Session D20: Bionanotechnology

Multifunctional nanoparticles (Au@SiO$_{2}$@Y$_{2}$O$_{3}$:Er$^{3+})$ for biological and photonic application

Due to plasmon at the surface, the absorption and scattering of electromagnetic radiation by metal nanoparticles are strongly enough. These properties provide the potential of designing multifunctional nanoparticles which are optically active for simultaneous molecular imaging and photothermal cancer therapy. Gold nanorods with suitable aspect ratios can absorb and scatter strongly in the NIR region. In the present work, we have demonstrated the application of multifunctional nanoparticles (Au@SiO$_{2}$@Y$_{2}$O$_{3}$:Er$^{3+})$ as contrast agents for both molecular imaging and photo thermal therapy. These multifunctional naoparticles has shown the enhancement in Er$^{3+}$fluorescence through plasmon interaction and enhancement in Raman spectrum, which made these nanoparticles potential for biosensor for detecting the biological and chemical molecule.   

Fundamental Interactions between Deoxyribonucleic Acid (DNA) Oligomers and Au Nanoparticles: Experimental and Theoretical Studies

\textbf{E}xperimental and theoretical investigations were performed to understand the nature of fundamental interactions between gold nanoparticles (GNPs) and single stranded DNA (ss-DNA). Atomic force microscopic imaging and UV-Visible spectroscopic measurements revealed binding of NPs with ss-DNA under mildly acidic conditions.. \textit{Ab initio} quantum chemical calculations within the framework of density functional theory provided a possible charge transfer pathway from the DNA base guanine to Au atoms and thus characterizing the interaction as electrostatic. The calculations outline the possible effect of the presence of other bases to guanine mediated charge transfer. Specifically, the presence of an adenine base alters the charge localization at the guanine base and thus prevents charge transfer to NPs.   

Modeling the effect of dynamic surfaces on membrane penetration

The development of nanoscale materials for targeted drug delivery is an important current pursuit in materials science. One task of drug carriers is to release therapeutic agents within cells by bypassing the cell membrane to maximize the effectiveness of their payload and minimize bodily exposure. In this work, we use coarse-grained simulations to study nanoparticles (NPs) grafted with hydrophobic and hydrophilic ligands that rearrange in response to the amphiphilic lipid bilayer. We demonstrate that this dynamic surface permits the NP to spontaneously penetrate to the bilayer midplane when the surface ligands are near an order-disorder transition. We believe that this work will lead to the design of new drug carriers capable of non-specifically accessing cell interiors based solely on their dynamic surface properties. Our work is motivated by existing nanoscale systems such as micelles, or NPs grafted with highly mobile ligands or polymer brushes.   

Microsphere whispering gallery optical resonators for biomedical microfluidic devices

These resonators are potential candidates for broad application range as sensors of various physical quantities, and as key elements for photonic and optomechanical systems. Most of the biomedical applications involve deployment of resonators in fluidic environment. However, closeness of refractive indices of sphere $n_{s}$ and fluid $n_{f}$ obstructs excitation of the resonant modes. Moreover, an attempt to increase $n_{s}$ can deteriorate coupling of light between fiber and sphere. To address these challenges we explore a series of high-Q resonators using a specially developed tapered optical microfiber microfluidic platform. The coupling strength between the cavity and the microfiber taper is shown to depend on the contact position of the microsphere along the taper and on the refractive index contrast between the microsphere and the fluid. We demonstrate that barium titanate glass beads with $n_{s}\sim2$ can be suitable for practical tasks.   

Utilizing nonlinear optical properties in nanoparticles for imaging

Optical phase conjugation is a nonlinear effect in which light incident upon a nonlinear medium may be conjugated so that the output signal is in the opposite direction of the input, as seen in four-wave mixing. Recently, we have seen that these nonlinear effects may still be seen in various nanocrystals and nanoparticles. Barium titanate (BaTiO3) is a good candidate for phase conjugation on the nano-scale, because of its large third order susceptibility. BaTiO3 particles of varying size are synthesized through precipitation and hydrothermal methods and analyzed optically and morphologically. The nonlinear absorption, four wave mixing signal in the forward and counter-propagating geometries, and third order susceptibilities are characterized in both the visible and infrared. Possible uses for the unique optical properties of these nanoparticles in imaging, microscopy, and photonics will also be discussed.   

Gold Nanostars for Photo-Thermal Ablation of Single Neurons

Nanoparticle mediated photo-thermal ablation therapy is a technique for removing cells within a tissue with minimal collateral damage. It works by exciting the surface plasmon resonance of metallic nanoparticles so there is an amplification of the absorption of the incident electromagnetic field which is then transformed into heat and results in photo-thermal ablation. Little is known about its effects at the single-cell level. We fabricated various sized and shaped gold nanoparticles, including nanostars, with a surface plasmon mode in the near infrared. Neurons of mouse cerebellar slices internalize bare nanostars during incubation periods of $<$3 hrs. We imaged the slices and excited surface plasmon mode of the nanostars. Our results show that we are capable of destroying individual nanostar containing cells without affecting the neighbors. Other shapes attach to the cell membrane but are not internalized. Therefore nanoparticles can provide a technique for a neuron single-cell photo-thermal without any functionalization.   

Biochemically Selective Nanoarrays: From Protein-DNA Interactions to Bio-Inorganic Nanoscale Assembly

The ability to control the arrangement of both biomolecules and bio-inorganic structures on surfaces with nanometer resolution is of great interest in the field of nanoscience and nanotechnology. Nanopatterned arrays of biomolecules can offer unmatched sensitivity in molecular diagnostics. Furthermore, templated assembly of bio-inorganic structures at the nanoscale makes possible interesting quantum optical structures, including switchable photonic cavities. Here we describe different strategies to control the immobilization of single- and double-stranded DNA, as well as quantum dots, on nanopatterned surfaces, with features down to the sub-30nm regime. The bio-functional chemistry allows for the formation of non-sterically hindered DNA nanodomains where the dsDNA attached to the nanodots is accessible and maintains its native conformation, as confirmed by restriction enzymes studies at the single molecule level. We will further highlight the broader utility of such nanopatterned surfaces for the self-organization of quantum dots, demonstrating the ability to both biochemically and covalenty assemble single quantum dots on our nanopatterns.   

Nanoscale open-ended coaxial line proximity sensor array for spatio-temporal impedance imaging

We describe the development of a dielectric impedance measurement array comprised of open-ended nanoscale coaxial proximity sensors. The device offers the capability of on-chip dielectric impedance tomography for imaging \emph{e.g.} biological cells with $\sim$micron pixel density. Computer simulations of the response of individual pixels and of discrete arrays to changes in dielectric properties of proximate media are presented. Experiments with biological cells on 1st-generation arrays will be discussed.   

Nonlinear Optical Properties of ZnO for BioimagingCell and Cell Destruction

As of recent years nanotechnology has been at the forefront of scientific research. It promises to have a broad range of applications from turning unhealthy foods into health foods, making computers faster and curing cancer. We present results on using nonlinear optical processes of ZnO nano-crystals to detect, track and destroy cells. By incorporating ZnO into a hydrophobic nano-hydrogel matrix with trace amounts of H$_{2}$O$_{2}$, we can attach antibodies or microRNA for specific cell targeting and, using the heat generating properties of the third order nonlinear process, release H$_{2}$O$_{2}$ in the cell causing instant cell death. Theoretically, with the appropriate sequence for microRNA or the appropriate antibodies, we could target cancer cells in the body and destroy them. This presentation gives our results until now.   

Polymeric Nanoelectrodes for Investigating Cellular Adhesion

Polyethylene dioxythiophene nano-filaments were grown on lithographic electrode arrays by the recently developed directed electrochemical nanowire assembly technique. These filaments are firmly attached to the electrode but are not attached to the glass substrate. Hence, they behave like cantilevered rods (with one free end). Individual cells of the slime mold \textit{Dictystolium discoideum} initiate contact by extending pseudopods to the nanoelectrodes when cultured on the electrode arrays. Scanning electron micrographs of the interfaces show the contact area to be of the order of 0.1 $\mu $m$^{2}$. Confocal images reveal the focal adhesions in the cell-electrode contact region. Deflection of the nanoelectrode by an individual cell can be used to measure the force exerted by the cell. Recent results on this innovative force sensing approach will be discussed.   

Detecting Lyme disease using antibody-functionalized carbon nanotubes

We combine antibodies for Lyme flagellar protein with carbon nanotube transistors to create an electronic sensor capable of definitive detection of Lyme disease. Over 35,000 cases of Lyme disease are reported in the United States each year, of which more than 23 percent are originally misdiagnosed. Rational design of the coupling of the biological system to the electronic system gives us a flexible sensor platform which we can apply to several biological systems. By coupling these antibodies to carbon nanotubes in particular, we allow for fast, sensitive, highly selective, electronic detection. Unlike antibody or biomarker detection, bacterial protein detection leads to positive identification of both early and late stage bacterial infections, and is easily expandable to environmental monitoring.   

Fluorescence-Based DNA-Nanotube Platform with Single Molecule Resolution

We have developed an experimental platform to control and modify the DNA on a DNA-Single Walled Nanotube (SWNT) complex for the purpose of detecting labeled and unlabeled protein-DNA interactions via visible fluorescence. By exploiting the distance-dependent photophysical interaction between organic fluorophores and the surface of a SWNT as the sensing mechanism, fluorophore-conjugated DNA-SWNTs are immobilized and observed using single molecule-total internal reflection microscopy. By analyzing the number of molecules, photobleaching steps and the absolute size of the observed DNA-SWNTs, we have confirmed the presence of a duplex, partial duplex and single-strand DNA scaffold on the SWNT surface using both nucleic acids and proteins as probes. Our approach offers multiple experimental schemes to extend the current use of carbon nanotubes for applications involving the interaction with biologically relevant molecules.   

Selective Intracellular Activation by Designing pH-Sensitive and Tunable Fluorescent Nanoparticle

Integration of nanotechnology with molecular biology and medical imaging has propelled the development of various nanoscopic imaging probes and targeted therapeutics. Despite great advances, it remains a formidable challenge to create highly biointeractive nanosystems that can respond to subtle changes in physiological stimuli (e.g. pH, enzymes) to achieve desired biological specificity. Here we report a set of robust, pH-activatable micelle nanoprobes with tunable pH transitions in the physiological range. These nanoprobes have a fast fluorescence response ($<$5 ms), up to 55-fold increase of emission intensity between OFF and ON states, and only require $<$0.25 pH unit for activation (vs. 2 pH unit for small molecular dyes). Nanoprobes with different transition pH can be selectively activated in specific endocytic compartments such as early endosomes or lysosomes. This capability allows for the development of pH-activatable imaging probes or nanocarriers that can target specific subcellular organelles for therapy.   

Formation of Lipid Bilayer Membrane including Ion Channels on Graphene

Lipid bilayer membrane on a solid electrode has been extensively utilized to study membrane proteins. Recently, graphene has drawn an attention as a transparent and high conductive electrode compatible with biological systems. Herein, we report the successful formation of lipid membrane including ion channels on graphene. In this method, graphene was functionalized by biocompatible molecular layers and utilized as a substrate to support lipid bilayer membrane including ion channels. The functionality of ion channels incorporated in the lipid bilayer membrane was studied via the electrochemical impedance spectroscopy. This lipid membrane-coated graphene structure can be a versatile platform for various applications such as bio-sensing and in vitro drug screening.   

Aptamer sandwich-based carbon nanotube sensors for single-carbon-atomicresolution detection of non-polar small molecular species

Portable sensor platforms are crucial for the on-site monitoring of disease-related metabolites, environmental pollutants and food toxicants. However, it is still difficult to build highly-sensitive and selective sensor platforms for small molecular detection. We developed an aptamer sandwich-based carbon nanotube sensor, where aptamers were utilized to capture target molecules as well as to enhance the sensor signals. Using this strategy, we successfully demonstrated the detection of non-polar bisphenol A molecules with a picomolar sensitivity and single-carbon-atomic resolution. Furthermore, by modifying the labeling aptamer with additional biotin, we enhanced the detection limit of our sensors for one hundred times. These results overcome the fundamental limitation of general FET-based sensors and should make a major breakthrough in various applications such as environmental protection and food safety.