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.
A novel device was developed for the future detection of gastrointestinal bleeding.
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.
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 (1015-1019 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.
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.
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IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UL, UM, UPUK
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.
•Multiplexed detection of four different metabolite biomarkers using an integrated-circuit-based handheld device with capability to detect and quantify in <2 min.•The metabolites (choline, xanthine, cholesterol and sarcosine), detected in bio-fluids,are implicated in ischaemia and prostate cancer.•The CMOS-chip, with isolated micro-wells, allows metabolite-assays without cross-contamination of assay reagents and signal cross-talk.•A handheld device, with an Android-based user-interface application for phones and tablets, is capable of being powered through a simple micro-USB.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
An imatinib intermediate, 6-methyl-N-4-(pyridin-3-yl)pyrimidin-2-ylbenzene-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.
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.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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
H 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 Hg
ions with a nano-molar detection limit of 0.69 nM. Finally, the sensor PTB-1 was applied successfully for the intracellular detection of Hg
ions in a HepG2 liver cell line, which was monitored by the use of confocal imaging techniques.
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.
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