Borja Sepúlveda

An integrated optical interferometric nanodevice based on silicon technology for biosensor applications

Integrated optical sensors have become important in recent years since they are the only technology which allows the direct detection of biomolecular interactions. Moreover, silicon microelectronics technology allows mass production as well as the fabrication of nano-/macrosystems on the same platform by hybrid integration of sources, sensors, photodetectors and complementary metal-oxide semiconductor electronics.For the fabrication of an optical sensor nanodevice with an integrated Mach–Zehnder interferometric (MZI) configuration, the optical waveguides must have two main features: monomode behaviour and a high surface sensitivity. In this paper we present the development of a MZI sensor based on total internal reflection waveguides with nanometre dimensions. The aim is to use these sensors in environmental control to detect water pollutants by immunoassay techniques.

Highly sensitive detection of biomolecules with the magneto-optic surface-plasmon-resonance sensor

The characteristics of a novel magneto-optic surface-plasmon-resonance (MOSPR) sensor and its use for the detection of biomolecules are presented. This physical transduction principle is based on the combination of the magneto-optic activity of magnetic materials and a surface-plasmon resonance of metallic layers. Such a combination can produce a sharp enhancement of the magneto-optic effects that strongly depends on the optical properties of the surrounding medium, allowing its use for biosensing applications. Experimental characterizations of the MOSPR sensor have shown an increase in the limit of detection by a factor of 3 in changes of refractive index and in the adsorption of biomolecules compared with standard sensors. Optimization of the metallic layers and the experimental setup could result in an improvement of the limit of detection by as much as 1 order of magnitude.

Trends and challenges of refractometric nanoplasmonic biosensors: a review.

Motivated by potential benefits such as sensor miniaturization, multiplexing opportunities and higher sensitivities, refractometric nanoplasmonic biosensing has profiled itself in a short time span as an interesting alternative to conventional Surface Plasmon Resonance (SPR) biosensors. This latter conventional sensing concept has been subjected during the last decades to strong commercialization, thereby strongly leaning on well-developed thin-film surface chemistry protocols. Not surprisingly, the examples found in literature based on this sensing concept are generally characterized by extensive analytical studies of relevant clinical and diagnostic problems. In contrast, the more novel Localized Surface Plasmon Resonance (LSPR) alternative finds itself in a much earlier, and especially, more fundamental stage of development. Driven by new fabrication methodologies to create nanostructured substrates, published work typically focuses on the novelty of the presented material, its optical properties and its use - generally limited to a proof-of-concept - as a label-free biosensing scheme. Given the different stages of development both SPR and LSPR sensors find themselves in, it becomes apparent that providing a comparative analysis of both concepts is not a trivial task. Nevertheless, in this review we make an effort to provide an overview that illustrates the progress booked in both fields during the last five years. First, we discuss the most relevant advances in SPR biosensing, including interesting analytical applications, together with different strategies that assure improvements in performance, throughput and/or integration. Subsequently, the remaining part of this work focuses on the use of nanoplasmonic sensors for real label-free biosensing applications. First, we discuss the motivation that serves as a driving force behind this research topic, together with a brief summary that comprises the main fabrication methodologies used in this field. Next, the sensing performance of LSPR sensors is examined by analyzing different parameters that can be invoked in order to quantitatively assess their overall sensing performance. Two aspects are highlighted that turn out to be especially important when trying to maximize their sensing performance, being (1) the targeted functionalization of the electromagnetic hotspots of the nanostructures, and (2) overcoming inherent negative influence that stem from the presence of a high refractive index substrate that supports the nanostructures. Next, although few in numbers, an overview is given of the most exhaustive and diagnostically relevant LSPR sensing assays that have been recently reported in literature, followed by examples that exploit inherent LSPR characteristics in order to create highly integrated and high-throughput optical biosensors. Finally, we discuss a series of considerations that, in our opinion, should be addressed in order to bring the realization of a stand-alone LSPR biosensor with competitive levels of sensitivity, robustness and integration (when compared to a conventional SPR sensor) much closer to reality.

Optical biosensor microsystems based on the integration of highly sensitive Mach–Zehnder interferometer devices

We present highly sensitive optical biosensors able to be fully integrated in lab-on-a-chip microsystems using standard CMOS compatible processes. These optical biosensors are based on integrated Mach–Zehnder interferometers, which have been designed to have high surface sensitivity and monomode behaviour. As a biosensing application of the devices we show the real-time detection of the covalent immobilization and hybridization of DNA strands without labelling. In order to achieve a lab-on-a-chip portable microsystem, we present the integration of the sensor with a CMOS compatible microfluidic system using SU-8 photolithography patterned layers.

Identification of the Optimal Spectral Region for Plasmonic and Nanoplasmonic Sensing

We present a theoretical and experimental study involving the sensing characteristics of wavelength-interrogated plasmonic sensors based on surface plasmon polaritons (SPP) in planar gold films and on localized surface plasmon resonances (LSPR) of single gold nanorods. The tunability of both sensing platforms allowed us to analyze their bulk and surface sensing characteristics as a function of the plasmon resonance position. We demonstrate that a general figure of merit (FOM), which is equivalent in wavelength and energy scales, can be employed to mutually compare both sensing schemes. Most interestingly, this FOM has revealed a spectral region for which the surface sensitivity performance of both sensor types is optimized, which we attribute to the intrinsic dielectric properties of plasmonic materials. Additionally, in good agreement with theoretical predictions, we experimentally demonstrate that, although the SPP sensor offers a much better bulk sensitivity, the LSPR sensor shows an approximately 15% better performance for surface sensitivity measurements when its FOM is optimized. However, optimization of the substrate refractive index and the accessibility of the relevant molecules to the nanoparticles can lead to a total 3-fold improvement of the FOM in LSPR sensors.

Integrated Mach-Zehnder interferometer based on ARROW structures for biosensor applications

Abstract The theoretical design, fabrication and characterisation of an evanescent field integrated optical (IO) sensor based on a rib anti-resonant reflecting optical waveguide (ARROW) structure are presented. The optical waveguides are designed to verify two conditions: mono-mode behaviour and high surface sensitivity. The sensor system is fabricated with ‘silicon microelectronics technology’ and it has been tested as a refractometer with glucose solutions of different refractive indices. The feasibility of applying the sensor for immunosensing is shown with antibody/antigen binding experiments.

Magnetooptic effects in surface-plasmon-polaritons slab waveguides

This paper analyzes the magnetooptic (MO) effects in surface plasmon polaritons (SPP) propagating in thin metallic layers as a function of the metal thickness. Two different configurations are analyzed: a ferromagnetic metal surrounded by nonmagnetic dielectrics and a nonmagnetic metal bounded by ferromagnetic dielectrics. Depending on the configuration and the thickness of the metallic layer, waveguides with very low attenuation losses and high MO effects can be obtained. These configurations could be used to design MO active devices in SPP-based optics.

Au/Fe/Au multilayer transducers for magneto-optic surface plasmon resonance sensing

In this paper, we analyze the magnetoplasmonic MP features and sensing capabilities of Au/Fe/Au trilayer structures, as transducers of the magneto-optic surface plasmon resonance MOSPR biosensor. This biosensor, which can surpass the sensitivity of the standard SPR sensor, is based on a MP modulation technique generated by the simultaneous stimulation of the surface plasmon polaritons SPP and the transversal magneto-optical Kerr effect TMOKE. We study the magneto-optical activity of the trilayers as a function of the thickness and position of the Fe layer. We first demonstrate that this kind of structure allows modulating the SPP through an external magnetic field and moreover, induce a strong enhancement of the TMOKE effect. The modulation of the SPP is linearly proportional to the thickness of Fe layer and inversely proportional to the distance between the Fe layer and the external dielectric medium. Finally, we experimentally confirm a twofold increase in the MOSPR sensitivity with respect to the intensity-interrogated SPR biosensor in bulk refractive-index changes, keeping a similar chemical resistance and stability, unprecedented in other MP transducers, and biofunctionalization protocols.

All-optical phase modulation for integrated interferometric biosensors

We present the theoretical and the experimental implementation of an all-optical phase modulation system in integrated Mach-Zehnder Interferometers to solve the drawbacks related to the periodic nature of the interferometric signal. Sensor phase is tuned by modulating the emission wavelength of low-cost commercial laser diodes by changing their output power. FFT deconvolution of the signal allows for direct phase readout, immune to sensitivity variations and to light intensity fluctuations. This simple phase modulation scheme increases the signal-to-noise ratio of the measurements in one order of magnitude, rendering in a sensor with a detection limit of 1.9·10⁻⁷ RIU. The viability of the all-optical modulation approach is demonstrated with an immunoassay detection as a biosensing proof of concept.

Suitable combination of noble/ferromagnetic metal multilayers for enhanced magneto-plasmonic biosensing

We present a theoretical and experimental study on the biosensing sensitivity of Au/Co/Au multilayers as transducers of the magneto-optic surface-plasmon-resonance (MOSPR) sensor. We demonstrate that the sensing response of these magneto-plasmonic (MP) transducers is a trade-off between the optical absorption and the magneto-optical activity, observing that the MP multilayer with larger MO effect does not provide the best sensing response. We show that it is possible to design highly-sensitive MP transducers able to largely surpass the limit of detection of the conventional surface-plasmon-resonance (SPR) sensor. This was proved comparing the biosensing performance of both sensors for the label-free detection of short DNA chains hybridization. For this purpose, we used and tested a novel label-free biofunctionalization protocol based on polyelectrolytes, which increases the resistance of MP transducers in aqueous environments.