Academic literature on the topic 'Nanotechnology - Fluorescent Bioimaging'

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Journal articles on the topic "Nanotechnology - Fluorescent Bioimaging"

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Dunn, Bryce, Marzieh Hanafi, John Hummel, John R. Cressman, Rémi Veneziano, and Parag V. Chitnis. "NIR-II Nanoprobes: A Review of Components-Based Approaches to Next-Generation Bioimaging Probes." Bioengineering 10, no. 8 (August 11, 2023): 954. http://dx.doi.org/10.3390/bioengineering10080954.

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Fluorescence and photoacoustic imaging techniques offer valuable insights into cell- and tissue-level processes. However, these optical imaging modalities are limited by scattering and absorption in tissue, resulting in the low-depth penetration of imaging. Contrast-enhanced imaging in the near-infrared window improves imaging penetration by taking advantage of reduced autofluorescence and scattering effects. Current contrast agents for fluorescence and photoacoustic imaging face several limitations from photostability and targeting specificity, highlighting the need for a novel imaging probe development. This review covers a broad range of near-infrared fluorescent and photoacoustic contrast agents, including organic dyes, polymers, and metallic nanostructures, focusing on their optical properties and applications in cellular and animal imaging. Similarly, we explore encapsulation and functionalization technologies toward building targeted, nanoscale imaging probes. Bioimaging applications such as angiography, tumor imaging, and the tracking of specific cell types are discussed. This review sheds light on recent advancements in fluorescent and photoacoustic nanoprobes in the near-infrared window. It serves as a valuable resource for researchers working in fields of biomedical imaging and nanotechnology, facilitating the development of innovative nanoprobes for improved diagnostic approaches in preclinical healthcare.
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Lunin, Afanasy V., Anna A. Lizunova, Elizaveta N. Mochalova, Maria N. Yakovtseva, Vladimir R. Cherkasov, Maxim P. Nikitin, and Eugene L. Kolychev. "Hematite Nanoparticles from Unexpected Reaction of Ferrihydrite with Concentrated Acids for Biomedical Applications." Molecules 25, no. 8 (April 23, 2020): 1984. http://dx.doi.org/10.3390/molecules25081984.

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The development of synthetic ways to fabricate nanosized materials with a well-defined shape, narrow-sized distribution, and high stability is of great importance to a rapidly developing area of nanotechnology. Here, we report an unusual reaction between amorphous two-line ferrihydrite and concentrated sulfuric or other mineral and organic acids. Instead of the expected dissolution, we observed the formation of new narrow-distributed brick-red nanoparticles (NPs) of hematite. Different acids produce similar nanoparticles according to scanning (SEM) and transmission electron microscopy (TEM), selected area electron diffraction (SAED), X-ray diffraction (XRD), infrared spectroscopy (FTIR), and energy-dispersive X-ray spectroscopy (EDX). The reaction demonstrates new possibilities for the synthesis of acid-resistant iron oxide nanoparticles and shows a novel pathway for the reaction of iron hydroxide with concentrated acids. The biomedical potential of the fabricated nanoparticles is demonstrated by the functionalization of the particles with polymers, fluorescent labels, and antibodies. Three different applications are demonstrated: i) specific targeting of the red blood cells, e.g., for red blood cell (RBC)-hitchhiking; ii) cancer cell targeting in vitro; iii) infrared ex vivo bioimaging. This novel synthesis route may be useful for the development of iron oxide materials for such specificity-demanding applications such as nanosensors, imaging, and therapy.
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Šafranko, Silvija, Dominik Goman, Anamarija Stanković, Martina Medvidović-Kosanović, Tihomir Moslavac, Igor Jerković, and Stela Jokić. "An Overview of the Recent Developments in Carbon Quantum Dots—Promising Nanomaterials for Metal Ion Detection and (Bio)Molecule Sensing." Chemosensors 9, no. 6 (June 11, 2021): 138. http://dx.doi.org/10.3390/chemosensors9060138.

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The fluorescent carbon quantum dots (CQDs) represent an emerging subset of carbonaceous nanomaterials, recently becoming a powerful tool for biosensing, bioimaging, and drug and gene delivery. In general, carbon dots are defined as zero-dimensional (0D), spherical-like nanoparticles with <10 nm in size. Their unique chemical, optical, and electronic properties make CQDs versatile materials for a wide spectrum of applications, mainly for the sensing and biomedical purposes. Due to their good biocompatibility, water solubility, and relatively facile modification, these novel materials have attracted tremendous interest in recent years, which is especially important for nanotechnology and nanoscience expertise. The preparation of the biomass-derived CQDs has attracted growing interest recently due to their low-cost, renewable, and green biomass resources, presenting also the variability of possible modification for the enhancement of CQDs’ properties. This review is primarily focused on the recent developments in carbon dots and their application in the sensing of different chemical species within the last five years. Furthermore, special emphasis has been made regarding the green approaches for obtaining CQDs and nanomaterial characterization toward better understanding the mechanisms of photoluminescent behavior and sensing performance. In addition, some of the challenges and future outlooks in CQDs research have been briefly outlined.
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Singh, Jagtar, Pallavi Nayak, Gurdeep Singh, Madhusmruti Khandai, Rashmi Ranjan Sarangi, and Mihir Kumar Kar. "Carbon Nanostructures as Therapeutic Cargoes: Recent Developments and Challenges." C 9, no. 1 (December 27, 2022): 3. http://dx.doi.org/10.3390/c9010003.

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Recent developments in nanotechnology and process chemistry have expanded the scope of nanostructures to the biomedical field. The ability of nanostructures to precisely deliver drugs to the target site not only reduces the amount of drug needed but also reduces systemic adverse effects. Carbon nanostructures gained traction in pharmaceutical technology in the last decade due to their high stability, ease of synthesis, tunable surface chemistry, and biocompatibility. Fullerene, nanotubes, nanodiamonds, nanodots, and nanoribbons are among the major carbon nanostructures that have been extensively studied for applications in tissue engineering, biosensing, bioimaging, theranostics, drug delivery, and gene therapy. Due to the fluorescent properties of functionalized nanostructures, they have been extensively studied for use as probes in cellular imaging. Moreover, these nanostructures are promising candidates for delivering drugs to the brain, bones, and deep-seated tumors. Still, research gaps need to be addressed regarding the toxicity of these materials in animals as well as humans. This review highlights the physicochemical properties of carbon nanostructures and their categories, methods of synthesis, various techniques for surface functionalization, major biomedical applications, mechanisms involving the cellular uptake of nanostructures, pharmacokinetic considerations, recent patents involving carbon-based nanostructures in the biomedical field, major challenges, and future perspectives.
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Belperain, Sarah, Zi Yae Kang, Andrew Dunphy, Brandon Priebe, Norman H. L. Chiu, and Zhenquan Jia. "Anti-Inflammatory Effect and Cellular Uptake Mechanism of Carbon Nanodots in in Human Microvascular Endothelial Cells." Nanomaterials 11, no. 5 (May 10, 2021): 1247. http://dx.doi.org/10.3390/nano11051247.

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Cardiovascular disease (CVD) has become an increasingly important topic in the field of medical research due to the steadily increasing rates of mortality caused by this disease. With recent advancements in nanotechnology, a push for new, novel treatments for CVD utilizing these new materials has begun. Carbon Nanodots (CNDs), are a new form of nanoparticles that have been coveted due to the green synthesis method, biocompatibility, fluorescent capabilities and potential anti-antioxidant properties. With much research pouring into CNDs being used as bioimaging and drug delivery tools, few studies have been completed on their anti-inflammatory potential, especially in the cardiovascular system. CVD begins initially by endothelial cell inflammation. The cause of this inflammation can come from many sources; one being tumor necrosis factor (TNF-α), which can not only trigger inflammation but prolong its existence by causing a storm of pro-inflammatory cytokines. This study investigated the ability of CNDs to attenuate TNF-α induced inflammation in human microvascular endothelial cells (HMEC-1). Results show that CNDs at non-cytotoxic concentrations reduce the expression of pro-inflammatory genes, mainly Interleukin-8 (IL-8), and interleukin 1 beta (IL-1β). The uptake of CNDs by HMEC-1s was examined. Results from the studies involving channel blockers and endocytosis disruptors suggest that uptake takes place by endocytosis. These findings provide insights on the interaction CNDs and endothelial cells undergoing TNF-α induced cellular inflammation.
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Wang, Peiyuan, Suhua Jiang, Yang Li, Qiang Luo, Jinyan Lin, Lidan Hu, and Lingling Fan. "Corrigendum to “Downshifting nanoprobes with the follicle stimulating hormone peptide fabrication for highly efficient NIR II fluorescent bioimaging guided ovarian tumor surgery” Nanomedicine: Nanotechnology, Biology, and Medicine 28(2020)102198." Nanomedicine: Nanotechnology, Biology and Medicine 40 (February 2022): 102514. http://dx.doi.org/10.1016/j.nano.2021.102514.

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Akram, Zubair, Ali Raza, Muhammad Mehdi, Anam Arshad, Xiling Deng, and Shiguo Sun. "Recent Advancements in Metal and Non-Metal Mixed-Doped Carbon Quantum Dots: Synthesis and Emerging Potential Applications." Nanomaterials 13, no. 16 (August 14, 2023): 2336. http://dx.doi.org/10.3390/nano13162336.

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In nanotechnology, the synthesis of carbon quantum dots (CQDs) by mixed doping with metals and non-metals has emerged as an appealing path of investigation. This review offers comprehensive insights into the synthesis, properties, and emerging applications of mixed-doped CQDs, underlining their potential for revolutionary advancements in chemical sensing, biosensing, bioimaging, and, thereby, contributing to advancements in diagnostics, therapeutics, and the under standing of complex biological processes. This synergistic combination enhances their sensitivity and selectivity towards specific chemical analytes. The resulting CQDs exhibit remarkable fluorescence properties that can be involved in precise chemical sensing applications. These metal-modified CQDs show their ability in the selective and sensitive detection from Hg to Fe and Mn ions. By influencing their exceptional fluorescence properties, they enable precise detection and monitoring of biomolecules, such as uric acid, cholesterol, and many antibiotics. Moreover, when it comes to bioimaging, these doped CQDs show unique behavior towards detecting cell lines. Their ability to emit light across a wide spectrum enables high-resolution imaging with minimal background noise. We uncover their potential in visualizing different cancer cell lines, offering valuable insights into cancer research and diagnostics. In conclusion, the synthesis of mixed-doped CQDs opens the way for revolutionary advancements in chemical sensing, biosensing, and bioimaging. As we investigate deeper into this field, we unlock new possibilities for diagnostics, therapeutics, and understanding complex biological processes.
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Das, Kishan, Neelima Bhatt, Ajith Manayil Parambil, Kajal Kumari, Raj Kumar, Kamla Rawat, Paulraj Rajamani, et al. "Divergent Responses of Hydrophilic CdSe and CdSe@CdS Core–Shell Nanocrystals in Apoptosis and In Vitro Cancer Cell Imaging: A Comparative Analysis." Journal of Functional Biomaterials 14, no. 9 (September 1, 2023): 448. http://dx.doi.org/10.3390/jfb14090448.

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With their distinctive core–shell design, core–shell nanocrystals have drawn interest in catalysis, medicinal research, and nanotechnology. These nanocrystals have a variety of characteristics and possible uses. The application of core–shell nanocrystals offers significant potential in increasing diagnostic and therapeutic approaches for cancer research in apoptosis and in vitro cancer cell imaging. In the present study, we investigated the fluorescence behavior of hydrophilic CdSe (core-only) and CdSe@CdS (core–shell) nanocrystals (NCs) and their potential in cancer cell imaging. The addition of a CdS coating to CdSe NCs increased the fluorescence intensity tenfold. The successful fabrication of core–shell CdSe@CdS nanocrystals was proven by a larger particle size (evaluated via DLS and TEM) and their XRD pattern and surface morphology compared to CdSe (core-only) NCs. When these NCs were used for bioimaging in MCF-7 and HEK-293 cell lines, they demonstrated excellent cellular uptake due to higher fluorescence intensity within cancerous cells than normal cells. Comparative cytotoxicity studies revealed that CdSe NCs were more toxic to all three cell lines (HEK-293, MCF-7, and HeLa) than CdSe@CdS core–shell structures. Furthermore, a decrease in mitochondrial membrane potential and intracellular ROS production supported NCs inducing oxidative stress, which led to apoptosis via the mitochondria-mediated pathway. Increased cytochrome c levels, regulation of pro-apoptotic gene expression (e.g., p53, Bax), and down-regulation of Bcl-2 all suggested cellular apoptosis occurred via the intrinsic pathway. Significantly, at an equivalent dose of core–shell NCs, core-only NCs induced more oxidative stress, resulting in increased apoptosis. These findings shed light on the role of a CdS surface coating in reducing free radical release, decreasing cytotoxicity, and improving fluorescence, advancing the field of cell imaging.
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Mansuriya, Bhargav D., and Zeynep Altintas. "Carbon Dots: Classification, Properties, Synthesis, Characterization, and Applications in Health Care—An Updated Review (2018–2021)." Nanomaterials 11, no. 10 (September 27, 2021): 2525. http://dx.doi.org/10.3390/nano11102525.

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Carbon dots (CDs) are usually smaller than 10 nm in size, and are meticulously formulated and recently introduced nanomaterials, among the other types of carbon-based nanomaterials. They have gained significant attention and an incredible interest in the field of nanotechnology and biomedical science, which is merely due to their considerable and exclusive attributes; including their enhanced electron transferability, photobleaching and photo-blinking effects, high photoluminescent quantum yield, fluorescence property, resistance to photo-decomposition, increased electrocatalytic activity, good aqueous solubility, excellent biocompatibility, long-term chemical stability, cost-effectiveness, negligible toxicity, and acquaintance of large effective surface area-to-volume ratio. CDs can be readily functionalized owing to the abundant functional groups on their surfaces, and they also exhibit remarkable sensing features such as specific, selective, and multiplex detectability. In addition, the physico-chemical characteristics of CDs can be easily tunable based on their intended usage or application. In this comprehensive review article, we mainly discuss the classification of CDs, their ideal properties, their general synthesis approaches, and primary characterization techniques. More importantly, we update the readers about the recent trends of CDs in health care applications (viz., their substantial and prominent role in the area of electrochemical and optical biosensing, bioimaging, drug/gene delivery, as well as in photodynamic/photothermal therapy).
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Jing, Hong Hui, Fevzi Bardakci, Sinan Akgöl, Kevser Kusat, Mohd Adnan, Mohammad Jahoor Alam, Reena Gupta, et al. "Green Carbon Dots: Synthesis, Characterization, Properties and Biomedical Applications." Journal of Functional Biomaterials 14, no. 1 (January 2, 2023): 27. http://dx.doi.org/10.3390/jfb14010027.

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Carbon dots (CDs) are a new category of crystalline, quasi-spherical fluorescence, “zero-dimensional” carbon nanomaterials with a spatial size between 1 nm to 10 nm and have gained widespread attention in recent years. Green CDs are carbon dots synthesised from renewable biomass such as agro-waste, plants or medicinal plants and other organic biomaterials. Plant-mediated synthesis of CDs is a green chemistry approach that connects nanotechnology with the green synthesis of CDs. Notably, CDs made with green technology are economical and far superior to those manufactured with physicochemical methods due to their exclusive benefits, such as being affordable, having high stability, having a simple protocol, and being safer and eco-benign. Green CDs can be synthesized by using ultrasonic strategy, chemical oxidation, carbonization, solvothermal and hydrothermal processes, and microwave irradiation using various plant-based organic resources. CDs made by green technology have diverse applications in biomedical fields such as bioimaging, biosensing and nanomedicine, which are ascribed to their unique properties, including excellent luminescence effect, strong stability and good biocompatibility. This review mainly focuses on green CDs synthesis, characterization techniques, beneficial properties of plant resource-based green CDs and their biomedical applications. This review article also looks at the research gaps and future research directions for the continuous deepening of the exploration of green CDs.
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Dissertations / Theses on the topic "Nanotechnology - Fluorescent Bioimaging"

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Gortari, Antu Nehuen. "Metasurfaces for bioimaging." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS416/document.

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Au cours des dernières années, des efforts importants ont été déployés pour développer des métasurfaces (MSs) électromagnétiques avec la possibilité de changer de manière abrupte les propriétés de la lumière. Ces avancées ont ouvert une nouvelle gamme de possibilités pour contrôler la lumière en utilisant des dispositifs optiques ultra-minces. Dans ce contexte, et plus spécifiquement dans le spectre visible, les applications en bio-imagerie s’avèrent particulièrement intéressantes. Une technique qui est particulièrement bien adaptée à l'étude de molécules proches d'une membrane cellulaire est la microscopie à fluorescence par réflexion interne (TIRFM), qui repose sur un champ évanescent d'excitation. Dans ce cas la lumière incidente est totalement réfléchie sur une interphase (typiquement verre/eau) en raison de son angle d'incidence élevé. À ce jour, la TIRFM est généralement mise en œuvre à l'aide d'objectifs volumineux de grande ouverture numérique et de petit champ de vision.Dans ce travail de thèse, nous réalisons de substrats pour la microscopie TIRF à base de métasurfaces constituées de réseaux périodiques de structures asymétriques fabriquées en dioxyde de titane (TiO2) sur du verre borosilicaté. Ces structures, aussi petites que 48 nm, ont été optimisées à l’aide de simulations numériques "Rigorous coupled-wave analysis” (RCWA) dans le but de coupler de 50 à 90% de la lumière incidente dans le premier ordre de diffraction avec des angles élevés (θ > 63deg). Le fait de pouvoir utiliser des objectifs de faible grossissement et d'avoir une grande zone de champ évanescent fournit des conditions TIRF uniques qui ne sont pas accessibles par les méthodes traditionnelles. De plus, ces structures sont compatibles avec la lithographie par nanoimpression UV, ce qui permet d’envisager une fabrication à bas coût et à grande échelle. Outre la conception, et la fabrication, dans cette thèse nous aboutissons à une preuve de principe de la microscopie TIRF basée sur des métasurfaces en milieu biologique en imageant notamment des membranes fluorescentes de cellules souches. Ces métasurfaces permettent ainsi l’implémentation TIRFM à contraste élevé et à faible photo-blanchissement compatible avec des microscopes à champ large peu coûteux
In recent years there has been a significant effort to push electromagnetic metasurfaces with the ability to abruptly change light properties into visible wavelengths. These advancements have opened a new range of possibilities to reshape light using ultra-thin optical devices and there is one field that is starting to gather attention: bioimaging. One technique particularly well suited for the study of molecules near a cell membrane is Total Internal Reflection Fluorescence (TIRF) microscopy, which relies on an evanescence field created by light being totally internally reflected within a glass substrate due to its high incidence angle. As of today, TIRF is generally implemented using bulky high-NA, small field of view oil objectives.In this project we present the realization of metasurface-based TIRF microscopy substrates consisting of periodic 2D arrays of asymmetric structures fabricated in titanium dioxide on borosilicate glass. These patterns, as small as 48nm, were optimized through rigorous coupled-wave analysis to couple 50-90% of the incoming normally incident light into the first diffraction order, which outputs at an angle that suffices total internal reflection in water and eliminates the requirement for high NA objectives or prisms to achieve TIRF. Being able to utilize lower-magnification air objectives and having a large evanescence field area provide unique TIRF conditions not accessible by traditional methods. Additionally, these structures are compatible with soft UV nanoimprint lithography, for cost-effective scale production, to give TIRF’s high contrast, low photodamage and low photobleaching capabilities to inexpensive wide-field microscopes
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Grimes, Logan. "DEVELOPENT OF A PHOSPHOLIPID ENCAPSULATION PROCESS FOR QUANTUM DOTS TO BE USED IN BIOLOGIC APPLICATIONS." DigitalCommons@CalPoly, 2014. https://digitalcommons.calpoly.edu/theses/1237.

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The American Cancer Society predicts that 1,665,540 people will be diagnosed with cancer, and 585,720 people will die from cancer in 2014. One of the most common types of cancer in the United States is skin cancer. Melanoma alone is predicted to account for 10,000 of the cancer related deaths in 2014. As a highly mobile and aggressive form of cancer, melanoma is difficult to fight once it has metastasized through the body. Early detection in such varieties of cancer is critical in improving survival rates in afflicted patients. Present methods of detection rely on visual examination of suspicious regions of tissue via various forms of biopsies. Accurate assessment of cancerous cells via this method are subjective, and often unreliable in the early stages of cancer formation when only few cancer cells are forming. With fewer cancer cells, it is less likely that a cancer cell will appear in a biopsied tissue. This leads to a lower detection rate, even when cancer is present. This lack of detection when cancer is in fact present is referred to as a false negative. False negatives can have a highly detrimental effect on treating the cancer as soon as possible. More accurate methods of detecting cancer in early stages, in a nonsubjective form would alleviate these problems. A proposed alternative to visual examination of biopsied legions is to utilize fluorescent nanocrystalline biomarker constructs to directly attach to the abnormal markers found on cancerous tissues. Quantum dots (QDs) are hydrophobic nanoscale crystals composed of semiconducting materials which fluoresce when exposed to specific wavelengths of radiation, most commonly in the form of an ultraviolet light source. The QD constructs generated were composed of cadmium-selenium (CdSe) cores encapsulated with zinc-sulfide (ZnS) shells. These QDs were then encapsulated with phospholipids in an effort to create a hydrophilic particle which could interact with polar fluids as found within the human body. The goal of this thesis is to develop a method for the solubilization, encapsulation, and initial functionalization of CdSe/ZnS QDs. The first stage of this thesis focused on the generation of CdSe/ZnS QDs and the fluorescence differences between unshelled and shelled QDs. The second stage focused on utilizing the shelled QDs to generate hydrophilic constructs by utilizing phospholipids to bind with the QDs. Analysis via spectroscopy was performed in an effort to characterize the difference in QDs both prior to and after the encapsulation process. The method generated provides insight on fluorescence trends and the encapsulation of QDs in polar substances. Future research focusing on the repeatability of the process, introducing the QD constructs to a biological material, and eventual interaction with cancer cells are the next steps in generating a new technique to target and reveal skin cancer cells in the earliest possible stages without using a biopsy.
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Huisman, Maximiliaan. "Vision Beyond Optics: Standardization, Evaluation and Innovation for Fluorescence Microscopy in Life Sciences." eScholarship@UMMS, 2019. https://escholarship.umassmed.edu/gsbs_diss/1017.

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Fluorescence microscopy is an essential tool in biomedical sciences that allows specific molecules to be visualized in the complex and crowded environment of cells. The continuous introduction of new imaging techniques makes microscopes more powerful and versatile, but there is more than meets the eye. In addition to develop- ing new methods, we can work towards getting the most out of existing data and technologies. By harnessing unused potential, this work aims to increase the richness, reliability, and power of fluorescence microscopy data in three key ways: through standardization, evaluation and innovation. A universal standard makes it easier to assess, compare and analyze imaging data – from the level of a single laboratory to the broader life sciences community. We propose a data-standard for fluorescence microscopy that can increase the confidence in experimental results, facilitate the exchange of data, and maximize compatibility with current and future data analysis techniques. Cutting-edge imaging technologies often rely on sophisticated hardware and multi-layered algorithms for reconstruction and analysis. Consequently, the trustworthiness of new methods can be difficult to assess. To evaluate the reliability and limitations of complex methods, quantitative analyses – such as the one present here for the 3D SPEED method – are paramount. The limited resolution of optical microscopes prevents direct observation of macro- molecules like DNA and RNA. We present a multi-color, achromatic, cryogenic fluorescence microscope that has the potential to produce multi-color images with sub-nanometer precision. This innovation would move fluorescence imaging beyond the limitations of optics and into the world of molecular resolution.
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Book chapters on the topic "Nanotechnology - Fluorescent Bioimaging"

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Wang, Lei, and Guo-Bin Qi. "Supramolecular Self-assembled Nanomaterials for Fluorescence Bioimaging." In In Vivo Self-Assembly Nanotechnology for Biomedical Applications, 1–29. Singapore: Springer Singapore, 2018. http://dx.doi.org/10.1007/978-981-10-6913-0_1.

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Bhamore, Jigna R., Tae-Jung Park, and Suresh Kumar Kailasa. "Ultrasmall fluorescent nanomaterials for sensing and bioimaging applications." In Sustainable Nanotechnology for Environmental Remediation, 531–70. Elsevier, 2022. http://dx.doi.org/10.1016/b978-0-12-824547-7.00003-5.

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Conference papers on the topic "Nanotechnology - Fluorescent Bioimaging"

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Deng, Wei, Krystyna Drozdowicz-Tomsia, Dayong Jin, and Ewa M. Goldys. "Silver nanostructure coated beads enhance fluorescence for sensitive immunoassays and bioimaging." In 2010 International Conference on Nanoscience and Nanotechnology (ICONN). IEEE, 2010. http://dx.doi.org/10.1109/iconn.2010.6045197.

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