Rational Design Of Sers Active Silica Coated Silver Nanoparticles As A Versatile Platform For Semi Quantitative Bio Imaging PDF Download

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Rational Design of SERS Active Silica Coated Silver Nanoparticles as a Versatile Platform for Semi-quantitative Bio-imaging

Rational Design of SERS Active Silica Coated Silver Nanoparticles as a Versatile Platform for Semi-quantitative Bio-imaging
Author: Louise Rocks
Publisher:
Total Pages: 0
Release: 2012
Genre:
ISBN:

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In recent years there has been an increased demand for real-time detection of specific biological species and interactions within a meaningful environment. Surface enhanced Raman scattering (SERS) from metallic nanoparticles represents an approach under development with added advantages over fluorescence. One such benefit is the narrower vibrational bands in SERS compared to fluorescence which increases potential for simultaneous detection of more than one species. The use of metallic nanoparticles in Raman enhancement is hindered by non-specific adsorption of contaminating species and uncontrolled aggregation in vivo. Silica encapsulation of the nanoparticles results in a biocompatible and robust substrate with consistent surface chemistry. While gold nanoparticles have been shelled in silica by many different methods, transfer of encapsulation methods to silver has not been possible due to the reduced chemical stability of silver. New surface chemistries are therefore required to achieve reproducible, silica encapsulated silver nanoparticles. Tri-functional molecules were synthesised which stabilise the silver nanoparticle core, act as (resonance) Raman reporters and provide suitable precursors for subsequent silica encapsulation. Subsequent bio-functionalisation of these nanoparticles, by covalent attachment of proteins, generates SERS active bioimaging nanoparticles. Raman mapping of biological samples has been used for ex vivo detection and imaging of the inflammatory marker tumour necrosis factor. Semi-quantitative discrimination, of cerebral tissue sections, was achieved between mice infected with experimental cerebral malaria and uninfected controls. These results were produced using both 632.8 nm and 514.5 nm excitation wavelengths. In this work, a sensitive SERS based approach to biomolecule imaging has been developed. Successful targeting of TNF using silver nanoparticles, and excitation wavelengths in the visible region, may provide advantages over the use of gold in a wide range of SERS based applications.


The Rational Design and Lithographic Fabrication of Surface Enchanced [i.e. Enhanced] Raman Spectroscopy Substrates

The Rational Design and Lithographic Fabrication of Surface Enchanced [i.e. Enhanced] Raman Spectroscopy Substrates
Author:
Publisher:
Total Pages: 148
Release: 2008
Genre:
ISBN:

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The analytical capabilities of surface-enhanced Raman spectroscopy (SERS) reside in the performance characteristics of the SERS-active substrate. Signal enhancement observed in SERS is attributable to the presence of noble metal nanostructures on substrate surfaces. The rational design and control of variables such as shape and size, and distribution, density, and spacing of these nanostructures can lead to substrates that have greater analytical sensitivity and yield more reproducible enhancement. Through systematic control of the morphology of our SERS substrates, we have created ordered periodic arrays as well as random aggregates of nanoscale particles using electron beam lithography (EBL). A unique aspect of these EBL-created substrates is that the morphology is known with great precision. Once fabricated, the arrays and/or aggregates are coated with a SERS-active noble metal through physical vapor deposition (PVD). Both the uniform and random lithographically produced nanopatterns are studied by surface enhanced Raman spectroscopy to examine the Stokes responses of various analytes, while scanning electron microscopy (SEM) is used to examine pattern surfaces post lithographic development and post noble metal deposition. In the case of the ordered structures, raw and normalized SERS data is seen to correlate with data from simple electrostatic calculations as well as the broad background continuum underlying each spectrum collected. Borrowing from the biological concepts of cloning and combinatorial chemistry, random morphology patterns are designed and spectrally mapped to locate "hot spots" within aggregates. Regardless of the type of substrate, ordered or random, by using EBL, the substrates can be reproducibly fabricated, yielding consistent analyte environments each time the substrate is created.


Investigation and Design of SERS Active Nanoparticle Assemblies Via Biological Interactions

Investigation and Design of SERS Active Nanoparticle Assemblies Via Biological Interactions
Author: Derek Craig
Publisher:
Total Pages: 0
Release: 2013
Genre:
ISBN:

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The overarching theme of this research was to further the understanding of the interactions of both the proteome and the glycome. An initial soft focus was placed upon increasing the stability of nanoparticles via the design of novel linker chemistries for nanoparticle functionalisation. From these initial studies, the synergic theme of studying different types of biological interactions using SERS has come to the forefront of this research. Novel nanotag synthesis has been detailed using a one-step functionalisation methodology. The stability of these nanotags has been investigated and found to be on par with the stability achieved using the current leading methods of nanotag functionalisation. Reproducible SERS spectra have been obtained in the presence of high electrolyte concentrations as well as in highly acidic conditions. These novel nanotags have been employed to differing degrees of success in a number of immunoassay formats. Successful detection has been achieved in a TMB ELISA format indicating that the biological integrity of the biomolecules attached to these nanotags remains intact following their functionalisation. Following the success of the linkers devised for nanotags synthesis several novel short chain carbohydrate linker groups were devised. These carbohydrate linkers were then attached to both gold and silver nanoparticle for deployment in the formation of nanoparticle assemblies mediated by the interaction with carbohydrate specific proteins known as lectins. The formation of these nanoparticle assemblies has shown to be dependent on the concentration of lectin present and as such, linear ranges of detection have been achieved using both extinction spectroscopy and SERS, which are unrivalled when using current detection methods. The converse of this approach, lectin functionalised nanoparticles, were employed as molecular imaging agents for the elucidation of the surface carbohydrate composition of multiple cell lines. These studies have been extended to detecting disease directed cellular modifications via binding to over expressed sialic acid residues present on prostate cancerous cells. This has elicited a method by which it may be possible to discriminate between both cancerous and non-cancerous cells in a clinical environment.


Cerium Oxide Nanoparticles and Gadolinium Integration

Cerium Oxide Nanoparticles and Gadolinium Integration
Author: Peter Eriksson
Publisher: Linköping University Electronic Press
Total Pages: 48
Release: 2019-08-29
Genre:
ISBN: 9176850293

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A challenging task, in the area of magnetic resonance imaging is to develop contrast enhancers with built-in antioxidant properties. Oxidative stress is considered to be involved in the onset and progression of several serious conditions such as Alzheimer’s and Parkinson’s disease, and the possibility to use cerium-contained nanoparticles to modulate such inflammatory response has gained a lot of interest lately. The rare earth element gadolinium is, due to its seven unpaired f-electrons and high symmetry of the electronic state, a powerful element for contrast enhancement in magnetic resonance imaging. Chelates based on gadolinium are the most commonly used contrast agents worldwide. When introducing external contrast agents there is always a risk that it may trigger inflammatory responses, why there is an urgent need for new, tailor-made contrast agents. Small sized cerium oxide nanoparticles have electronic structures that allows coexistence of oxidation states 3+ and 4+ of cerium, which correlates to applicable redox reactions in biomedicine. Such cerium oxide nanoparticles have recently shown to exhibit antioxidant properties both in vitro and in vivo, via the mechanisms involving enzyme mimicking activity. This PhD project is a comprehensive investigation of cerium oxide nanoparticles as scaffold materials for gadolinium integration. Gadolinium is well adopted into the crystal structure of cerium oxide, enabling the combination of diagnostic and therapeutic properties into a single nanoparticle. The main focus of this thesis project is to design cerium oxide nanoparticles with gadolinium integration. A stepwise approach was employed as follows: 1) synthesis with controlled integration of gadolinium, 2) material characterization by means of composition crystal structure, size, and size distribution and 3) surface modification for stabilization. The obtained nanoparticles exhibit remarkable antioxidant capability in vitro and in vivo. They deliver strongly enhanced contrast per gadolinium in magnetic resonance imaging, compared to commercially available contrast agents. A soft shell of dextran is introduced to encapsulate the cerium oxide nanoparticles with integrated gadolinium, which protects and stabilizes the hard core and to increases their biocompatibility. The dextran-coating is clearly shown to reduce formation of a protein corona and it improves the dispersibility of the nanoparticles in cell media. Functionalization strategies are currently being studied to endow these nanoparticles with specific tags for targeting purposes. This will enable guidance of the nanoparticles to a specific tissue, for high local magnetic resonance contrast complemented with properties for on-site reduced inflammation. In conclusion, our cerium oxide nanoparticles with integrated gadolinium, exhibit combined therapeutic and diagnostic, i.e. theragnostic capabilities. This type of nanomaterial is highly promising for applications in the field of biomedical imaging.


Passive Mass Transport for Direct and Quantitative SERS Detection Using Purified Silica Encapsulated Metal Nanoparticles

Passive Mass Transport for Direct and Quantitative SERS Detection Using Purified Silica Encapsulated Metal Nanoparticles
Author: Binaya Kumar Shrestha
Publisher:
Total Pages: 161
Release: 2015
Genre: Nanoparticles
ISBN:

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This thesis focuses on understanding implications of nanomaterial quality control and mass transport through internally etched silica coated nanoparticles for direct and quantitative molecular detection using surface enhanced Raman scattering (SERS). Prior to use, bare nanoparticles (partially or uncoated with silica) are removal using column chromatography to improve the quality of these nanomaterials and their SERS reproducibility. Separation of silica coated nanoparticles with two different diameters is achieved using Surfactant-free size exclusion chromatography with modest fractionation. Next, selective molecular transport is modeled and monitored using SERS and evaluated as a function of solution ionic strength, pH, and polarity. Molecular detection is achieved when the analytes first partition through the silica membrane then interact with the metal surface at short distances (i.e., less than 2 nm). The SERS intensities of unique molecular vibrational modes for a given molecule increases as the number of molecules that bind to the metal surface increases and are enhanced via both chemical and electromagnetic enhancement mechanisms as long as the vibrational mode has a component of polarizability tensor along the surface normal. SERS signals increase linearly with molecular concentration until the three-dimensional SERS-active volume is saturated with molecules. Implications of molecular orientation as well as surface selection rules on SERS intensities of molecular vibrational modes are studied to improve quantitative and reproducible SERS detection using internally etched Ag@Au@SiO2 nanoparticles. Using the unique vibrational modes, SERS intensities for p-aminothiophenol as a function of metal core compositions and plasmonics are studied. By understanding molecular transport mechanisms through internally etched silica matrices coated on metal nanoparticles, important experimental and materials design parameters are learned, which can be subsequently applied to the direct and quantifiable detection of small molecules in real samples without the need for lengthy separations and assays.


Dynamic Signal Processing for the Characterization of SERS-active Nanoparticles

Dynamic Signal Processing for the Characterization of SERS-active Nanoparticles
Author: Brandon Scott
Publisher:
Total Pages: 100
Release: 2015
Genre: Microspheres
ISBN: 9781339070582

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Since its discovery in the 1970's, Surface-Enhanced Raman Scattering (SERS) has aided the development of analytical methods for a wide variety of applications. Raman scattering enhancements of up to 7 orders of magnitude permit trace detection and identification of analytes. Furthermore, the ease of use, affordability, and portability of modern Raman instrumentation makes it a viable candidate for analytical chemistry. We developed a new direct and indirect SERS assay with buoyant silica microspheres, termed Lab-on-a-Bubble. Direct assays involve coating silica bubbles with nanoparticles and indirect assays pair bubbles with Raman reporters in a sandwich assay. These assays have the unique advantage of buoyancy-driven detection and selection of analytes in solution. To evaluate these assays we looked at cyanide and 5,5'-dithiobis(2-nitrobenzoic acid) (direct) and cholera (indirect). The second part of this dissertation relates to particle aggregation. This work follows a report from Wustholz et al. that suggested SERS enhancement occurs near gap regions in nanoparticle aggregates, termed hotspots. Aggregates are difficult to study due to their small size. They can be probed in vacuum by electron microscopy but they cannot be observed directly with light microscopy in solution. We developed a statistical method for specific extraction of SERS signals from colloidal SERS active nanoparticles, termed dynamic SERS (DSERS). Our first study examined a strongly coordinating monolayer, 4-mercaptopyridine, which exhibits unique SERS spectra in acid and base but invariant DSERS spectra. Our interpretation was that DSERS results showed only molecules in the gap region between nanoparticles. Continued work examined a non-coordinating (thiophenol) and a weakly coordinating (4-mercaptophenol) monolayer and their role in aggregation of NPs. Thiophenol was observed to not produce unique DSERS spectra as a function of pH. In contrast to 4-mercaptopyridine, we found that 4-mercaptophenol produced different DSERS spectra as a function of pH. We also developed additional statistical methods to complement DSERS results: correlograms and frequency shift histograms. In addition to these studies we began looking at viologen-functionalized SERS substrates for the detection of polycyclic aromatic hydrocarbons and chiral molecules. While this work is very preliminary we observed differences in SERS spectra of (DL)-, (D)- and (L)-cysteine adsorbed to silver nanoparticles coated with chiral viologen. We also observed adsorption of polycyclic aromatic hydrocarbons on these substrates.


Rational Design and Advanced Fabrication of Metallic Nanostructures for Surface-enhanced Raman Spectroscopy

Rational Design and Advanced Fabrication of Metallic Nanostructures for Surface-enhanced Raman Spectroscopy
Author: Betty Cristina Galarreta
Publisher:
Total Pages: 326
Release: 2011
Genre:
ISBN:

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One of the main challenges in analytical science and technology is to develop devices that provide unambiguously the chemical nature of the material of interest with the minimum intrusiveness, the smallest amount of analyte, and the shortest acquisition time. Among the promising methods for such purpose, optical spectroscopy such as surface-enhanced Raman scattering is considered a suitable option. This spectroscopic technique takes advantage of the interaction between an optical field and metallic nanostructures to magnify the electromagnetic field in the vicinity of the nanostructure, resulting in an amplified signal of the vibrational fingerprints of the adsorbed molecules onto the metallic surface. In this Thesis, the rational design and fabrication of gold nanostructures optimized to probe molecular systems, at the monolayer level in a variety of configurations, is described. Using advanced nanofabrication techniques, two-dimensional arrays of metallic nanostructures were inscribed onto glass slides. The fabricated SERS platforms were first physically and optically characterized. Then, a rational analysis of the properties was performed through numerical calculations and experimental measurements, to estimate the polarization dependence of such nanostructures. The results led toward the optimization of the SERS platforms, and to the study of different complex surface molecular systems. Finally, these platforms were embedded in a microfluidic device for in-situ probing of molecules opening the possibility to develop micro total analysis in combination with Raman measurements.


Novel Approaches to Prepare and Utilize Surface-enhanced Raman Spectroscopy (SERS) Substrates

Novel Approaches to Prepare and Utilize Surface-enhanced Raman Spectroscopy (SERS) Substrates
Author:
Publisher:
Total Pages: 185
Release: 2008
Genre:
ISBN:

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Over the past few decades, surface enhanced Raman spectroscopy (SERS) has garnered respect as an analytical technique with significant chemical and biological applications. SERS is important for the life sciences because it can provide trace level detection and a high level of molecular structure information. The development of quantitative, highly sensitive substrates requires control over size, shape, and position of metal nanoparticles which function as the SERS active medium. Thus, creating and successfully implementing a sensitive, reproducible, and robust SERS active substrate continues to be a challenging task. Its future development depends critically on techniques for lithography and nanofabrication. Herein, we report a novel method for SERS that is based upon using colloidal silver nanoparticles in a multiplexed microfluidics (MMFs) platform. The MMF is created in polydimethylsiloxane (PDMS) polymer material and used to perform parallel, high throughput, and sensitive detection/identification of single or various analytes under easily manipulated conditions. A facile passive pumping method is used to deliver samples into the channels under flowing conditions that are highly conducive for SERS measurments. Also an unconventional nanofabrication approach is modified to produce efficient SERS substrates. Metallic nanopatterns of silver discs are transferred from a stamp onto PDMS to create nanocomposite substrates with regular periodic morphologies. The stamp with periodic arrays of square, triangular, and elliptical pillars is created via Electron Beam Lithography of ma-N 2403 resist. A modified cyclodextrin is thermally evaporated on the stamp to overcome the adhesive nature of the ebeam resist and to function as a releasing layer. Subsequently, the stamp is over coated with Ag by physical vapor deposition at a controlled rate and thickness and used directly for nanotransfer printing (nTP). Stamps, substrates, and the efficiency of the nTP process were explored by SEM. Ag nano-disc-PDMS substrates are studied by SERS using Rhodamine 6G as the probe analyte. The SERS response of metallic nano-discs of various shapes/sizes on the original stamp is compared to the corresponding nTP substrates. We demonstrate that physical manipulation of the PDMS post nTP can be used to alter morphology. Additionally, stamps are shown to be reusable after the nTP process.


Rationally Designed Substrates for SERS Biosensing

Rationally Designed Substrates for SERS Biosensing
Author: Bo Yan
Publisher:
Total Pages: 350
Release: 2013
Genre:
ISBN:

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Abstract: The large electromagnetic field enhancement provided by nanostructured noble metal surfaces forms the foundation for a series of enabling optical analytical techniques, such as surface enhanced Raman spectroscopy (SERS), surface enhanced IR absorption spectroscopy (SEIRA), surface enhanced fluorescent microscopy (SEF), to name only a few. Critical sensing applications have, however, other substrate requirements than mere peak signal enhancement. The substrate needs to be reliable, provide reproducible signal enhancements, and be amenable to a combination with microfluidic chips or other integrated sensor platforms. These needs motivate the development of engineerable SERS substrate "chips" with defined near- and far-field responses. In this dissertation, two types of rationally designed SERS substrates - nanoparticle cluster arrays (NCAs) and SERS stamp - will be introduced and characterized. NCAs were fabricated through a newly developed template guided self-assembly fabrication approach, in which chemically synthesized nanoparticles are integrated into predefined patterns using a hybrid top-down/bottom-up approach. Since this method relies on chemically defined building blocks, it can overcome the resolution limit of conventional lithographical methods and facilitates higher structural complexity. NCAs sustain near-field interactions within individual clusters as well as between entire neighboring clusters and create a multi-scale cascaded E-field enhancement throughout the entire array. SERS stamps were generated using an oblique angle metal deposition on a lithographically defined piston. When mounted on a nanopositioning stage, the SERS stamps were enabled to contact biological surfaces with pristine nanostructured metal surfaces for a label-free spectroscopic characterization. The developed engineered substrates were applied and tested in critical sensing applications, including the ultra-trace detection of explosive vapors, the rapid discrimination of bacterial pathogens, and the label-free monitoring of the enzymatic degradation of pericellular matrices of cancer cells.


A Chemical Free Approach for Increasing the Biochemical Surface-enhanced Raman Spectroscopy (SERS)-based Sensing Capabilities of Colloidal Silver Nanoparticles

A Chemical Free Approach for Increasing the Biochemical Surface-enhanced Raman Spectroscopy (SERS)-based Sensing Capabilities of Colloidal Silver Nanoparticles
Author: Kevin Michael Dorney
Publisher:
Total Pages: 170
Release: 2014
Genre: Nanoparticles
ISBN:

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The unique optoelectronic properties of silver nanoparticles (AgNPs) have led to their explosive use in a multitude of both research and industrial settings in recent years. Localized surface plasmon resonance (LSPR) exhibited by AgNPs has been exploited extensively as a nano-scale probe in a variety of spectroscopic detection modalities, particularly in surface-enhanced Raman spectroscopy (SERS). The SERS effect is highly dependent upon the LSPR interaction with optical laser frequencies, thus optimization of LSPR via specific control of AgNP dimensionality and composition of the surrounding medium is vital for increasing the efficacy of SERS-based nano-sensing. This work aimed to augment LSPR of AgNPs by applying the chemical free technique of tangential flow filtration (TFF) to a Creighton colloid of spherical AgNPs and specifically tailoring their size-distribution, concentration, and purity. First, a large batch of Creighton AgNPs (1-100 nm in diameter) were size-selected (20 nm and 12 nm in average diameter), concentrated, and purified via a three-step TFF procedure and characterized for effectiveness as SERS substrates in pre-resonance, resonance, and single-molecule resonance conditions for a Raman reporter, rhodamine 6G. The 20 nm AgNPs were found to have the highest surface enhancement factors (SEFs) in pre-resonance and single molecule resonance (SEFS of 2.1 x 10^6 and 2.5 x 10^10), while the 12 nm AgNPs yielded the highest SEFs in resonant conditions (2.0 x 10^6). The TFF procedure was then introduced to a diverse class of undergraduate and graduate students in an Experimental Nanomaterials and Nanoscience course to demonstrate the versatility of the proposed method for both gold nanoparticles and AgNPs, as well as the ease of applicability for use in different research disciplines and settings. Lastly, the 20 nm TFF-obtained AgNPs were employed for the sub-nanomolar biochemical detection of a potent apoptotic metabolite, chelerythrine (CET), in human lens epithelial cell extracts. The TFF-fractionated AgNP colloid allowed for quantification of CET content within several cell compartments via a reproducible calibration curve extending over five orders of magnitude (10^-5 to 10^-10 M in CET concentration). The results of these aims offer strong evidence that TFF can be 1) utilized to yield SERS substrates capable of extending detection limits and increasing spectral signals, 2) easily adapted for a variety of nanoparticle colloids as well as research and industrial settings, and 3) employed to obtain AgNPs that facilitate trace biochemical SERS-based detection even in extensive biological matrices.