Label-free Optical Biosensing on a single chip.

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

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

Microfabrication processes for microfluidic devices on a single laser Workstation: direct writing lithography on SU-8, laser ablation on polymers and mask manufacturing

We demonstrate the capability of a laser micromachining workstation for cost-effective manufacturing of a variety of microfluidic devices, including SU-8 microchannels on silicon wafers and 3D complex structures made on polyimide Kapton® or poly carbonate (PC). The workstation combines a KrF excimer laser at 248 nm and a Nd3+:YVO4 DPSS with a frequency tripled at 355 nm with a lens magnification 10X, both lasers working at a pulsed regime with nanoseconds (ns) pulse duration. Workstation also includes a high-resolution motorized XYZ-tilt axis (~ 1 um / axis) and a Through The Lens (TTL) imaging system for a high accurate positioning over a 120 x 120 mm working area. We have surveyed different fabrication techniques: direct writing lithography,mask manufacturing for contact lithography and polymer laser ablation for complex 3D devices, achieving width channels down to 13μ m on 50μ m SU-8 thickness using direct writing lithography, and width channels of 40 μm for polyimide on SiO2 plate. Finally, we have tested the use of some devices for capillary chips measuring the flow speed for liquids with different viscosities. As a result, we have characterized the presence of liquid in the channel by interferometric microscopy

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

Incertidumbre en bio-sensores ópticos asociada al desplazamiento espectral de los modos de interferencia de la señal de transducción

El análisis del comportamiento de los modos de interferencia tiene una aplicación cada vez mas amplia, especialmente en el campo de los biosensores opticos. En este tipo de sensores se observa el desplazamiento Δν de los modos de interferencia de la señal de transducción al reconocer un determinado agente biologico. Para medir ese desplazamiento se debe detectar la posición de un máximo o minimo de la senal antes y después de dicho desplazamiento. En este tipo de biosensores un parámetro de gran importancia es el periodo Pν de la senal el cual es inversamente proporcional al espesor óptico h0 del sensor en ausencia de agente biologico. El aumento de dicho periodo mejora la sensibilidad del sensor pero parece dificultar la detección del minimo o maximo. Por tanto, su efecto sobre la incetidumbre del resultado de la medida presentados efectos contrapuestos: la mejora de la sensibilidad frente a la dificultad creciente en la detección del minimo o maximo. En este trabajo, los autores analizan la propagación de incertidumbres en estos sensores utilizando herramientas de ajuste por MM.CC. para la detección de los minimos o máximos de la senal y técnicas de propagación de incertidumbres descritas en los suplementos 2 de la Guia ISO-GUM. El resultado del análisis permite dar una respuesta, justificada desde el punto de vista metrologico, de en que condiciones es conveniente o no aumentar el periodo Pν de la senal

Label-free biosensing for dry eye by Means of BICELLS

The use of Biophotonic Sensing Cells (BICELLs) based on micro-nano pattemed photonic architectures has been recently proven as an efficient methodology for label-free biosensing by using Optical Interrogation [1]. According to this, we have studied the different optical response for a specific typology of BICELL, consisting of structures of SU -8. This material is biocompatible with different types of biomolecules and can be immobilized on its sensing surface. In particular, we have measured the optical response for a biomarker in clinic diagnostic of dry eye. Although different proteins can be enstudied such as: PRDX5, ANXA 1, ANXA 11, CST 4, PLAA Y S 1 OOA6 related with ocular surface (dry eye), for this work PLAA (phospholipase A2) is studied by means of label free biosensing based on BICELLs for analyzing the performance and specificity according with means values of concentration in ROC curves

Biophotonic Sensing Cells (BICELLs) for label-free biosensing

Label free immunoassay sector is a ferment of activity, experiencing rapid growth as new technologies come forward and achieve acceptance. The landscape is changing in a “bottom up” approach, as individual companies promote individual technologies and find a market for them. Therefore, each of the companies operating in the label-free immunoassay sector offers a technology that is in some way unique and proprietary. However, no many technologies based on Label-free technology are currently in the market for PoC and High Throughput Screening (HTS), where mature labeled technologies have taken the market

Silicon nanopillar arrays with SiO2 overlayer for biosensing application

We present the fabrication of silicon dioxide (SiO2) coated silicon nanopillar array structures and demonstrate their application as sensitive optical biosensors. Colloidal lithography, plasma dry etching and deposition processes are used to fabricate SiO2 coated Si nanopillar arrays with two different diameters and periods. Proof of concept bio recognition experiments are carried out with the bovine serum albumin (BSA)/antiBSA model system using Fourier transform visible and IR spectrometry (FT-VIS-IR) in reflection mode. A limit of detection (LoD) value of 5.2 ng/ml is estimated taking in to account the wavenumber uncertainty in the measurements