Recent advances in

In this study, we report on ultrasensitive protein detection with lithographically prepared plasmonic nanostructures. We have engineered optical nanosensors by the combined approach of negative resist, electron beam lithography, and reactive ion etching to form highly reproducible arrays of gold dimers in which the near-field coupling in their subwavelength gap enables for scaling the sensing volume down to the single-protein scale. In good agreement with recent theoretical predictions, the dimer geometry offers enhanced sensitivity compared to isolated particles for the detection of both small organic molecules and proteins. Beyond, by exploiting size exclusion, we are capable of monitoring the number of proteins able to bind across the gap region through the precise engineering of the structures coupled to the selective binding of a surface-assembled monolayer and covalent attachment of the protein.

Label-free biosensing based on metallic nanoparticles supporting localized surface plasmon resonances (LSPR) has recently received growing interest (Anker, J. N., et al. Nat. Mater. 2008, 7, 442−453). Besides its competitive sensitivity (Yonzon, C. R., et al. J. Am. Chem. Soc. 2004, 126, 12669−12676; Svendendahl, M., et al. Nano Lett. 2009, 9, 4428−4433) when compared to the surface plasmon resonance (SPR) approach based on extended metal films, LSPR biosensing features a high-end miniaturization potential and a significant reduction of the interrogation device bulkiness, positioning itself as a promising candidate for point-of-care diagnostic and field applications. Here, we present the first, paralleled LSPR lab-on-a-chip realization that goes well beyond the state-of-the-art, by uniting the latest advances in plasmonics, nanofabrication, microfluidics, and surface chemistry. Our system offers parallel, real-time inspection of 32 sensing sites distributed across 8 independent microfluidic channels with very high reproducibility/repeatability. This enables us to test various sensing strategies for the detection of biomolecules. In particular we demonstrate the fast detection of relevant cancer biomarkers (human alpha-feto-protein and prostate specific antigen) down to concentrations of 500 pg/mL in a complex matrix consisting of 50% human serum. KEYWORDS: Plasmonics, LSPR, parallel, biosensing, lab-on-a-chip, cancer T he biosensing community has long been striving for an idealistic device consisting of high sensitivity, specificity, selectivity, and parallel real-time detection, coupled with low production and operational costs. In addition this device should be both environmentally and user-friendly and be portable, robust, and resistant to a wide range of external conditions (temperature, electromagnetic (EM) radiation, humidity), among other things. On the road toward this biosensing "Holy Grail", contemporary technology has been able to deliver numerous classes of biosensors that are focused on a particular application or niche in the biosensing market; however, no such device currently exists that delivers all or most of these requirements. Among these, optical biosensors operating in a label-free format have positioned themselves as very promising candidates owing to the inherent properties of light. Speed, inertness to external interferences, and almost unlimited bandwidth for data transfer has made light a preferred choice of transduction. With the advent of nanotechnology, especially in the field of plasmonics, surface plasmon resonance (SPR) technology revolutionized the biosensing field in the last two decades. The gold standard status of SPR is owed largely to its highly sensitive transducing mechanism. Namely, surface propagating EM waves called surface plasmon polaritons (SPPs) exhibit extraordinary sensitivity to the refractive index interfacial changes at the boundary between metal and dielectric. However, the activation of this transducing mechanism requires rather complex supporti...

We study high-order harmonic generation (HHG) resulting from the illumination of plasmonic nanostructures with a short laser pulse of long wavelength. We demonstrate that both the confinement of the electron motion and the inhomogeneous character of the laser electric field play an important role in the HHG process and lead to a significant increase of the harmonic cutoff. In particular, in bow-tie nanostructures with small gaps, electron trajectories with large excursion amplitudes experience significant confinement and their contribution is essentially suppressed. In order to understand and characterize this feature, we combine the numerical solution of the time-dependent Schrödinger equation (TDSE) with the electric fields obtained from 3D finite element simulations. We employ time-frequency analysis to extract more detailed information from the TDSE results and classical tools to explain the extended harmonic spectra. The spatial inhomogeneity of the laser electric field modifies substantially the electron trajectories and contributes also to cutoff increase.

Noninvasive and ultra-accurate optical manipulation of nanometer objects has recently gained interest as a powerful tool in nanotechnology and biophysics. Self-induced back-action (SIBA) trapping in nano-optical cavities has the unique potential for trapping and manipulating nanometer-sized objects under low optical intensities. However, thus far, the existence of the SIBA effect has been shown only indirectly via its enhanced trapping performances. In this article, we present the first time direct experimental evidence of the self-reconfiguration of the optical potential that is experienced by a nanoparticle trapped in a plasmonic nanocavity. Our observations enable us to gain further understanding of the SIBA mechanism and to determine the optimal conditions for boosting the performances of SIBA-based nano-optical tweezers.