122 research outputs found
Developing Near-infrared Emitting DNA-stabilized Silver Nanoclusters for Biomedical Imaging
No full textAdvancements in bioimaging modalities have changed the face of modern medicine. However, current techniques such as MRI and CT utilize hazardous radiation, contrast agents with toxic effects, and possess with limited resolution for deep tissue imaging on length scales relevant for cellular processes. In vivo fluorescence imaging in the near-infrared (NIR) window (750-1700 nm) is an emerging deep tissue imaging technique that offers the possibility of achieving micron-scale spatial resolutions for clearer images of anatomical structures in real time. This thesis develops NIR-emissive DNA-stabilized silver nanoclusters (AgN-DNAs) as fluorophores for non-hazardous fluorescence imaging. We focused on studying the chemical and photophysical properties of AgN-DNAs emitting in NIR I (650-950 nm) wavelengths. First, we worked towards tuning the synthesis conditions to optimize the chemical yields of these nanoclusters, purifying monodisperse and single-emissive species in solution, and determining their chemical compositions. Additionally, we tested the stability of NIR-emissive AgN-DNAs in physiological conditions and aimed to protect these nanoclusters against degradation to evaluate their applicability for fluorescence imaging. We found that the post-reduction temperature used for the nanoclusters after synthesis can significantly increase the brightness of known NIR-emissive AgN-DNAs and decrease the time it takes to achieve maximum emission intensity. Also, new AgN-DNAs were found to evolve from red emissive AgN-DNAs upon changing post-reduction conditions. Mass-spectra of HPLC-purified NIR-emissive AgN-DNAs indicate that these nanoclusters are stabilized by 2 DNA strands, containing six neutral silver atoms and, in some cases, chloride ligands. Attempts to use polyamines to stabilize the AgN-DNAs in saline conditions did not aid in protecting them from emission quenching, but instead, some nanoclusters were found to be stable on their own without modification. Lastly, preliminary in vivo experiments utilized a promising NIR-emissive AgN-DNA in a mouse model, which displayed bright luminescence for several hours while indicating no overt signs of toxicity to the mouse’s liver or spleen. This work laid the groundwork for improved fundamental understanding of methods to discover new NIR-emissive AgN-DNAs, optimize their chemical yields, and establish them as suitable and safe fluorophores for bioimaging techniques
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Understanding Structure-Property Relationships of DNA-Stabilized Silver Nanoclusters with Near-Infrared Emission
No full textAgN-DNAs lie at the unique intersection of metal cluster science and DNA nanotechnology, combining the atomic precision of ligand-stabilized metal clusters with the sequence programmability of DNA nanomaterials. By varying the nucleobase composition, it is possible to fine-tune their composition and geometry, and thereby tune their photophysical properties. These capabilities make AgN-DNAs promising candidates as tunable emitters for applications in biological imaging, benefiting from their small molecular-like size, bright emission, low toxicity, and cost-effective synthesis. AgN-DNAs are known for their rod-like nanocluster geometries and nanosecond-lived fluorescence. One of the most exciting prospects for AgN-DNAs is their potential for emission in the second near-infrared (NIR-II) region, which is crucial for deep tissue imaging due to its ability to penetrate tissue for several centimeters. With the aim to fully realize the potential of AgN-DNAs for NIR-II imaging, it is essential to develop a deeper understanding of how their structure relates to their optical properties so that NIR-II-emitting AgN-DNAs can be effectively designed.Recent breakthroughs in AgN-DNA structure and composition revealed important correlations between nanocluster structure and photophysical behavior. These insights have been made possible by advances in mass spectrometry and crystallography of pure AgN-DNAs, in combination with high-throughput experiments and machine learning algorithms to design AgN- DNAs with targeted properties. This approach has been particularly useful given the challenges of growing AgN-DNA crystals that are suitable for diffraction studies and the complexity of determining precise molecular formulas via mass spectrometry, as traditional methods alone are insufficient for exploring the vast sequence space of DNA templates that could guide the creation of novel AgN-DNAs.
This dissertation discusses groundbreaking discoveries in AgN-DNA structure, ligand composition and photophysical properties that have been enabled by high throughput synthesis and fluorimetry together with detailed analytical studies of purified AgN-DNAs. We unveil the first known AgN-DNAs that contain eight valence electrons and exhibit only microsecond-lived luminescence, making them the first reported DNA-stabilized luminescent quasi-spherical superatoms. Our discovery of a new class of chloride-stabilized AgN-DNAs enabled the first ab initio calculations of AgN-DNA electronic structure and introduced promising strategies to stabilize these emitters in biologically relevant conditions. Finally, we reported dual-emissive AgN-DNAs with fluorescence in the NIR-I spectral window and microsecond-lived photoluminescence in the NIR-II spectral window, opening the door to the tissue transparency window for effective fluorescence imaging in the NIR-II range
Initial Impact of the Gabíkovo Hydroelectric Scheme on the Species Richness and Composition of 0+ Fish Assemblages in the Slovak Flood Plain, River Danube
No full textRelatively little information exists on the effects of hydroelectric schemes on 0+ fish composition in large European rivers because few or no pre-impact data exist. We compared 0+ fish species richness and composition, relative density, fish size as well as available and used habitat using data from 12 floodplain sites sampled just prior to (1992) and four years after (1996) the start of operations of the Gabíkovo hydropower station on the River Danube (Slovakia). We also used modelling techniques to assess the change in species richness and habitat use and to predict 1996 occurrences from the 1992 data set. The floodplain was greatly modified by the hydroscheme. Only 12 of 27 sites sampled in August 1992 were extant in August 1996. Therefore, all four channel types identified (flowing, abandoned, weir, wing-dam) were more lentic in 1996 than in 1992, with increased width, smaller-sized sediment (silt, clay) and greater amounts of macrophytes. After the operations of the hydroscheme, the overall relative density of fishes (individuals per surface area) of all ages decreased, with the exception of 0+ fishes, despite a slight reduction in 0+ fish density in all channel types except weirs. Species number increased from 25 to 28, although in all channel types there was a change in the composition of the 0+ fish assemblages, with rheophiles generally replaced by limnophiles and migrants from the lower Danube. The two most important microhabitat variables were the proportion of macrophytes and gravel, the latter being the factor distinguishing 0+ fish microhabitat use in 1992 (preferences) and 1996 (indifference or avoidance). Species richness and 0+ fish density in 1996 could be predicted from the 1992 data using simple log-linear models (density, richness, sample number). Species-specific occurrence in 1996 could not be predicted using environmental/fish data from 1992 with multiple regression or generalized additive models (GAM). However, the overall GAM from 1992 could predict overall fish occurrence in 1996
Beyond nature's base pairs: machine learning-enabled design of DNA-stabilized silver nanoclusters
No full textSequence-encoded biomolecules such as DNA and peptides are powerful programmable building blocks for nanomaterials. This paradigm is enabled by decades of prior research into how nucleic acid and amino acid sequences dictate biomolecular interactions. The properties of biomolecular materials can be significantly expanded with non-natural interactions, including metal ion coordination of nucleic acids and amino acids. However, these approaches present design challenges because it is often not well-understood how biomolecular sequence dictates such non-natural interactions. This Feature Article presents a case study in overcoming challenges in biomolecular materials with emerging approaches in data mining and machine learning for chemical design. We review progress in this area for a specific class of DNA-templated metal nanomaterials with complex sequence-to-property relationships: DNA-stabilized silver nanoclusters (AgN-DNAs) with bright, sequence-tuned fluorescence colors and promise for biophotonics applications. A brief overview of machine learning concepts is presented, and high-throughput experimental synthesis and characterization of AgN-DNAs are discussed. Then, recent progress in machine learning-guided design of DNA sequences that select for specific AgN-DNA fluorescence properties is reviewed. We conclude with emerging opportunities in machine learning-guided design and discovery of AgN-DNAs and other sequence-encoded biomolecular nanomaterials
Female leaders in commercial real estate : to the women following in their footsteps
No full textThesis (S.M.)--Massachusetts Institute of Technology, Program in Real Estate Development in Conjunction with the Center for Real Estate, 2009.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student submitted PDF version of thesis.Includes bibliographical references (p. 71-73).Within commercial real estate, women are not as likely as men to achieve senior-level executive positions. Commercial real estate has been slow to change in terms of achieving gender parity, and though improvements have been made in the status of women in leadership positions, gender-based disparity still exists. The purpose of this study is to shed more light on the facilitators and barriers to career advancement of women in commercial real estate who have achieved top-level leadership positions. Thirteen women holding senior-level management positions in the commercial real estate industry were interviewed regarding facilitators to career advancement and notable barriers, the role of mentors, and work-life balance issues. What route did these women take to the top and what did they encounter along the way? Each story told involved some combination of diligent work, the pursuit of opportunities, and the will to succeed. The results from this study supported much of the research that has been done on this topic. Gender barriers, biases, and stereotypes were met along the way, but these women succeeded in spite of these barriers. The women attribute their success to facilitators of career advancement such as a strong work ethic, relationship building and risk-taking. While this thesis shed light on the careers of women in commercial real estate, it also raises at least two questions. How similar are the career paths of women and men in commercial real estate in terms of facilitators and barriers to advancement? Does the glass ceiling appear thin or non-existent once female executives are above it?by Jodie Copp Poirier.S.M
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Optical Materials with a Genome: Nanophotonics with DNA-Stabilized Silver Clusters
No full textFluorescent silver clusters with unique rod-like geometries are stabilized by DNA. The sizes and colors of these clusters, or AgN-DNA, are selected by DNA base sequence, which can tune peak emission from blue-green into the near-infrared. Combined with DNA nanostructures, AgN-DNA promise exciting applications in nanophotonics and sensing. Until recently, however, a lack of understanding of the mechanisms controlling AgN-DNA fluorescence has challenged such applications. This dissertation discusses progress toward understanding the role of DNA as a "genome" for silver clusters and toward using DNA to achieve atomic-scale precision of silver cluster size and nanometer-scale precision of silver cluster position on a DNA breadboard. We also investigate sensitivity of AgN-DNA to local solvent environment, with an eye toward applications in chemical and biochemical sensing. Using robotic techniques to generate large data sets, we show that fluorescent silver clusters are templated by certain DNA base motifs that select "magic-sized" cluster cores of enhanced stabilities. The linear arrangement of bases on the phosphate backbone imposes a unique rod-like geometry on the clusters. Harnessing machine learning and bioinformatics techniques, we also demonstrate that sequences of DNA templates can be selected to stabilize silver clusters with desired optical properties, including high fluorescence intensity and specific fluorescence wavelengths, with much higher rates of success as compared to current strategies.The discovered base motifs can be also used to design modular DNA host strands that enable individual silver clusters with atomically precise sizes to bind at specific programmed locations on a DNA nanostructure. We show that DNA-mediated nanoscale arrangement enables near-field coupling of distinct clusters, demonstrated by dual-color cluster assemblies exhibiting resonant energy transfer. These results demonstrate a new degree of control over the optical properties and relative positions of nanoparticles, selected almost solely by the sequence of DNA.AgN-DNA are promising chemical and biochemical sensors due to the sensitivity of their fluorescence to local environment. However, the mechanisms behind many sensing schemes are not understood, and the nature of the excited state of the silver cluster itself remains unknown. To probe the fluorescence mechanisms of AgN-DNA, we investigate the behavior of purified solutions of these clusters in various solvents. We find that standard models for fluorophore solvatochromism, including the Lippert-Mataga model, do not describe AgN-DNA fluorescence because such models neglect specific interactions between the cluster and surrounding solvent molecules. Fluorescence colors are well-modeled by Mie-Gans theory, suggesting that the local dielectric environment of the cluster does play a role in fluorescence, although additional specific solvent interactions and cluster shape changes may also determine fluorescence color and intensity. These results suggest that AgN-DNA may be sensitive to changes in local dielectric environment on nanometer length scales and may also act as sensors for small molecules with affinity for DNA
DNA-Protected Silver Clusters for Nanophotonics
No full textDNA-protected silver clusters (AgN-DNA) possess unique fluorescence properties that depend on the specific DNA template that stabilizes the cluster. They exhibit peak emission wavelengths that range across the visible and near-IR spectrum. This wide color palette, combined with low toxicity, high fluorescence quantum yields of some clusters, low synthesis costs, small cluster sizes and compatibility with DNA are enabling many applications that employ AgN-DNA. Here we review what is known about the underlying composition and structure of AgN-DNA, and how these relate to the optical properties of these fascinating, hybrid biomolecule-metal cluster nanomaterials. We place AgN-DNA in the general context of ligand-stabilized metal clusters and compare their properties to those of other noble metal clusters stabilized by small molecule ligands. The methods used to isolate pure AgN-DNA for analysis of composition and for studies of solution and single-emitter optical properties are discussed. We give a brief overview of structurally sensitive chiroptical studies, both theoretical and experimental, and review experiments on bringing silver clusters of distinct size and color into nanoscale DNA assemblies. Progress towards using DNA scaffolds to assemble multi-cluster arrays is also reviewed
Beyond nature's base pairs: machine learning-enabled design of DNA-stabilized silver nanoclusters
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An Atom-Precise Understanding of DNA-Stabilized Silver Nanoclusters
No full textConspectusDNA-stabilized silver nanoclusters (AgN-DNAs) are sequence-encoded fluorophores. Like other noble metal nanoclusters, the optical properties of AgN-DNAs are dictated by their atomically precise sizes and shapes. What makes AgN-DNAs unique is that nanocluster size and shape are controlled by nucleobase sequence of the templating DNA oligomer. By choice of DNA sequence, it is possible to synthesize a wide range of AgN-DNAs with diverse emission colors and other intriguing photophysical properties. AgN-DNAs hold significant potential as "programmable" emitters for biological imaging due to their combination of small molecular-like sizes, bright and sequence-tuned fluorescence, low toxicities, and cost-effective synthesis. In particular, the potential to extend AgN-DNAs into the second near-infrared region (NIR-II) is promising for deep tissue imaging, which is a major area of interest for advancing biomedical imaging. Achieving this goal requires a deep understanding of the structure-property relationships that govern AgN-DNAs in order to design AgN-DNA emitters with sizes and geometries that support NIR-II emission.In recent years, major advances have been made in understanding the structure and composition of AgN-DNAs, enabling new insights into the correlation of nanocluster structure and photophysical properties. These advances have hinged on combined innovations in mass characterization and crystallography of compositionally pure AgN-DNAs, together with combinatorial experiments and machine learning-guided design. A combined approach is essential due to the major challenge of growing suitable AgN-DNA crystals for diffraction and to the labor-intensive nature of preparing and solving the molecular formulas of atomically precise AgN-DNAs by mass spectrometry. These approaches alone are not feasibly scaled to explore the large sequence space of DNA oligomer templates for AgN-DNAs.This account describes recent fundamental advances in AgN-DNA science that have been enabled by high throughput synthesis and fluorimetry together with detailed analytical studies of purified AgN-DNAs. First, short introductions to nanocluster chemistry and AgN-DNA basics are presented. Then, we review recent large-scale studies that have screened thousands of DNA templates for AgN-DNAs, leading to discovery of distinct classes of these emitters with unique cluster core compositions and ligand chemistries. In particular, the discovery of a new class of chloride-stabilized AgN-DNAs enabled the first ab initio calculations of AgN-DNA electronic structure and present new approaches to stabilize these emitters in biologically relevant conditions. Near-infrared (NIR) emissive AgN-DNAs are also found to exhibit diverse structures and properties. Finally, we conclude by highlighting recent proof-of-principle demonstrations of NIR AgN-DNAs for targeted fluorescence imaging. Continued efforts may future push AgN-DNAs into the tissue transparency window for fluorescence imaging in the NIR-II tissue transparency window
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