Noninvasive methods for monitoring diabetes are being developed to eliminate the need for invasive finger-prick testing. Here, we propose the noninvasive detection of tear glucose using contact lenses that contain cerium oxide nanoparticles (CNPs). We chemically conjugated CNPs with glucose oxidase (GOx) using poly(ethylene glycol) (PEG) (CNP-PEG-GOx). GOx oxidizes glucose into hydrogen peroxide, which rapidly (∼1 min) reduces colorless Ce3+ to yellow Ce4+ with high sensitivity (>0.1 mM). Then, the yellow CNP-PEG-GOx can be analyzed to quantify the glucose concentration using a smartphone equipped with an image-processing algorithm. The CNP-PEG-GOx-laden contact lenses had physical properties similar to those of commercially available contact lenses and were nontoxic to human corneal cells and endothelial cells. When the CNP-PEG-GOx-laden contact lenses were placed on the eyes of diabetic rabbits, it was possible to measure the tear glucose levels. Interestingly, the lenses successfully detected glucose in human tear specimens and distinguished the diabetes status of patients. These findings suggest that the CNP-PEG-GOx-laden contact lenses could be used along with a smartphone-based image-processing algorithm to noninvasively monitor human tear glucose.
We present structural and molecular-contrast imaging of mouse brain tumors using photo-thermal optical coherence tomography (PT-OCT) in vivo. Based on strong PT response of gold nanostars, we demonstrate clear visualization of brain cancer margins.
The multilateral analysis of mouse electroencephalography (EEG) is essential for various fields such as neurology, preclinical research, and neural engineering. The systematic and quantitative analysis of visually evoked potential (VEP) elicited by the repeated flash stimuli provides a foundation for related applications. We confirm the experimental validation of the developed mouse EEG sensor through VEP analysis by successive two flash stimuli. The EEG signal by the first stimulus shows higher amplitude and more precise subdivision in temporal segmentation than second stimulation case. We have confirmed a high utilization of developed sensor for in vivo experiments, and we expect the results with the developed mouse EEG sensor could help enhancing the performance of related applications such as clinical system and brain-computer interface.
Optical-resolution photoacoustic microscopy (OR-PAM) has been studied to improve its imaging resolution and functional imaging modality without labeling on biology sample. However the use of high numerical aperture (NA) objective lens confines the field of view or the axial imaging range of OR-PAM. In order to obtain images at different layers, one needs to change either the sample position or the focusing position by mechanical scanning. This mechanical movement of the sample or the objective lens limits the scanning speed and the positioning precision. In this study, we propose a multi-depth PAM with a focus tunable lens. We electrically adjusted the focal length in the depth direction of the sample, and twice extended the axial imaging range up to 660 μm with the objective lens (20X, NA 0.4). The proposed approach can increase scanning speed and avoid step motor induced distortions during PA signal acquisitions without mechanical scanning in the depth direction. To investigate the performance of the multi-depth PAM system, we scanned a black human hair and the ear of a living nude mouse (BALB/c Nude). The obtained PAM images presented the volumetric rendering of black hair and the vasculature of the nude mouse.
Open-top light-sheet microscopy (OT-LSM) is a specialized microscopic technique for high throughput cellular imaging of large tissue specimens including optically cleared tissues by having the entire optical setup below the sample stage. Current OT-LSM systems had relatively low axial resolutions by using weakly focused light sheets to cover the imaging field of view (FOV). In this report, open-top axially swept LSM (OTAS-LSM) was developed for high-throughput cellular imaging with improved axial resolution. OTAS-LSM swept a tightly focused excitation light sheet across the imaging FOV using an electro tunable lens (ETL) and collected emission light at the focus of the light sheet with a camera in the rolling shutter mode. OTAS-LSM was developed by using air objective lenses and a liquid prism and it had on-axis optical aberration associated with the mismatch of refractive indices between air and immersion medium. The effects of optical aberration were analyzed by both simulation and experiment, and the image resolutions were under 1.6µm in all directions. The newly developed OTAS-LSM was applied to the imaging of optically cleared mouse brain and small intestine, and it demonstrated the single-cell resolution imaging of neuronal networks. OTAS-LSM might be useful for the high-throughput cellular examination of optically cleared large tissues.
Abstract A rapid and accurate molecular fluorescence imaging technique will greatly reduce cancer mortality by overcoming the detection limit of the naked eye in colonoscopy. Two imaging probes are reported that can be co‐used for colonoscopic diagnosis: a fluorescent molecular probe, cresyl violet–glutamic acid derivative, that ratiometrically switches between two fluorescent colors in response to the enzyme activity of λ‐glutamyltranspeptidase and an antibody quantum dot probe that is a conjugate of biocompatible AgInS 2 quantum dot with matrix metalloproteinase 14 antibodies. Validity of the probes is confirmed using human colon cancer cell lines, ex vivo mouse model tissues, and patient tumor colon tissues in which the tumor lesions are well‐visualized in less than five minutes. Co‐application of the two probes onto fresh colon tissues affords accurate visualization of carcinomas and also hyperplasia and adenoma regions. Fresh human colon adenoma tissues are also valuated, where the two probes show complementary diagnoses of cancer. Two‐photon microscopy shows the time‐dependent depth profiles of the two probes. Both rapidly permeate and populate most at 10–20 µm from the surface. Extensive toxicity studies are performed for the two probes at cellular level and also at the organ level using a small animal model.
The hippocampus is associated with memory and navigation, and the rodent hippocampus provides a useful model system for studying neurophysiology such as neural plasticity. Vascular changes at this site are closely related to brain diseases, such as Alzheimer's disease, dementia, and epilepsy. Vascular imaging around the hippocampus in mice may help to further elucidate the mechanisms underlying these diseases. Optical coherence tomography angiography (OCTA) is an emerging technology that can provide label-free blood flow information. As the hippocampus is a deep structure in the mouse brain, direct in vivo visualisation of the vascular network using OCTA and other microscopic imaging modalities has been challenging. Imaging of blood vessels in the hippocampus has been performed using multiphoton microscopy; however, labelling with fluorescence probes is necessary when using this technique. Here, we report the use of label-free and noninvasive microvascular imaging in the hippocampal formation of mice using a 1.7-μm swept-source OCT system. The imaging results demonstrate that the proposed system can visualise blood flow at different locations of the hippocampus corresponding with deep brain areas.
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