Linda Gunnarsson

Interparticle coupling effects in nanofabricated substrates for surface-enhanced Raman scattering

Surface-enhanced Raman scattering (SERS) substrates, consisting of arrays of electromagnetically coupled Ag nanoparticles on Si, were manufactured by electron-beam lithography. Substrate Raman efficiency, evaluated from the relative SERS intensities of the adsorbates rhodamine 6G and thiophenol, was found to increase rapidly with decreasing interparticle separation, signaling the importance of strong interparticle coupling effects in SERS. The observed SERS efficiency variation can be qualitatively explained in terms of electrostatic models of coupled metal structures.

Ultrahigh sensitivity made simple: nanoplasmonic label-free biosensing with an extremely low limit-of-detection for bacterial and cancer diagnostics

We present a simple and robust scheme for biosensing with an ultralow limit-of-detection down to several pg cm(-2) (or several tens of attomoles cm(-2)) based on optical label-free biodetection with localized surface plasmon resonances. The scheme utilizes cost-effective optical components and comprises a white light source, a properly functionalized sensor surface enclosed in a simple fluidics chip, and a spectral analyzer. The sensor surface is produced by a bottom-up nanofabrication technique with hole mask colloidal lithography. Despite its simplicity, the method is able to reliably detect protein-protein binding events at low picomolar and femtomolar concentrations, which is exemplified by the label-free detection of the extracellular adherence protein (EAP) found on the outer surface of the bacterium Staphylococcus aureus and of prostate-specific antigen (PSA), which is believed to be a prostate cancer marker. These experiments pave the way towards an ultra-sensitive yet compact biodetection platform for point-of-care diagnostics applications.

High-Resolution Microspectroscopy of Plasmonic Nanostructures for Miniaturized Biosensing

In this article, we demonstrate how to perform microscale spectroscopy of plasmonic nanostructures in order to minimize the noise when determining the resonance peak wavelength. This is accomplished using an experimental setup containing standard optical components mounted on an ordinary light microscope. We present a detailed comparison between extinction spectroscopy in transmission mode and scattering spectroscopy under dark field illumination, which shows that extinction measurements provide higher signal-to-noise in almost all situations. Furthermore, it is shown that rational selection of nanostructure, hardware components, and data analysis algorithms enables tracking of the particle plasmon resonance wavelength from a 10 microm x 50 microm area with a resolution of 10(-3) nm in transmission mode. We investigate how the temporal resolution, which can be improved down to 17 ms, affects the noise characteristics. In addition, we show how data can be acquired from an area as small as 2 microm x 10 microm (approximately 240 particles) at the expense of higher noise on longer time scales. In comparison with previous work on macroscopic sensor designs, this represents a sensor miniaturization of 5 orders of magnitude, without any loss in signal-to-noise performance. As a model system, we illustrate biomolecular detection using gold nanodisks prepared by colloidal lithography. The microextinction measurements of nanodisks described here provide detection of protein surface coverages as low as 40 pg/cm(2) (<0.1% of saturated binding). In fact, the miniaturized system provides a detection limit in terms of surface coverage comparable to state of the art macroscopic sensors, while simultaneously being as close to single protein molecule detection as sensors based on a single nanoparticle.

A self-assembled single-electron tunneling transistor

A single-electron tunneling transistor was made by capturing a chemically synthesized gold cluster between two gold electrodes. The transistor had a quasiperiodic modulation of the current–voltage characteristics as a function of a gate voltage applied to an oxidized aluminum electrode at 4.2 K. The Coulomb blockade voltage for this device was 50 mV observed at 4.2 K and room temperature. The maximum observed blockade voltage was 200 mV for devices without gate.

Optimizing nanofabricated substrates for Surface Enhanced Raman Scattering

Recently, Surface Enhanced Raman Scattering (SERS) has been used to record vibrational spectra from individual molecules adsorbed on colloidal silver particles. For specific panicle dimensions an enormous enhancement, by a factor of 1014, was achieved. In this work we intend to investigate the size and geometry dependence of the SERS effect on supported particles, by manufacturing artificial structures by modern nanofabrication techniques. Arrays of 100–200 nm silver particles of different shapes were prepared on a Si wafer by electron beam lithography, and were characterized by scanning electron microscopy. Preliminary Raman scattering experiments were performed with Rhodamin 6G (R6G) as a test molecule. Enhancement of the Raman signal was observed on all nanofabricated silver patterns, compared to the signals on a uniform silver film or on the (oxidized) Si surface.

Phase-sensitive near-field imaging of metal nanoparticles

In this article we show how the relative phase-shift f can be qualitatively visualized using an aperture NSOM. Single silver nanoparticles or small particle clusters are imaged as circular interference patterns, with the relative intensity of the central peak varying with f. Although the spatial resolution is much worse than what can be obtained in a s-NSOM setup, the advantages are that the present technique can be easily adapted to surface-enhanced spectroscopy measurements of individual nanoparticles or clusters and that the contrast mechanism is relatively simple.

Uptake of gold nanoparticles in healthy and tumor cells visualized by nonlinear optical microscopy

Understanding the mechanism underlying the interactions between inorganic nanostructures and biological systems is crucial for several rapidly growing fields that rely on nano-bio interactions. In particular, the further development of cell-targeted drug delivery using metallic nanoparticles (NP) requires new tools for understanding the mechanisms triggered by the contact of NPs with membranes in different cells at the subcellular level. Here we present a novel concept of multimodal microscopy, enabling three-dimensional imaging of the distribution of gold NPs in living, unlabeled cells. Our approach combines multiphoton induced luminescence (MIL) with coherent anti-Stokes Raman scattering (CARS) microscopy. Comparison with transmission electron microscopy (TEM) reveals in vivo sensitivity down to the single nanostructure. By monitoring the incorporation of NPs in human healthy epidermal keratinocytes and squamous carcinoma cells (SCC), we address the feasibility of noninvasive delivery of NPs for therapeutic purposes. While neutralizing PEG coating was confirmed to prevent NP integration in SCCs, an unexpectedly efficient integration of NPs into keratinocytes was observed. These results, independently validated using TEM, demonstrate the need for advanced surface modification protocols to obtain tumor selectivity for NP delivery. The CARS/MIL microscopy platform presented here is thus a promising tool for noninvasive study of the interaction between NPs and cell.

Interparticle coupling effects in surface-enhanced Raman scattering

We report experimental and theoretical results on the effect of electromagnetic coupling between metal particles in surface-enhanced Raman scattering (SERS). Model calculations of the near-field optical properties of Ag and Au nanoparticle-aggregates show that the electromagnetic surface-enhancement factor can reach 11 orders-of-magnitude in gaps between nearly touching particles. Single particles exhibit a much weaker enhancement, unless the particles contain extremely sharp surface protrusions. Data on spectral fluctuations in single-molecule SERS and measurements on the efficiency of nanofabricated SERS substrates give experimental support for the idea that an efficient interparticle coupling is a necessary requirement for an ultra-high surface-enhancement. We suggest a route for biorecognition induced coupling of metal particles for use in biosensing applications.

Nanofabrication of Self-assembled Molecular-scale Electronics

Single electron tunneling devices were made by combiningstandard electron beam lithography and the self-assembly ofchemically synthesized gold clusters. These clusters, withdiameters from 2 to 5 nm, were captured in a 5–10 nm gapbetween two gold electrodes. The gold particles as well as theelectrodes were covered with self-assembled monolayers (SAM)of organic molecules which served as tunnel barriers.Operating devices show a suppressed current due to the Coulombblockade of tunneling at room temperature. When cooled to4.2 K, a Coulomb staircase was observed. By applying a voltageto an oxidized aluminum gate beneath the electrodes and thetrapped gold cluster the current voltage characteristics weremodulated. Anomalous effects are observed such as constantcurrent plateaus whose positions are gate-voltage dependent.An electrodeposition method for gold has been used tofabricate gaps between electrodes smaller than 2 nm. A self-assembled monolayer was used successfully on the electrodes inorder to prevent the gold atoms from migrating on the surfacebetween the electrodes and thereby short-circuiting thejunction. The conductance of such a tunnel junction has beenmeasured and compared to the theory with good agreement. Fromthis comparison the capacitance of the junction was estimated,and we could use that value to calculate a rough estimation ofthe distance between the electrodes.

Metal nanoparticles amplify photodynamic effect on skin cells in vitro

We report on an investigation aimed to increase the efficiency of photodynamic therapy (PDT) through the influence of localized surface plasmon resonances (LSPRs) in metal nanoparticles. PDT is based on photosensitizers that generate singlet oxygen at the tumour site upon exposure to visible light. Although PDT is a well-established treatment for skin cancer, a major drawback is the low quantum yield for singlet-oxygen production. This motivates the development of novel methods that enhance singlet oxygen generation during treatment. In this context, we study the photodynamic effect on cultured human skin cells in the presence or absence of gold nanoparticles with well established LSPR and field-enhancement properties. The cultured skin cells were exposed to protoporphyrin IX and gold nanoparticles and subsequently illuminated with red light. We investigated the differences in cell viability by tuning different parameters, such as incubation time and light dose. In order to find optimal parameters for specific targeting of tumour cells, we compared normal human epidermal keratinocytes with a human squamous skin cancer cell line. The study indicates significantly enhanced cell death in the presence of nanoparticles and important differences in treatment efficiency between normal and tumour cells. These results are thus promising and clearly motivate further development of nanoparticle enhanced clinical PDT treatment.