

OBJECTIVE: We investigated the benefits of a local preventive therapy based on copper beads against severe bone infection using a rabbit open tibial fracture model. MATERIALS AND METHODS: Cotton mesh balls soaked in a very high concentration of Staphylococcus aureus ATCC 6538 culture were inoculated in drilled holes of the tibiae of treated and control groups. The treated group was also implanted with small copper beads simultaneously, as prevention therapy. RESULTS: Survival rate in the treated group was 67% compared with 25% in the control group (difference 40%, for a 95% confidence interval: 40%, 93.4%). The few remaining animals in the control group had bone lesions which developed into osteomyelitis, while the tibiae of treated group had clear signs of reparatory processes. Sixty days after inoculation, signs of local-only toxicity were observed in healthy tibia of a separate non-infected control group. Drawbacks of copper toxicity were weighed against the threat of septicaemia and also against prolonged use of powerful systemic antibiotic medications in severe bone contamination. CINICAL SIGNIFICANCE: It was found that the proposed therapy prevented septicaemia and the spread of infection, and it also induced reparatory processes. The findings of this study may be relevant in antisepsis of open fractures in less appropriate medical settings (such as military camps or remote locations), as well as in severe bone infections.

The influence of foreign body surface area on the outcome of chronic osteomyelitis.

Reproducible animal models of osteomyelitis close to the clinical scenario are difficult to obtain as the animals either die shortly after inoculation of bacteria or the bone cures itself of infection. Additional materials used as foreign bodies offer increased chances for localized infection due to bacterial attachment and are closer to clinical pathology. Through in vivo experimentation we investigated here the influence of surface area of a series of foreign bodies on the final outcome of the animal model, in terms of reproducibility, survival rate and time necessary for onset of chronic disease. Stainless steel Kirschner wire segments, stainless steel balls and cotton meshes were employed for this purpose. The clinical, microbiological, radiological and histological results obtained were compared with the simple case where no foreign body was used. The follow-up period was 57days. The cotton meshes, which had the highest surface area, were observed to provide the best outcome, with the lowest disease onset time interval (of 1week earlier than the others), the highest survival (of 90%) and disease reproduction rate (90%). The only clinical pattern of the mesh group rabbits was short lived inflammation while the other rabbits presented also some other clinical signs such as rhinorrheas, abscesses, rush and/or dyspnea. Moreover, this model is the most suitable for further treatment studies, as the cotton meshes could be easily removed after disease onset, without any intervention on the bone. This is important, as the treatment would address the bacteria present within the bone parts (marrow, cortex, periosteum etc.) not those forming the biofilm.

Nanostructured materials detect epidermal growth factor receptor, neuron specific enolase and carcinoembryonic antigen.

New nanostructured materials based on thin films of Cu and Ni deposited on textile material (veil), as well as gold nanostructured microspheres were used for the design of new stochastic sensors. The stochastic sensors were able to detect simultaneously a panel of biomarkers comprising epidermal growth factor receptor, neuron specific enolase, and carcinoembryonic antigen from whole blood samples with high reliabilities - recovery tests higher than 97.00%, with a RSD (%) lower than 0.1%. The stochastic sensors had shown high sensitivities and low determination levels for the detection of the proposed panel of biomarkers making early detection of lung cancer possible by fast screening of whole blood.

Implant microparticles--a new concept for non-invasive cancer therapy.

Some progress in cancer research was possible in recent years mainly due to important advances in nanotechnology. However, clinical use of nanomaterials is still hindered by limitations. In search of better performance and control of inoculated materials, the efficiency and toxicity of SBBC implant particles was assessed. B16 tumoral cells (murine melanoma) were subjected to SBCC particles using in vitro and in vivo experimental models. In vitro experiments concerning the growth inhibition of tumoral cells using SBCC particles were performed by Flow Cytometry and by MTT Assay. In vivo experimental model (C57BL/6 mice) was used to complete this investigation: weight, viability and tumoral dimension were monitored. An anti-proliferative activity on B16 tumoral cells and an ability to produce apoptosis were observed. A reduction of tumoral volume and a 54% survival rate in the treated animals compared to the controls was obtained. Our preliminary results showed that the SBCC implants were effective against B16 melanoma cells, while there is no toxicity associated.

Antimicrobial activity of copper and silver nanofilms on nosocomial bacterial species.

Contaminated surfaces are possible vehicles in infection transmission. It is known that both Copper (Cu) and Silver (Ag) efficiently inactivate microbes by direct contact. Aiming at using these metals for benefitting from their antimicrobial effect, but to avoid subsequent toxic effects, we evaluated the antimicrobial activity of nanometric thin Silver and Copper films covering less expensive materials. Using a modified version of the Japan Industrial Standard JIS Z 2801:2000, we demonstrated the antimicrobial activity of the surfaces covered with metal ions nanofilms on microorganisms possibly involved in nosocomial infections and on Bacillus anthracis, bacteria with possible implication in bioterrorist attacks. Copper covered surfaces proved to have better antimicrobial activity than Silver surfaces. Silver covered surfaces showed better activity on Gram negative bacteria than on Gram positive cocci. Going deeper with studies on antimicrobial effects using new methods with better direct and/or functional discriminatory capacity is needed in order to provide additional information on the mechanisms of Silver and Copper nanofilms antimicrobial activity.