Fluorescent silica manoparticles with well-separated intensity distributions from batch reactions

Silica chemistry provides pathways to uniquely tunable nanoparticle platforms for biological imaging. It has been a long-standing problem to synthesize fluorescent silica nanoparticles (SNPs) in batch reactions with high and low fluorescence intensity levels for reliable use as an intensity barcode, which would greatly increase the number of molecular species that could be tagged intracellularly and simultaneously observed in conventional fluorescence microscopy. Here, employing an amino-acid catalyzed growth, highly fluorescent SNP probes were synthesized with sizes <40 nm and well-separated intensity distributions, as mapped by single-particle imaging techniques. A seeded growth approach was used to minimize the rate of secondary particle formation. Organic fluorescent dye affinity for the SNP during shell growth was tuned using specifics of the organosilane linker chemistry. This work highlights design considerations in the development of fluorescent probes with well-separated intensity distributions synthesized in batch reactions for single-particle imaging and sensing applications, where heterogeneities across the nanoparticle ensemble are critical factors in probe performance

Fluorescent silica manoparticles with well-separated intensity distributions from batch reactions

Silica chemistry provides pathways to uniquely tunable nanoparticle platforms for biological imaging. It has been a long-standing problem to synthesize fluorescent silica nanoparticles (SNPs) in batch reactions with high and low fluorescence intensity levels for reliable use as an intensity barcode, which would greatly increase the number of molecular species that could be tagged intracellularly and simultaneously observed in conventional fluorescence microscopy. Here, employing an amino-acid catalyzed growth, highly fluorescent SNP probes were synthesized with sizes <40 nm and well-separated intensity distributions, as mapped by single-particle imaging techniques. A seeded growth approach was used to minimize the rate of secondary particle formation. Organic fluorescent dye affinity for the SNP during shell growth was tuned using specifics of the organosilane linker chemistry. This work highlights design considerations in the development of fluorescent probes with well-separated intensity distributions synthesized in batch reactions for single-particle imaging and sensing applications, where heterogeneities across the nanoparticle ensemble are critical factors in probe performance

Characterizing and Controlling Optical Properties of Nanomaterials for Applications in Optical Super-Resolution Microscopy, Cancer Theranostics, and Arts and Architecture

Optical properties of nano-sized materials (optical nanomaterials) can either be the result of interactions of light with periodic material structures, e.g. in colloidal or block copolymer based photonic crystals, or stem from the incorporation of photoactive molecules into nano-sized, optically inactive materials, e.g. fluorescent dyes in organic-inorganic hybrid silica nanoparticles. This dissertation introduces representatives of both material classes. The first case described here are ultrasmall (sub-10 nm) amorphous silica nanoparticles (SNPs) covalently encapsulating photoactive organic moieties. Such particles, referred to as Cornell prime dots (C’ dots), have already shown tremendous success in the safe diagnosis of cancer in human clinical trials with melanoma patients. However, their full potential in the lab and clinical setting, as diagnostic as well as therapeutic probes, has not yet been fully explored. Furthermore, comprehensive understanding of particle structure-property correlations, i.e. core and surface properties, remains limited. In the first part of this dissertation, a new approach for characterizing the particles is introduced using a combination of fluorescence correlation spectroscopy (FCS), single particle bleaching, and high-performance liquid chromatography (HPLC). It is shown that the net charge of organic dyes introduced in the synthesis is a main contributor to chemical surface heterogeneities of the particles. In the second part of this thesis a new class of ultrasmall theranostic silica nanoparticles for the application in photodynamic therapy is described. It is demonstrated that high effective singlet oxygen quantum yields can be achieved, while keeping particle size below the threshold for renal clearance (sub-10 nm). Next, the concept of particle molecular photo-engineering (PMPE) is introduced as a means to tailor photophysical properties of organic dye encapsulating SNPs. By precisely engineering the chemical composition of the amorphous silica particle core network around encapsulated organic dyes using specific functional groups, i.e. mercaptopropyl or iodopropyl groups, dye transient dark states can be controlled which in turn enables super-resolution microscopy and substantially enhanced singlet oxygen quantum yields, respectively. The second class of optical nanomaterials in this dissertation is a self-assembled poly(styrene-block-tert-butyl methacrylate) (StB) diblock copolymer with a photonically active lamellar structure. Bottom-up self-assembly processes provide highly desired and cost-effective methods for the fabrication of large scale/area photonic coatings, making such materials interesting candidates for applications in architecture and design. In part three of this thesis the synthesis of ultralarge molar mass StB block copolymers and their application as iridescent and transparent thin film coatings is described. Development of a casting-lamination process to apply such coatings to window panels allowed the first architectural use of block copolymers as an iridescent façade in the form of the art installation A needle woman: Galaxy Was a Memory, Earth is a Souvenir by artist Kimsooja. Quantitative characterization of structural as well as optical properties of these coatings establishes that the block copolymer films behave as volume-phase gratings with grating periodicities close to 300 nm

Dynamics of Nanoparticles in Entangled Polymer Solutions

The mean square displacement ⟨<i>r</i>²⟩ of nanoparticle probes dispersed in simple isotropic liquids and in polymer solutions is interrogated using fluorescence correlation spectroscopy and single-particle tracking (SPT) experiments. Probe dynamics in different regimes of particle diameter (<i>d</i>), relative to characteristic polymer length scales, including the correlation length (ξ), the entanglement mesh size (<i>a</i>), and the radius of gyration (<i>R</i>_g), are investigated. In simple fluids and for polymer solutions in which <i>d</i> ≫ <i>R</i>_g, long-time particle dynamics obey random-walk statistics ⟨<i>r</i>²⟩:<i>t</i>, with the bulk zero-shear viscosity of the polymer solution determining the frictional resistance to particle motion. In contrast, in polymer solutions with <i>d</i> < <i>R</i>_g, polymer molecules in solution exert noncontinuum resistances to particle motion and nanoparticle probes appear to interact hydrodynamically only with a local fluid medium with effective drag comparable to that of a solution of polymer chain segments with sizes similar to those of the nanoparticle probes. Under these conditions, the nanoparticles exhibit orders of magnitude faster dynamics than those expected from continuum predictions based on the Stokes–Einstein relation. SPT measurements further show that when <i>d</i> > <i>a</i>, nanoparticle dynamics transition from diffusive to subdiffusive on long timescales, reminiscent of particle transport in a field with obstructions. This last finding is in stark contrast to the nanoparticle dynamics observed in entangled polymer melts, where X-ray photon correlation spectroscopy measurements reveal faster but hyperdiffusive dynamics. We analyze these results with the help of the hopping model for particle dynamics in polymers proposed by Cai et al. and, on that basis, discuss the physical origins of the local drag experienced by the nanoparticles in entangled polymer solutions