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This PDF file contains the front matter associated with SPIE Proceedings Volume 11976, including the Title Page, Copyright information, and Table of Contents.
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Nanoscale Imaging, Sensing, and Actuation for Biomedical Applications I
The use of enhanced electromagnetic fields in nanophotonic structures is moving from plasmonic to all-dielectric platforms in order to overcome the intrinsic Ohmic losses from metal inclusions. In this work, we demonstrate that strong electromagnetic fields may be generated in the infrared without heating the nearby molecules by exciting anapole modes in a slotted all-dielectric cylinder on a glass substrate surrounded by water. Numerical calculations are used to prove that the platform is useful to manipulate small biomolecules without heating.
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Beyond structured illumination microscopy (SIM) which uses diffraction-limited light illumination, specially designed nanostructures such as metallic nanoantenna arrays generating localized surface plasmon have been developed to expand the frequency information without increasing photon energy. In this study, disordered temperature-annealed nanocomposite islands were used to create random distribution of nanospeckles because nanoisland substrates can be mass-produced in a large observation area by thin film deposition and annealing process. In our nanospeckle illumination microscopy (NanoSIM) system, azimuthal scanning illumination (ASI) on nanoislands creates a randomly localized nearfield distribution that induces an arbitrary number of fluorescence images. By the difficulty of obtaining structured illumination patterns of random nanostructures, images were reconstructed using a modified blind-SIM algorithm which fits well with the ASI system. A 100 nm fluorescent nanobead experiment confirms that NanoSIM provides resolution enhancement of spatial information in good agreement with the results obtained from AFM images. We emphasize that using random nanospeckles of disordered nanocomposite islands can provide highly accessible super-resolution. The results can be applied to imaging and sensing techniques, such as switching-based multi-channel microscopy.
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We experimentally demonstrate ghost imaging in the frequency domain based on a speckle pattern as a reference. Our scheme can measure spectrum with high resolution. We perform the spectral measurement by a time stretch system that maps from frequency to time. We achieve a reconstruction of our signal by analyzing the output spectrum while shifting the speckle field.
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Imaging inside a turbid media is range limited. In contrast, sensing the medium’s optical properties is possible in larger depths using the iterative multi-plane optical properties extraction (IMOPE) technique. It analyzes the reemitted light phase image reconstructed from the iterative multi-plane Gerchberg-Saxton (GS) algorithm. The root mean square (RMS) of the phase yields two graphs with opposite behaviors, that cross each other in μ's,cp. The graphs enable the extraction of the reduced scattering coefficient, μs', of the measured tissue. The IMOPE was originally developed for illumination of red wavelength and for biological applications and was extended to the blue regime of the electromagnetic field, which is applicable for underwater research. In this work, we aim to extend the range of μs' detection by optical magnification. We use a modified diffusion theory and show how μ's,cp shifts with the varying magnification. The theoretical results were then tested experimentally, using agar-based phantoms with varying scatterings coefficients.
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Nanoscale Imaging, Sensing, and Actuation for Biomedical Applications IV
Isoflurane, sevoflurane, and desflurane have been shown to have different neurotoxic effects. However, the underlying mechanism at the single molecular level remains unknown. Isoflurane, sevoflurane, and desflurane can differently induce mitochondrial dysfunction and ATP synthase is the critical component of mitochondrial function. We, therefore, set out to assess whether different anesthetics can selectively impair the interaction of ADP and ATP synthase at a single molecular level. We also employed Nano needle platform measured Tau at threonine 217 (Tau-PT217) and 181 (Tau-PT181) as newly identified blood biomarkers of Alzheimer’s disease (AD).
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In today’s research area it is extremely important to assemble nanomaterials into electric devices at the nanoscale level due to the rapid expansion of nanotechnology in various fields. Designing a nanohybrid composed of gold nanoparticles (AuNPs) and red-emitting carbon dots (CDs) can be used to develop a fluorescence lifetime imaging (FLIM) based logic gate that can respond to multiple input parameters. The AuNPs are conjugated to CDs surfaces through a strong covalent linkage between them. These fluorescence lifetimes-based logic gates could be the new way to overcome the limitation of fluorescence intensity-based logic gates. The Au-CDs nanohybrid shows significant fluorescence quenching of pristine CDs after conjugation of gold nanoparticles. This quenched fluorescence can be recovered back by using a proper recovering agent giving us a reversible logic output. This nanohybrid can be used to construct complex logic functions as the fluorescence logic output is independent of concentration and excitation source.
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The hybrid metal/quantum dots (QDs) structures were synthesized and characterized with different thicknesses of silica shells by uncomplicated and typical methods. By engineering the shell thickness and Au nanoparticles (Au NPs) core size with shapes, the interaction between Au NPs and QDs could be adjusted flexibly to witness the energy transfer process thoroughly. The improvement of the emission intensity and the reduction in the PL lifetime with the appropriate thickness of silica layer were obtained. Likewise, the energy transfer efficiency between QDs donor-acceptor pairs was inferred as the dominance of larger QDs with hybrid structures. The quenching of QDs donors and the enhancement of QDs acceptors in PL emission intensity were determined by the different core-shell structures. Finally, as-prepared metal/silica/QDs structures have been explored for bio-imaging applications, leading to enhanced light absorption and sensitivity.
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We performed a Monte Carlo simulation to detect the tattoo ink location in the dermis layer of the human skin. Tattoo ink (thickness of 0.2mm) was located between the upper dermis layer (thickness of 2mm) and the lower dermis layer (thickness of 8mm). An appreciable difference in the spatially resolved diffuse reflectance (DR) intensity was found between the skin without tattoo and the tattooed skin. The point at which the skin without tattoo and the tattooed skin DR intensity profile intersect is called the crossover point (Cp). The slopes were extracted from the DR intensity profile before and after the Cp for a wavelength range from 400-1,000nm. The slopes are extracted from each wavelength, and we plotted the calculated square slopes versus wavelength. In the shorter wavelengths region (400-500nm), two-layer (2L) behavior was observed, and in the longer wavelengths region (600-1,000nm), a single layer behavior was observed. This confirms the tattoo ink was located at the dermis layer, and the longer wavelengths penetrate the deeper tissue. This Cp can be used to assess ink depth in order to remove the tattoo ink completely without damage to the surrounding skin.
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Deep tissue imaging using visible light is challenging due to its turbid nature. Nevertheless, clinical information can be detected by sensing changes in the tissue’s optical properties with low spatial resolution. The most challenging aspect is the spectral dependent scattering, which varies with physiological state and tissue layer. In this paper, we present the multi-layer study of the reflection-based iterative multiplane optical property extraction (IMOPE) technique. The IMOPE is a noninvasive nanophotonics technique that detects medium scattering properties based on the reemitted light phase. The extracted scattering properties are used as indicators of the internal tissue information and the presence of additional nanoparticles (NPs) in it. The technique is a combination of a theoretical model, an experimental setup, and the phase retrieval Gerchberg-Saxton algorithm. The IMOPE experimental setup records light intensity images at different locations, in order to reconstruct the phase by the multi-plane GS algorithm. Once the phase distribution is reconstructed, its root mean square (RMS) is calculated and compared to a theoretical model for obtaining the reduced scattering coefficient. This work presents the study of single-layer and two-layer tissue-like phantoms and a new phase image analysis that provides detection of different scattering layers with 0.2mm-1 sensitivity at different depths, following layers up to 6mm thickness. The IMOPE with the new phase image analysis was applied for the detection of the novel iron-based NPs drug (Nano-Leish-IL) in mice leishmaniasis lesions, where it was detected in the epidermis (∼13μm) and dermis (∼160μm) at different stages of the disease.
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Liposomes are a promising drug delivery system, owing to their biocompatibility and ability to efficiently encapsulate and protect a wide range of molecules for medical applications. Active targeting of the liposomes is typically performed by surface modification, which enables delivery of the liposomes to a specific target tissue. Tumor cells are characterized by high glucose demand and high metabolic activity, because of the increased requirement of energy to feed uncontrolled proliferation. Taking advantage of the increased glucose uptake by cancer cells, we developed a glucose-labeled liposome, which is tumor-targeted - both by recognition of over-expressed glucose transporters on tumor cells, and by the unique characteristics of tumor vasculature that allow greater accumulation of nanoparticles. In this study, glucosecoated liposome uptake was evaluated in different types of cancer cells, both quantitatively and qualitatively. We found that liposomes with glucose coating were preferentially uptaken by cancer cell lines with high metabolic activity, compared to liposomes without glucose coating. Moreover, cell lines with high metabolic activity exhibited higher uptake of liposomes with glucose coating, as compared to cell lines with low metabolic activity and to non-cancerous cell lines.
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Gold nanoparticles (GNPs) are becoming an increasingly prominent biomedical tool. GNPs are biocompatible and can carry high payloads and a wide array of biological materials, making them an ideal delivery vector for various therapeutics, such as gene therapy. However, one major obstacle to clinical application is endosomal entrapment and subsequent degradation of the nanoparticletherapy complex. Coating GNPs with an endosomal escape agent can serve as an effective approach to overcome this challenge. This study explores the probability of different types of coated GNPs to perform endosomal escape. We used a novel, multi-modal approach applying fluorescent confocal microscopy, as well as sophisticated image analysis, to provide a quantitative and uniform method that can denote endosomal escape efficacy. Our findings can ultimately advance understanding of endosomal escape abilities of various GNP coatings and promote their application for gene therapy.
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Delivery of therapeutics to tumors is a major challenge, due to the sequence of formidable biological barriers in the body and tumor, which limit the penetration of various nano-carriers and drugs into the tumor. Exosomes are promising vectors for delivery of anti-tumor therapies, due to their biocompatibility, ability to evade clearance, and innate ability to home to, and interact with, target cells. However, promoting clinical application of exosome-based therapeutics requires elucidation of key issues, including exosome bio-distribution, tumor targeting, and the ability to overcome tumor barriers. Here, we examined these parameters using mesenchymal stem cell (MSCs)-derived exosomes loaded with gold nanoparticles (GNPs), aiming to delineate design principles for therapy loading and delivery. This novel technology provides essential and fundamental knowledge on exosomes for enhanced targeted drug delivery to tumors, and has potential to promote clinical translation of exosome-based cancer therapy.
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