Amanda J. Haes

A Nanoscale Optical Biosensor : The Long Range Distance Dependence of the Localized Surface Plasmon Resonance of Noble Metal Nanoparticles

Silver and gold nanotriangles were fabricated by nanosphere lithography (NSL) and their localized surface plasmon resonance (LSPR) spectra were measured by UV -vis extinction spectroscopy. It is demonstrated that the short range (viz., 0 -2 nm) distance dependence of the electromagnetic fields that surround these nanoparticles when resonantly excited can be systematically tuned by changing their size, structure, and composition. This is accomplished by measuring the shift in the peak wavelength, λmax, of their LSPR spectra caused by the adsorption of hexadecanethiol as a function of nanoparticle size (in-plane width, out-of-plane height, and aspect ratio), shape (truncated tetrahedron versus hemisphere), and composition (silver versus gold). We find that the hexadecanethiol-induced LSPR shift for Ag triangles decreases when in-plane width is increased at fixed out-of-plane height or when height is increased at fixed width. These trends are the opposite to what was seen in an earlier study of the long range distance dependence in which 30 nm thick layers were examined (Haes et al. J. Phys. Chem. B2004, 108, 109), but both the long and short range results are confirmed by a theoretical analysis based on finite element electrodynamics. The theory results also indicate that the short range results are primarily sensitive to hot spots (regions of high induced electric field) near the tips of the triangles, so this provides an example where enhanced local fields play an important role in extinction spectra. Our measurements further show that the hexadecanethiol-induced LSPR peak shift is larger for nanotriangles than for hemispheres with equal volumes and is larger for Ag nanotriangles than for Au nanotriangles with the same in-plane widths and out-of-plane heights. The dependence of the alkanethiolinduced LSPR peak shift on chain length for Ag nanotriangles is approximately size-independent. We anticipate that the improved understanding of the short range dependence of the adsorbate-induced LSPR peak shift on nanoparticle structure and composition reported here will translate to significant improvements in the sensitivity of refractive-index-based nanoparticle nanosensors.

Localized surface plasmon resonance biosensors

In this review, the most recent progress in the development of noble metal nano-optical sensors based on localized surface plasmon resonance (LSPR) spectroscopy is summarized. The sensing principle relies on the LSPR spectral shifts caused by the surrounding dielectric environmental change in a binding event. Nanosphere lithography, an inexpensive and simple nanofabrication technique, has been used to fabricate the nanoparticles as the LSPR sensing platforms. As an example of the biosensing applications, the LSPR detection for a biomarker of Alzheimers disease, amyloid-derived diffusable ligands, in human brain extract and cerebrospinal fluid samples is highlighted. Furthermore, the LSPR sensing method can be modified easily and used in a variety of applications. More specifically, a LSPR chip capable of multiplex sensing, a combined electrochemical and LSPR protocol and a fabrication method of solution-phase nanotriangles are presented here.

Using Solution-Phase Nanoparticles, Surface-Confined Nanoparticle Arrays and Single Nanoparticles as Biological Sensing Platforms

The intense colors of noble metal nanoparticles have inspired artists and fascinated scientists for hundreds of years. In this review, we describe three sensing platforms based on the tunability of the localized surface plasmon resonance (LSPR) of gold and silver nanoparticles. Specifically, the color associated with solution-phase nanoparticles, surface-confined nanoparticle arrays, and single nanoparticles will be shown to be tunable and useful as platforms for biological sensing.

Preliminary studies and potential applications of localized surface plasmon resonance spectroscopy in medical diagnostics

Miniature optical sensors that specifically identify low concentrations of environmental and biological substances are in high demand. Currently, there is no optical sensor that provides identification of the aforementioned species without amplification techniques at naturally occurring concentrations. Recently, it has been demonstrated that triangular silver nanoparticles have remarkable optical properties and that their enhanced sensitivity to their nanoenvironment has been used to develop a new class of optical sensors using localized surface plasmon resonance spectroscopy. The examination of both model and nonmodel biological assays using localized surface plasmon resonance spectroscopy will be presented in this review. It will be demonstrated that the use of a localized surface plasmon resonance nanosensor rivals the sensitivity and selectivity of, and provides a low-cost alternative to, commercially available sensors.

Investigations of the Mechanism of Gold Nanoparticle Stability and Surface Functionalization in Capillary Electrophoresis

Covalently functionalized gold nanoparticles influence capillary electrophoresis separations of neurotransmitters in a concentration- and surface-chemistry-dependent manner. Gold nanoparticles with either primarily covalently functionalized carboxylic acid (Au@COOH) or amine (Au@NH(2)) surface groups are characterized using extinction spectroscopy, transmission electron microscopy, and zeta potential measurements. The impact of the presence of nanoparticles and their surface chemistry is investigated, and at least three nanoparticle-specific mechanisms are found to effect separations. First, the degree of nanoparticle-nanoparticle interactions is quantified using a new parameter termed the critical nanoparticle concentration (CNC). CNC is defined as the lowest concentration of nanoparticles that induces predominant nanoparticle aggregation under specific buffer conditions and is determined using dual-wavelength photodiode array detection. Once the CNC has been exceeded, reproducible separations are no longer observed. Second, nanoparticle-analyte interactions are dictated by electrostatic interactions which depend on the pK(a) of the analyte and surface charge of the nanoparticle. Finally, nanoparticle-capillary interactions occur in a surface-chemistry-dependent manner. Run buffer viscosity is influenced by the formation of a nanoparticle steady-state pseudostationary phase along the capillary wall. Despite differences in buffer viscosity leading to changes in neurotransmitter mobilities, no significant changes in electroosmotic flow were observed. As a result of these three nanoparticle-specific interactions, Au@NH(2) nanoparticles increase the mobility of the neurotransmitters while a smaller opposite effect is observed for Au@COOH nanoparticles. Understanding nanoparticle behavior in the presence of an electric field will have significant impacts in separation science where nanoparticles can serve to improve either the mobility or detection sensitivity of target molecules.

Salt-Mediated Self Assembly of Thioctic Acid on Gold Nanoparticles

Self-assembled monolayer (SAM) modification is a widely used method to improve the functionality and stability of bulk and nanoscale materials. For instance, the chemical compatibility and utility of solution-phase nanoparticles are often improved using covalently bound SAMs. Herein, solution-phase gold nanoparticles are modified with thioctic acid SAMs in the presence and absence of salt. Molecular packing density on the nanoparticle surfaces is estimated using X-ray photoelectron spectroscopy and increases by ∼20% when molecular self-assembly occurs in the presence versus the absence of salt. We hypothesize that as the ionic strength of the solution increases, pinhole and collapsed-site defects in the SAM are more easily accessible as the electrostatic interaction energy between adjacent molecules decreases, thereby facilitating the subsequent assembly of additional thioctic acid molecules. Significantly, increased SAM packing densities increase the stability of functionalized gold nanoparticles by a factor of 2 relative to nanoparticles functionalized in the absence of salt. These results are expected to improve the reproducible functionalization of solution-phase nanomaterials for various applications.

Nanoparticle optics: Sensing with nanoparticle arrays and single nanoparticles

Recently, nanoparticles have become the platform for many sensing schemes. In particular, the utilization of the optical response of nanoparticles to changes in their nanoenvironment has served as a signal transduction mechanism for these sensing events. For example, silver nanoparticle arrays synthesized using nanosphere lithography have served as an ultrasensitive detection platform for small molecules, proteins, and antibodies with the detection limit of 60,000 and less than 25 molecules/nanoparticle for hexadecanethiol and antibodies, respectively. While this approach is low cost and highly portable, one limitation of the array platform is that the signal arises from approximately 1x106 nanoparticles. A method to improve the overall number of molecules detected would be to decrease the number of nanoparticles probed. Recently, single nanoparticle sensing has been accomplished using dark-field microscopy. A 40 nm shift in the localized surface plasmon resonance induced from less than 60,000 small-molecule adsorbates has been monitored from a single Ag nanoparticle. Additionally, streptavidin sensing has also been demonstrated using a single Ag nanoparticle. Detection platforms based on nanoparticle arrays and single nanoparticles will be discussed and compared.Recently, nanoparticles have become the platform for many sensing schemes. In particular, the utilization of the optical response of nanoparticles to changes in their nanoenvironment has served as a signal transduction mechanism for these sensing events. For example, silver nanoparticle arrays synthesized using nanosphere lithography have served as an ultrasensitive detection platform for small molecules, proteins, and antibodies with the detection limit of 60,000 and less than 25 molecules/nanoparticle for hexadecanethiol and antibodies, respectively. While this approach is low cost and highly portable, one limitation of the array platform is that the signal arises from approximately 1x106 nanoparticles. A method to improve the overall number of molecules detected would be to decrease the number of nanoparticles probed. Recently, single nanoparticle sensing has been accomplished using dark-field microscopy. A 40 nm shift in the localized surface plasmon resonance induced from less than 60,000 small-molecule adsorbates has been monitored from a single Ag nanoparticle. Additionally, streptavidin sensing has also been demonstrated using a single Ag nanoparticle. Detection platforms based on nanoparticle arrays and single nanoparticles will be discussed and compared.© (2003) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Probing cells with noble metal nanoparticle aggregates

This review focuses on the integration of noble metal nanoparticle aggregates as tags and transport vessels in cellular applications. The natural tendency of nanoparticles to aggregate can be reduced through surface modification; however, this stabilization is often compromised in the cellular environment. The degree of nanoparticle aggregation has both positive and negative consequences. Nanoparticle aggregates are more efficiently removed by the organism compared with single nanoparticles, preventing delivery to their cellular target. In addition, these aggregates are recognized by cells in different ways versus isolated nanoparticles. Despite these negatives, aggregates exhibit enhancement for many detection and treatment techniques in comparison with single nanoparticles. In coming years, the role of aggregates and better control over the degree of aggregation in cellular studies will be required for the realization of medical applications.

Nanoscale optical biosensors based on localized surface plasmon resonance spectroscopy

The Ag nanoparticle based localized surface plasmon resonance (LSPR) nanosensor yields ultrasensitive biodetection with extremely simple, small, light, robust, and low-cost instrumentation. Using LSPR spectroscopy, the model system, biotinylated surface-confined Ag nanotriangles, was used to detect less than one picomolar up to micromolar concentrations of streptavidin. Additionally, the monitoring of anti-biotin binding to biotinylated Ag nanotriangles exhibited that the system could be used as a solution immunoassay. The system was rigorously tested for nonspecific binding interactions and was found to display virtually no adverse results. These results represent important new steps in the development of the LSPR nanobiosensor for applications in medical diagnostics, biomedical research, and environmental science.

Linear Assembly of Gold Nanoparticle Clusters via Centrifugation

Centrifugation is widely used in the synthesis and handling of solution-phase nanoparticles to improve their purity and to change the composition of the solvent. Herein, we couple the optical properties of citrate-stabilized gold nanoparticles and silica encapsulation to investigate how centrifugation impacts the formation of stabilized nanoparticle clusters in solution without the use of linker molecules or asymmetric functionalization. Gold nanoparticles preconcentrated using a high (9,400) g force result in linear assemblies of gold cores that are spaced by approximately 1-4 nm within Au(n)@SiO(2) structures (n = number of gold nanoparticle cores per silica shell) with approximately 30% monomers, 30% dimers, 20% trimers, and 10% 4-7mers. In comparison, nanoparticles preconcentrated using (stirred) ultrafiltration and low (23) g force centrifugation have statistically identical cluster distributions (90% monomers, 9% dimers, and 1% trimers) whereas nanoparticles that are not preconcentrated always exhibit 100% monomers using the same silica coating procedure. We hypothesize that under high g force, the electrical double layer surrounding the gold nanoparticles is slightly polarized thereby increasing the attraction between nanoparticles and the formation of stable clusters. The conductivity of the solution plays an important role in this stabilization. This novel demonstration of linear cluster formation of gold nanoparticles using centrifugation suggests that this commonly used preparative tool can both positively or negatively impact the fundamental properties of these materials and their use in various applications.