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1.
Analyst ; 149(4): 1081-1089, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38204338

RESUMO

Gastrointestinal bleeding (GIB) is a serious medical condition, which requires immediate attention to establish the cause of the bleeding. Here, we present the development of a miniaturised electrochemical impedance spectroscopy (EIS) device for the detection of GIB. The device performs EIS measurements up to 100 kHz. Following the development of an immunosensor for haemoglobin (Hb) on screen printed electrodes, the EIS device was used for detecting Hb as an early indication of bleeding. The sensor was able to detect Hb in a redox solution in a linear range between 5 µg mL-1 and 60 µg mL-1, with a limit of detection of 13.3 µg mL-1. It was also possible to detect Hb in simulated intestinal fluid, without the need for a redox solution, within a range of 10 µg mL-1 to 10 mg mL-1 with a limit of detection of 2.31 mg mL-1. The miniature EIS device developed in this work is inexpensive, with an estimated cost per unit of £30, and has shown a comparable performance to existing commercial tools, demonstrating its potential to be used in the future as an ingestible sensor to detect GIB. All these measurements were carried out in a purpose built flow cell with supporting hardware electronics outside the cell. Integration of the hardware and the sensing electrodes was demonstrated in pill form. This pill after integration sampling fluidics has potential to be used in detecting gastrointestinal bleeding.


Assuntos
Técnicas Biossensoriais , Hemoglobina Falciforme , Humanos , Técnicas Biossensoriais/métodos , Imunoensaio/métodos , Espectroscopia Dielétrica , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/diagnóstico , Eletrodos , Limite de Detecção , Técnicas Eletroquímicas/métodos , Ouro/química
2.
Nanotechnology ; 26(13): 135701, 2015 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-25751635

RESUMO

The capability of scanning microwave microscopy for calibrated sub-surface and non-contact capacitance imaging of silicon (Si) samples is quantitatively studied at broadband frequencies ranging from 1 to 20 GHz. Calibrated capacitance images of flat Si test samples with varying dopant density (10(15)-10(19) atoms cm(-3)) and covered with dielectric thin films of SiO2 (100-400 nm thickness) are measured to demonstrate the sensitivity of scanning microwave microscopy (SMM) for sub-surface imaging. Using standard SMM imaging conditions the dopant areas could still be sensed under a 400 nm thick oxide layer. Non-contact SMM imaging in lift-mode and constant height mode is quantitatively demonstrated on a 50 nm thick SiO2 test pad. The differences between non-contact and contact mode capacitances are studied with respect to the main parameters influencing the imaging contrast, namely the probe tip diameter and the tip-sample distance. Finite element modelling was used to further analyse the influence of the tip radius and the tip-sample distance on the SMM sensitivity. The understanding of how the two key parameters determine the SMM sensitivity and quantitative capacitances represents an important step towards its routine application for non-contact and sub-surface imaging.

3.
J Fluoresc ; 24(6): 1563-70, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25209201

RESUMO

An amidine based chemosensor AM-1 was synthesized and characterized by various spectroscopic (FT-IR, (1)H-NMR and mass) data and elemental analyses. Sensor AM-1 exhibited high selectivity and sensitivity towards Fe(3+), Fe(2+) and Cu(2+) in the presence of other surveyed ions (such as Sr(2+), Cr(3+), Co(2+), Ni(2+), Zn(2+), Ag(+), Al(3+), Ba(2+), Ca(2+), Cd(2+), Cs(+), Hg(2+), K(+), Li(+), Mg(2+), Mn(2+), Na(+) and Pb(2+)) with a distinct naked-eye detectable color change and a shift in the absorption band. Moreover, the emission of AM-1 was quenched selectively only in the presence of Fe(3+).

4.
Clin Med (Lond) ; 23(2): 157-163, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36958833

RESUMO

During the coronavirus 2019 (COVID-19) pandemic, the implementation of non-contact infrared thermometry (NCIT) became an increasingly popular method of screening body temperature. However, data on the accuracy of these devices and the standardisation of their use are limited. In the current study, the body temperature of non-febrile volunteers was measured using infrared (IR) thermography, IR tympanic thermometry and IR gun thermometry at different facial feature locations and distances and compared with SpotOn core-body temperature. Poor agreement was found between all IR devices and SpotOn measurements (intra-class correlation coefficient <0.8). Bland-Alman analysis showed the narrowest limits of agreement with the IR gun at 3 cm from the forehead (bias = 0.19°C, limits of agreement (LOA): -0.58°C to 0.97°C) and widest with the IR gun at the nose (bias = 1.40°C, LOA: -1.15°C to 3.94°C). Thus, our findings challenge the established use of IR thermometry devices within hospital settings without adequate standard operating procedures to reduce operator error.


Assuntos
COVID-19 , Termometria , Humanos , Temperatura Corporal , Temperatura , Termometria/métodos , COVID-19/diagnóstico , Voluntários
5.
Int J Biol Macromol ; 175: 270-280, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33561462

RESUMO

The burden of obesity is increasing all over the world. Except for Orlistat, no effective anti-obesity drug is currently available. Therefore, a search for the new anti-obesity compound is need of time. This study demonstrates macromolecular interaction and inhibitory effect of pentacyclic triterpenoids (PTT) on pancreatic lipase (PL). In the present study PTTs from endophytic Colletotrichum gigasporum were found to show significant inhibitory activity against PL with IC50 of 16.62 ± 1.43 µg/mL. The PTT isolated through bioassay-guided isolation showed a dose-dependent (R2 = 0.915) inhibition against porcine PL and the results were comparable with the standard (Orlistat). Based on inhibition kinetic data, the gradual increase in Km (app) with increasing PTT concentration indicated that the mode of interaction of PTT with PL was a competitive type, and it directly competed with the substrate (pNPB) for the active site of PL. In vivo studies in Wistar rats at the oral dose (100 mg/kg body weight) of PTT significantly decreased (p < 0.05) incremental plasma triglyceride levels as compared to group B and TG absorption was down-regulated up to 49.18% vis a vis group D animals. The isolated PTT was identified as lupeol based on chromatographic and spectral data. The endophytic isolate was identified as Colletotrichum gigasporum based on morphology and ITS gene sequencing. The present study indicated that PTT had the potential to be used as a natural PL inhibitor in the treatment of obesity and the isolated endophyte can be a valuable bioresource for it.


Assuntos
Colletotrichum/metabolismo , Lipase/antagonistas & inibidores , Triterpenos Pentacíclicos/farmacologia , Animais , Fármacos Antiobesidade/farmacologia , Domínio Catalítico , Endófitos , Inibidores Enzimáticos/farmacologia , Humanos , Concentração Inibidora 50 , Cinética , Lipase/química , Lipase/metabolismo , Masculino , Estrutura Molecular , Obesidade/tratamento farmacológico , Orlistate/farmacologia , Pâncreas/metabolismo , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/metabolismo , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Suínos , Triterpenos/farmacologia
6.
Microsyst Nanoeng ; 7: 21, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34567735

RESUMO

There is a global unmet need for rapid and cost-effective prognostic and diagnostic tools that can be used at the bedside or in the doctor's office to reduce the impact of serious disease. Many cancers are diagnosed late, leading to costly treatment and reduced life expectancy. With prostate cancer, the absence of a reliable test has inhibited the adoption of screening programs. We report a microelectronic point-of-care metabolite biomarker measurement platform and use it for prostate cancer detection. The platform, using an array of photodetectors configured to operate with targeted, multiplexed, colorimetric assays confined in monolithically integrated passive microfluidic channels, completes a combined assay of 4 metabolites in a drop of human plasma in under 2 min. A preliminary clinical study using l-amino acids, glutamate, choline, and sarcosine was used to train a cross-validated random forest algorithm. The system demonstrated sensitivity to prostate cancer of 94% with a specificity of 70% and an area under the curve of 0.78. The technology can implement many similar assay panels and hence has the potential to revolutionize low-cost, rapid, point-of-care testing.

7.
Biosens Bioelectron ; 122: 88-94, 2018 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-30245326

RESUMO

Metabolites, the small molecules that underpin life, can act as indicators of the physiological state of the body when their abundance varies, offering routes to diagnosis of many diseases. The ability to assay for multiple metabolites simultaneously will underpin a new generation of precision diagnostic tools. Here, we report the development of a handheld device based on complementary metal oxide semiconductor (CMOS) technology with multiple isolated micro-well reaction zones and integrated optical sensing allowing simultaneous enzyme-based assays of multiple metabolites (choline, xanthine, sarcosine and cholesterol) associated with multiple diseases. These metabolites were measured in clinically relevant concentration range with minimum concentrations measured: 25 µM for choline, 100 µM for xanthine, 1.25 µM for sarcosine and 50 µM for cholesterol. Linking the device to an Android-based user interface allows for quantification of metabolites in serum and urine within 2 min of applying samples to the device. The quantitative performance of the device was validated by comparison to accredited tests for cholesterol and glucose.


Assuntos
Técnicas Biossensoriais/instrumentação , Dispositivos Lab-On-A-Chip , Sistemas Automatizados de Assistência Junto ao Leito , Colesterol/sangue , Colesterol/urina , Colina/sangue , Colina/urina , Desenho de Equipamento , Humanos , Masculino , Óxidos/química , Sarcosina/sangue , Sarcosina/urina , Semicondutores , Xantina/sangue , Xantina/urina
8.
Commun Biol ; 1: 175, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30374465

RESUMO

Mechanical signaling involved in molecular interactions lies at the heart of materials science and biological systems, but the mechanisms involved are poorly understood. Here we use nanomechanical sensors and intact human cells to provide unique insights into the signaling pathways of connectivity networks, which deliver the ability to probe cells to produce biologically relevant, quantifiable and reproducible signals. We quantify the mechanical signals from malignant cancer cells, with 10 cells per ml in 1000-fold excess of non-neoplastic human epithelial cells. Moreover, we demonstrate that a direct link between cells and molecules creates a continuous connectivity which acts like a percolating network to propagate mechanical forces over both short and long length-scales. The findings provide mechanistic insights into how cancer cells interact with one another and with their microenvironments, enabling them to invade the surrounding tissues. Further, with this system it is possible to understand how cancer clusters are able to co-ordinate their migration through narrow blood capillaries.

9.
Sci Rep ; 7: 41206, 2017 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-28155918

RESUMO

The alarming increase of pathogenic bacteria that are resistant to multiple antibiotics is now recognized as a major health issue fuelling demand for new drugs. Bacterial resistance is often caused by molecular changes at the bacterial surface, which alter the nature of specific drug-target interactions. Here, we identify a novel mechanism by which drug-target interactions in resistant bacteria can be enhanced. We examined the surface forces generated by four antibiotics; vancomycin, ristomycin, chloroeremomycin and oritavancin against drug-susceptible and drug-resistant targets on a cantilever and demonstrated significant differences in mechanical response when drug-resistant targets are challenged with different antibiotics although no significant differences were observed when using susceptible targets. Remarkably, the binding affinity for oritavancin against drug-resistant targets (70 nM) was found to be 11,000 times stronger than for vancomycin (800 µM), a powerful antibiotic used as the last resort treatment for streptococcal and staphylococcal bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Using an exactly solvable model, which takes into account the solvent and membrane effects, we demonstrate that drug-target interactions are strengthened by pronounced polyvalent interactions catalyzed by the surface itself. These findings further enhance our understanding of antibiotic mode of action and will enable development of more effective therapies.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana/efeitos dos fármacos , Staphylococcus/efeitos dos fármacos , Streptococcus/efeitos dos fármacos , Proteínas de Bactérias/química , Fenômenos Biomecânicos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Glicopeptídeos/farmacologia , Lipoglicopeptídeos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Ligação Proteica , Ristocetina/farmacologia , Staphylococcus/metabolismo , Streptococcus/metabolismo , Propriedades de Superfície , Vancomicina/análogos & derivados , Vancomicina/farmacologia
10.
Dalton Trans ; 46(41): 14201-14209, 2017 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-28990631

RESUMO

The pyridine substituted thiourea derivative PTB-1 was synthesized and characterized by spectroscopic techniques as well as by single crystal X-ray crystallography. The metal ion sensing ability of PTB-1 was explored by various experimental (naked-eye, UV-Vis, fluorescence, mass spectrometry and 1H NMR spectroscopy) and theoretical (B3LYP/6-31G**/LANL2DZ) methods. PTB-1 exhibited a highly selective naked-eye detectable color change from colorless to dark brown and UV-Vis spectral changes for the detection of Ag+ with a detection limit of 3.67 µM in aqueous medium. The detection of Ag+ ions was achieved by test paper strip and supported silica methods. In contrast, PTB-1 exhibited a 23-fold enhanced emission at 420 nm in the presence of Hg2+ ions with a nano-molar detection limit of 0.69 nM. Finally, the sensor PTB-1 was applied successfully for the intracellular detection of Hg2+ ions in a HepG2 liver cell line, which was monitored by the use of confocal imaging techniques.


Assuntos
Mercúrio/análise , Prata/análise , Tioureia/análogos & derivados , Água/química , Cristalografia por Raios X , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Íons/química , Limite de Detecção , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Microscopia Confocal , Conformação Molecular , Piridinas/química , Teoria Quântica , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Tioureia/química , Tioureia/metabolismo
11.
Nat Nanotechnol ; 10(10): 899-907, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26280409

RESUMO

Cantilever arrays have been used to monitor biochemical interactions and their associated stress. However, it is often necessary to passivate the underside of the cantilever to prevent unwanted ligand adsorption, and this process requires tedious optimization. Here, we show a way to immobilize membrane receptors on nanomechanical cantilevers so that they can function without passivating the underlying surface. Using equilibrium theory, we quantitatively describe the mechanical responses of vancomycin, human immunodeficiency virus type 1 antigens and coagulation factor VIII captured on the cantilever in the presence of competing stresses from the top and bottom cantilever surfaces. We show that the area per receptor molecule on the cantilever surface influences ligand-receptor binding and plays an important role on stress. Our results offer a new way to sense biomolecules and will aid in the creation of ultrasensitive biosensors.


Assuntos
Proteínas Imobilizadas/metabolismo , Receptores de Superfície Celular/metabolismo , Ressonância de Plasmônio de Superfície/métodos , Animais , Antibacterianos/metabolismo , Camelídeos Americanos , Desenho de Equipamento , Fator VIII/metabolismo , HIV-1/imunologia , Humanos , Cinética , Modelos Moleculares , Ligação Proteica , Anticorpos de Domínio Único/imunologia , Ressonância de Plasmônio de Superfície/instrumentação , Propriedades de Superfície , Vancomicina/metabolismo , Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia
12.
Biosens Bioelectron ; 61: 612-7, 2014 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-24967750

RESUMO

An electronically active and spectral sensitive fluorescent "turn-on" chemosensor (BTP-1) based on the benzo-thiazolo-pyrimidine unit was designed and synthesized for the highly selective and sensitive detection of Fe(3+) from aqueous medium. With Fe(3+), the sensor BTP-1 showed a remarkable fluorescence enhancement at 554 nm (λex = 314 nm) due to the inhibition of photo-induced electron transfer. The sensor formed a host-guest complex in 1:1 stoichiometry with the detection limit down to 0.74 nM. Further, the sensor was successfully utilized for the qualitative and quantitative intracellular detection of Fe(3+) in two liver cell lines i.e., HepG2 cells (human hepatocellular liver carcinoma cell line) and HL-7701 cells (human normal liver cell line) by a confocal imaging technique.


Assuntos
Compostos Férricos/análise , Corantes Fluorescentes/química , Ferro/análise , Fígado/citologia , Tiazóis/química , Linhagem Celular , Sobrevivência Celular , Células Hep G2 , Humanos , Limite de Detecção , Microscopia de Fluorescência/métodos , Imagem Óptica/métodos , Espectrometria de Fluorescência/métodos
13.
Dalton Trans ; 43(35): 13299-306, 2014 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-25056090

RESUMO

An imatinib intermediate, 6-methyl-N-[4-(pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-diaminepyridopyrimidotoluidine (PPT-1), was developed for the colorimetric sensing of Cu(2+) ions in aqueous solution. With Cu(2+), the receptor PPT-1 showed a highly selective naked-eye detectable color change from colorless to red over the seventy other tested cations. The colorimetric sensing ability of PPT-1 was successfully utilized in the preparation of test strips and supported silica for the real samples analysis to detect Cu(2+) ions from 100% aqueous environment. Moreover, the iodide-sensing ability of receptor PPT-1 was explored among the ten examined anions.


Assuntos
Benzamidas/química , Cobre/análise , Iodetos/análise , Piperazinas/química , Pirimidinas/química , Água/análise , Colorimetria/métodos , Mesilato de Imatinib , Íons , Soluções/análise
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