Label-free Optical Biosensing on a single chip.

Combining semiconductor technology with photonics, optics, and biochemistry leads to sensors with improved biomedical diagnostic capability

Optimization of interferometric photonic cells for biochemical sensing based on advanced high sensitivity optical techniques

The integration between micro-nano fluidics and optics is a new emerging research field, with promising high impact applications in the area of optical biosensing devices. This is the case of tunable Mach-Zehnder interferometers, photonic crystals and ring resonators, which have been demonstrated recently. Recent investigations1 have demonstrated that by combination of the simultaneous used of Ellipsometry, Reflectometry and Spectrometry based technologies broadly used in semiconductor industry at sub-micron spot-size level and advanced photonic structures, a relevant improvement can be achieved at the level of performance of the current state of the art for label-free biosensing and nano-fluidics metrology. The variation in the effective index of refraction can be easily detected in micron/sub-micron domains due to the fact of using several reflectivity profiles and optical responses simultaneously, making possible to remove ambiguities in the sensing interrogation process. To achieve this novel bio-chemical sensing system, it is proposed to combine the miniaturization of sub-micro-holes based Interferometric photonic structures in combination with sub-micron spot size advance optical techniques holistically. Thus, optical sensing system is based on the observation of external reflectivity profile of the high sensitive photonic structures. The reflectivity profile provides four magnitudes which can be used to assess the photonic structures response. These are the reflected amplitude and phase of the electric field components polarized parallel (p) and perpendicular (s) to the plane incidence. The reflected light of the photonic structures produce spectra interference patterns as a function of the angle of incidence for p and s polarization directions and as a function of the spectral range. These patterns are the fundamental source of information to detect the biomolecules binding in the sensing surfaces, ultra small fraction of volumes and flow control in sub-micron domains. Theoretical calculations at CLUPM demonstrate that a detection limit of 10-7 R.I.U. and surface concentration detection limit of 0.1 pg/mm2 are feasible

Analysis of plasma thermal surface effects on the residual stress field induced by LSP in Al2024-t351

In Laser Shock Processing (LSP) a high intensity pulsed laser beam is focused at the interface between a metallic target and a transparent confining material (normally water) that induces a residual stress distribution in the target material. Without a protective coating thermal effects are present near the target surface. A calculational model has been developed, able to systematically study LSP processes, starting from laser-plasma interaction and coupled thermo-mechanical target behavior. We present results obtained in LSP treatments without coating. In particular the relative influence of thermal/mechanical effects shows that: each effect has a different temporal scale and thermal effects are limited to a small region near the surface; repeated pulses increase maximum compressive residual stress and the depth of the compressive residual stress region; compressive residual stresses very close to the surface level can be induced even without any protective coating through the application of adjacent pulses

Metrología óptica dimensional submicrométrica para determinación de espesores en sub-micro estructuras

En este trabajo se presenta el análisis de una técnica de metrología óptica utilizada para el control de procesos en línea en la fabricación de microchips. Se obtienen los perfiles de reflectividad en función del ángulo de incidencia para una longitud de onda de 675 nm, para los estados de polarización s y p. Se obtiene un modelo teórico para una estructura multicapa, con la que se pueden calcular de forma sencilla las propiedades ópticas y dimensiones de las capas. Se obtiene la incertidumbre de la técnica de medida.-In this work is presented the analysis of a technique of optical metrology widely used in controlling on- line process in fabrication of microchips. Reflectivity profiles as a function of angle of incidence are obtained for a wavelength of 675 nm. A theoretical model for a Si/ SiO2 multilayer stack is also obtained, which can be used to calculate both the thickness and the optical properties of the layers. A calculation of the uncertainty for the measurement technique is also performed

Integrated slot-waveguide microresonator for biochemical sensing

A novel integrated biochemical sensor based on a slot-waveguide [1] microring resonator is demonstrated. The microresonator is fabricated on a Si3N4/SiO2 material platform [2] by using conventional microfabrication techniques, such as Si thermal oxidation, chemical vapour deposition, electron-beam lithography and reactive ion etching. The sensor consists of a 70-μm-radius ring resonator formed by a slot-waveguide [1] having a slot-width of 200 nm. The operation wavelength is 1.3 μm. The device is exposed to different water-ethanol solutions and its transmission spectrum is measured. A linear shift of the resonant wavelength with increasing ambient refractive index of 212 nm/refractive index units (RIU) is observed. This value is more than twice larger than those of strip-waveguide ring resonator biochemical sensors, indicating that higher analyte-probe light interaction occurs in our slot-waveguide sensor as compared to those based on conventional strip waveguides. The sensor detects a minimal refractive index variation of 2x10-4 RIU, limited by the wavelength resolution of the light source (50 pm). Simulations indicate that the slot region is partially filled when the sensor is exposed to an aqueous solution. We also demonstrate the capability of our sensor to measure higher index fluids such as isopropanol (n=1.37) and cyclohexane (n=1.42)

Vertical resonant microcativites based on pillars analyzed by beam profile ellipsometry and reflectometry

A biosensor design is presented by a combination of ellipsometry, reflectometry and spectrometry based techniques is presented. It consists of a lattice of columns forming resonant microcavities. Calculations for reflectivity profiles are shown, and estimations for detection limit in refractive index units are obtained

Characterization of the Performance of Optical Label-Free Biosensors

The field of optical label free biosensors has become a topic of interest during past years, with devices based on the detection of angular or wavelength shift of optical modes [1]. Common parameters to characterize their performance are the Limit of Detection (LOD, defined as the minimum change of refractive index upon the sensing surface that the device is able to detect, and also BioLOD, which represents the minimum amount of target analyte accurately resolved by the system; with units of concentration (common un its are p pm, ng/ml, or nM). LOD gives a first value to compare different biosensors, and is obtained both theoretically (using photonic calculation tools), and experimentally,covering the sensing area with fluids of different refractive indexes

Biosensing comparison between different geometries based on vertical submicron-structrures made of SU-8 resist

Previous work of the research group [1-4] demonstrated the viability of using periodic lattices of micro and nanopillars, called Bio-photonic sensing Cells (BICELLs), as an optical biosensor vertically characterized by visible spectrometry. Also we have studied theoretically [5] the performance of the BICELLs by 2D and 3D simulation in orde r to optimize the biosensing response. In this work we present the fabrication and biosensing comparison of different geometrical parameters on periodic lattices of pillars in order to discuss theoretical conclusions with these results. In this way, we have explored the biosensing response of other patter ns such as crosses, stars, cylinders, concentrical cylinders (Figure 1). Also we introduced a novel method to test the BICELLs in a cost-effective way by using an ultra-thin film of SU-8 spin-coated onto the patterns to reproduce the effect of a biofilm attached to the biosensor surface. Finally we have tested the biosensing response of the different geometries by the well-known Bovine Serum Albumin (BSA) immunoassay and compared with the theoretical simulation

Optimization of Dengue immunoassay by label-free interferometric optical detection method

In this communication we report a direct immunoassay for detecting dengue virus by means of a label-free interferometric optical detection method. We also demonstrate how we can optimize this sensing response by adding a blocking step able to significantly enhance the optical sensing response. The blocking reagent used for this optimization is a dry milk diluted in phosphate buffered saline. The recognition curve of dengue virus over the proposed surface sensor demonstrates the capacity of this method to be applied in Point of Care technology

Towards In-Vitro Point of Care devices for in-situ diagnosis

Electronic and optoelectronic systems and subsystems play an important role to develop In-Vitro Diagnostics (IVDs) systems for healthcare, clinical, agro-food, environmental, pharmaceutical research or drug control, among many other applications. Although significant advantages have been described for label-free biosensing technology, still a limitednumber of compact devices for monitoring IVD in-situ have been already developed. In this paper a discussion about the current trends for developing Point-of-Care devices will be analyzed, as well as the future challenges for in-situ In-vitro diagnostic systems