As the major redox couple and nonprotein thiol source in human tissues, the level of glutathione (GSH) has been a concern for its relation with many diseases. However, the similar physical and chemical properties of interference molecules such as cysteine (Cys) and homocysteine (Hcy) make discriminative detection of GSH in complex biological fluids challenging. Here we report a novel surface-enhanced Raman scattering (SERS) platform, based on silver-nanoparticleembedded porous silicon disks (PSDs/Ag) substrates for highly sensitive and selective detection of GSH in biofluids. Silver nanoparticles (AgNPs) were reductively synthesized and aggregated directly into pores of PSDs, achieving a SERS enhancement factor (EF) up to 2.59 × 10 7 . Ellman's reagent 5,5′-ditho-bis (2-nitrobenzoic acid) (DTNB) was selected as the Raman reactive reporting agent, and the GSH quantification was determined using enzymatic recycling method, and allowed the detection limit of GSH to be down to 74.9 nM using a portable Raman spectrometer. Moreover, the significantly overwhelmed enhancement ratio of GSH over other substances enables the discrimination of GSH detection in complex biofluids.
We report an inkjet-printed microscale magnetic structure that can be integrated on regular glass slides for the immunomagnetic screening of rare Circulating Tumor Cells (CTCs). CTCs detach from the primary tumor site, circulate with the bloodstream, and initiate the cancer metastasis process. Therefore, a liquid biopsy in the form of capturing and analyzing CTCs may provide key information for cancer prognosis and diagnosis. Inkjet printing technology provides a non-contact, layer-by-layer and mask-less approach to deposit defined magnetic patterns on an arbitrary substrate. Such thin film patterns, when placed in an external magnetic field, significantly enhance the attractive force in the near-field close to the CTCs to facilitate the separation. We demonstrated the efficacy of the inkjet-print micromagnet array integrated immunomagnetic assay in separating COLO205 (human colorectal cancer cell line) from whole blood samples. The micromagnets increased the capture efficiency by 26% compared with using plain glass slide as the substrate.
Previously disclosed dihydropyrazolopyrimidines are potent and selective blockers of I(Kur) current. A potential liability with this chemotype is the formation of a reactive metabolite which demonstrated covalent binding to protein in vitro. When substituted at the 2 or 3 position, this template yielded potent I(Kur) inhibitors, with selectivity over hERG which did not form reactive metabolites. Subsequent optimization for potency and PK properties lead to the discovery of ((S)-5-(methoxymethyl)-7-(1-methyl-1H-indol-2-yl)-2-(trifluoromethyl)-4,7-dihydropyrazolo[1,5-a]pyrimidin-6-yl)((S)-2-(3-methylisoxazol-5-yl)pyrrolidin-1-yl)methanone (13j), with an acceptable PK profile in preclinical species and potent efficacy in the preclinical rabbit atrial effective refractory period (AERP) model.
We demonstrate a MEMS micromirror enabled handheld confocal imaging probe for portable oral cancer detection, where a comparatively large field of view (FOV) was generated through the programmable Lissajous scanning pattern of the MEMS micromirror. Miniaturized handheld MEMS confocal imaging probe was developed, and further compared with the desktop confocal prototype under clinical setting. For the handheld confocal imaging system, optical design simulations using CODE V R R shows the lateral and axial resolution to be 0.98 μm and 4.2 μm, where experimental values were determined to be 3 μm and 5.8 μm, respectively, with a FOV of 280 μm × 300 μm. Fast Lissajous imaging speed up to 2 fps was realized with improved Labview and Java based real-time imaging software. Properties such as 3D imaging through autofocusing and mosaic imaging for extended lateral view (6 mm × 8 mm) were examined for carcinoma real-time pathology. Neoplastic lesion tissues of giant cell fibroma and peripheral ossifying fibroma, the fibroma inside the paraffin box and ex vivo gross tissues were imaged by the bench-top and handheld imaging modalities, and further compared with commercial microscope imaging results. The MEMS scanner-based handheld confocal imaging probe shows great promise as a potential clinical tool for oral cancer diagnosis and treatment.
We present the design and integration of a two-dimensional (2D) plasmonic nanogratings structure on the electrode of colloidal quantum dot-based light-emitting diodes (QDLEDs) as a compact light source towards arrayed on-chip imaging of tumor cells. Colloidal quantum dots (QDs) were used as the emission layer due to their unique capabilities, including multicolor emission, narrow bandwidth, tunable emission wavelengths, and compatibility with silicon fabrication. The nanograting, based on a metal-dielectric-metal plasmonic waveguide, aims to enhance the light intensity through the resonant reflection of surface plasmon (SP) waves. The key parameters of plasmonic nanogratings, including periodicity, slit width, and thicknesses of the metal and dielectric layers, were designed to tailor the frequency bandgap such that it matches the wavelength of operation. We fabricated QDLEDs with the integrated nanogratings and demonstrated an increase in electroluminescence intensity, measured along the direction perpendicular to the metal electrode. We found an increase of 34.72% in QDLED electroluminescence intensity from the area of the pattern and an increase of 32.63% from the photoluminescence of QDs deposited on a metal surface. We performed ex vivo transmission-mode microscopy to evaluate the nucleus-cytoplasm ratios of MDA-MB 231 cultured breast cancer cells using QDLEDs as the light source. We showed wavelength dependent imaging of different cell components and imaging of cells at higher magnification using enhanced emission from QDLEDs with integrated plasmonic nanogratings.
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