Laura M. Lechuga

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.

Development of nanomechanical biosensors for detection of the pesticide DDT.

We report the use of a novel technique for detection of the organochlorine insecticide compound dichlorodiphenyltrichloroethane (DDT) by measuring the nanometer-scale bending of a microcantilever produced by differential surface stress. A synthetic hapten of the pesticide conjugated with bovine serum albumin (BSA) was covalently immobilised on the gold-coated side of the cantilever by using thiol self assembled monolayers. The immobilisation process is characterised by monitoring the cantilever deflection in real-time. Then specific detection is achieved by exposing the cantilever to a solution of a specific monoclonal antibody to the DDT hapten derivative. The specific binding of the antibodies on the cantilever sensitised side is measured with nanomolar sensitivity. Direct detection is proved by performing competitive assays, in which the cantilever is exposed to a mixed solution of the monoclonal antibody and DDT. The future prospects and limitations to be overcome for the application of nanomechanical sensors for pesticide detection are discussed.

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.

Determination of environmental organic pollutants with a portable optical immunosensor

A portable surface plasmon resonance (SPR) optical biosensor device is described as a direct immunosensing system to determine organic pollutants in natural water samples. Monitoring of organochlorine (DDT), organophosphorus (chlorpyrifos) and carbamate (carbaryl) compounds within the concentration levels stipulated by the European legislation, can be accomplished using this immunosensor. The lowest limit of detection (LOD) was obtained for DDT, at 20 ng L(-1), whilst 50 ng L(-1) and 0.9 microg L(-1), were achieved for chlorpyrifos and carbaryl, respectively. Matrix effects were evaluated for the carbaryl immunoassay in different water types with detection limits within the range of carbaryl standard curves in distilled water (0.9-1.4 microg L(-1)). The covalent immobilization of the analyte derivative through an alkanethiol self-assembled monolayer (SAM) allowed the reusability of the sensor surface during more than 250 regeneration cycles. The quality of the regeneration was proved over a 1-month period of continuous working. The analysis time for a complete assay cycle, including regeneration, comprises 24 min. Our portable SPR-sensor system is already a market product, commercialized by the company SENSIA, SL. The size and electronic configuration of the device allow its portability and utilization on real contaminated locations.

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.

The realization of an integrated Mach-Zehnder waveguide immunosensor in silicon technology

We describe the realization of a symmetric integrated channel waveguide Mach-Zehnder sensor which uses the evanescent field to detect small refractive-index changes (?nmin ? 1 × 10?4) near the guiding-layer surface. This guiding layer consists of ridge structures with a height of 3 nm and a width of 4 ?m made in Si3N4. This layer has a thickness of 100 nm. The sensor device has been tested with glucose solutions of different bulk refractive indices. Results of a slab-model calculation are in good agreement with obtained experimental results. The feasibility of applying this sensor for immunosensing, detecting directly the binding of antigen to an antibody receptor surface, 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.