An important motivation of the actual biosensor research is to develop a multiplexed sensing platform of high sensitivity fabricated with large-scale and low-cost technologies for applications such as diagnosis and monitoring of diseases, drug discovery and environmental control. Biosensors based on localized plasmon resonance (LSPR) have demonstrated to be a novel and effective platform for quantitative detection of biological and chemical analytes. Here, we describe a novel label-free nanobiosensor consisting of an array of closely spaced, vertical, elastomeric nanopillars capped with plasmonic gold nanodisks in a SU-8 channel. The principle is based on the refractive index sensing using the LSPR of gold nanodisks. The fabrication of the nanobiosensor is based on replica molding technique and gold nanodisks are incorporated on the polymer structures by e-beam evaporation. In this work, we provide the strategies for controlling the silicon nanostructure replication using thermal polymers and photopolymers with different Young's modulus, in order to minimize the common distortions in the process and to obtain a reliable replica of the Si master. The master mold of the biosensor consists of a hexagonal array of silicon nanopillars, whose diameter is ~200 nm, and whose height can range from 250 nm to 1.300 μm, separated 400 nm from the center to center, integrated in a SU-8 microfluidic channel.
In this work we summarize the main results obtained with the portable surface plasmon resonance (SPR) device
developed in our group (commercialised by SENSIA, SL, Spain), highlighting its applicability for the real-time detection
of extremely low concentrations of toxic pesticides in environmental water samples. In addition, we show applications in
clinical diagnosis as, on the one hand, the real-time and label-free detection of DNA hybridization and single point
mutations at the gene BRCA-1, related to the predisposition in women to develop an inherited breast cancer and, on the
other hand, the analysis of protein biomarkers in biological samples (urine, serum) for early detection of diseases.
Despite the large number of applications already proven, the SPR technology has two main drawbacks: (i) not enough
sensitivity for some specific applications (where pM-fM or single-molecule detection are needed) (ii) low multiplexing
capabilities. In order solve such drawbacks, we work in several alternative configurations as the Magneto-optical Surface
Plasmon Resonance sensor (MOSPR) based on a combination of magnetooptical and ferromagnetic materials, to
improve the SPR sensitivity, or the Localized Surface Plasmon Resonance (LSPR) based on nanostructures
(nanoparticles, nanoholes,...), for higher multiplexing capabilities.
We show the design, fabrication and testing of micro/nanobiosensor devices based on optical waveguides in a highly sensitive interferometric configuration and by using evanescent wave detection. The devices are fabricated by standard Silicon CMOS microelectronics technology after a precise design for achieving a high sensitivity for biosensing applications. Two integrated Mach-Zehnder interferometric (MZI) devices, using two technologies, have been developed: (a) a MZI Microdevice based on ARROW waveguide (b) a MZI Nanodevice based on TIR waveguide. Direct biosensing with both sensors has been tested, after a specific receptor coupling to the surface device using nanometer scale immobilization techniques. Further integration of the microoptical sensors, the microfluidics, the photodetectors and the CMOS electronics will render in a lab-on-a-chip microsystem.
Biological and chemical sensing is one of the application fields where integrated optical nanodevices can play an important role . We present a Silicon Integrated Mach-Zehnder Interferometer Nanodevice using a Total Internal Refraction waveguide configuration. The induced changes due to a biomolecular interactions in the effective refractive index of the waveguide,is monitored by the measurement of the change in the properties of the propagating light. For using this device as a biosensor, the waveguides of the structure must verify two conditions: work in the monomode regime and to have a Surface Sensivity as high as possible in the sensing arm. The MZI device structure is: (i) a Si wafer with a 500 mm thickness (ii) a 2 mm thick thermal Silicon-Oxide layer with a refractive index of 1.46 (iii) a LPCVD Silicon Nitride layer of 100 nm thickness and a refractive index of 2.00, which is used as the guiding layer. To achieve monomode behavior is needed to define a rib structure, with a depth of only 3 nm, on the Silicon Nitride layer by a lithographic step. This rib structure is performed by RIE and is the most critical step in the microfabrication of the device. Over the structure a protective layer of LPCVD SiO<sub>2</sub> is deposited, with a 2 mm thickness and a refractive index of 1.46, which is patterned (photolithography) and etched (RIE) to define the sensing arm. The high sensivity of these devices makes them quite suitable for biosensing applications. For that, without loosing their activity the receptors biomolecules are covanlently immobilized, at nanometer scale , on the sensor area surface. Biospecific molecular recognition takes places when the complementary analyte to the receptor is flowed over the receptor using a flow system. Several biosensing applications have been performed with this device as enviromental pollutant control, immunosensing or genetic detection.