High sensitivity biosensors based on shear mode AIN resonators for in liquid operation

El diagnóstico y detección temprana de enfermedades son clave para reducir la tasa de mortalidad, las hospitalizaciones de larga duración y el desaprovechamiento de recursos. En los últimos años se ha impulsado, mediante un aumento de la financiación, el desarrollo de nuevos biosensores de bajo coste capaces de detectar y cuantificar cantidades muy pequeñas de especies biológicas de una forma barata y sencilla. El trabajo presentado en esta Tesis Doctoral describe la investigación llevada a cabo en el desarrollo de sensores gravimétricos basados en resonadores de ondas acústicas de volumen (BAW) de estructura maciza (SMR). Los dispositivos emplean películas delgadas de A1N como material piezoeléctrico y operan en modo de cizalladura, para así poder detectar especies biológicas en medio líquido. El principio de funcionamiento de estos sensores se basa en la variación que experimenta la frecuencia de resonancia al quedar una pequeña masa adherida a su superficie. Necesitan operar en modo de cizalladura para que su resonancia no se atenúe al trabajar en medio líquido, así como ofrecer una superficie capaz de ser funcionalizada específicamente para la especie biológica a detectar. El reto planteado en esta tesis requiere un acercamiento pluridisciplinar al problema que incluye el estudio de los diferentes materiales que constituyen la estructura multicapa que forma un SMR, el diseño y fabricación del dispositivo y del sistema de fluídica, la funcionalización bioquímica de la superficie del sensor, la demostración de la capacidad de detección de especies biológicas y finalmente el diseño y fabricación de la electrónica asociada para la detección de la señal eléctrica. Todas esas tareas han sido abordadas en las distintas etapas del desarrollo de esta tesis y las contribuciones más relevantes se describen en el documento. En el campo de desarrollo de los materiales, se propone un proceso en dos etapas para la pulverización reactiva de capas de A1N que contengan microcristales inclinados capaces de excitar el modo de cizalladura. Se caracteriza la velocidad acústica del modo de cizalladura en todos los materiales que componen la estructura, con el fin de poder obtener un diseño más adecuado del reflector acústico. Se propone un nuevo tipo de material aislante de alta impedancia acústica consistente en capas de W03 pulverizadas que presenta ciertas ventajas tecnológicas frente a las capas convencionales de Ta205. Respecto del diseño del transductor, se estudia la influencia que tienen los con tactos eléctricos extendidos del resonador necesarios para poder adaptar el sistema de fluídica a la estructura. Los resultados indican que es necesario trabajar sobre sustratos aislantes (tanto el soporte como el espejo acústico) para evitar efectos parásitos asociados al uso de capas metálicas bajo los electrodos del resonador que dañan su resonancia. Se analiza la influencia de las diferentes capas del dispositivo en el coeficiente de temperatura de la frecuencia (TCF) del resonador llegando a la conclusión de que las dos últimas capas del reflector acústico afectan significativamente al TCF del SMR, pudiendo reducirse ajusfando adecuadamente sus espesores. De acuerdo con los resultados de estos estudios, se han diseñado finalmente resonadores SMR operando a f .3 GHz en modo de cizalladura, con un área activa de 65000 /xm2, contactos eléctricos que se extienden f .7 mm y factores de calidad en líquido de f 50. Las extensiones eléctricas permiten adaptar el resonador a un sistema de fluídica de metacrilato. Para la detección de especies biológicas se realiza un montaje experimental que permite circular 800 ¡A por la superficie del sensor a través de un circuito cerrado que trabaja a volumen constante. La circulación de soluciones iónicas sobre el sensor descubierto pone de manifiesto que las altas frecuencias de operación previenen los cortocircuitos y por tanto el aislamiento de los electrodos es prescindible. Se desarrolla un protocolo ad-hoc de funcionalización basado en el proceso estándar APTESGlutaraldehído. Se proponen dos alternativas novedosas para la funcionalización de las áreas activas del sensor basadas en el uso de capas de oxidación de Ir02 y su activación a través de un plasma de oxígeno que no daña al dispositivo. Ambos procesos contribuyen a simplificar notablemente la funcionalización de los sensores gravimétricos. Se utilizan anticuerpos y aptámeros como receptores para detectar trombina, anticuerpo monoclonal IgG de ratón y bacteria sonicadas. Una calibración preliminar del sensor con depósitos de capas finas de Si02 de densidad y espesor conocidos permite obtener una sensibilidad de 1800 kHz/pg-cm2 y un límite de detección of 4.2 pg. Finalmente se propone el prototipo de un circuito electrónico de excitación y lectura de bajo coste diseñado empleando teoría de circuitos de microondas. Aunque su diseño y funcionamiento admite mejoras, constituye la última etapa de un sistema completo de bajo coste para el diagnóstico de especies biológicas basado en resonadores SMR de A1N. ABSTRACT Early diagnosis and detection of diseases are essential for reducing mortality rate and preventing long-term hospitalization and waste of resources. These requirements have boosted the efforts and funding on the research of accurate and reliable means for detection and quantification of biological species, also known as biosensors. The work presented in this thesis describes the development and fabrication of gravimetric biosensors based on piezoelectric AlN bulk acoustic wave (BAW) solidly mounted resonators (SMRs) for detection of biological species in liquid media. These type of devices base their sensing principles in the variation that their resonant frequency suffers when a mass is attached to their surface. They need to operate in the shear mode to maintain a strong resonance in liquid and an adequate functionalisation of their sensing area to guarantee that only the targeted molecules cause the shift. The challenges that need to be overcome to achieve piezoelectric BAW resonators for high sensitivity detection in fluids require a multidisciplinary approach, that include the study of the materials involved, the design of the device and the fluidic system, the biochemical functionalisation of the active area, the experimental proof-of-concept with different target species and the design of an electronic readout circuit. All this tasks have been tackled at different stages of the thesis and the relevant contributions are described in the document. In the field of materials, a two-stage sputtering deposition process has been developed to obtain good-quality AlN films with uniformly tilted grains required to excite the shear mode. The shear acoustic velocities of the materials composing the acoustic reflector have been accurately studied to ensure an optimum design of the reflector stack. WO3 sputtered films have been proposed as high acoustic impedance material for insulating acoustic reflectors. They display several technological advantages for the processing of the resonators. Regarding the design, a study of the influence of the electrical extensions necessary to fit a fluidic system on the performance of the devices has been performed. The results indicate that high resistivity substrates and insulating reflectors are necessary to avoid the hindering of the resonance due to the parasitic effects induced by the extensions. The influence of the different layers of the stack on the resultant TCF of the SMRs has also been investigated. The two layers of the reflector closer to the piezoelectric layer have a significant influence on the TCF, which can be reduced by modifying their thicknesses accordingly. The data provided by these studies has led to the final design of the devices, which operate at 1.3 GHz in the shear mode and display an active area of 65000 /xm2 and electrical extensions of 1.7 mm while keeping a Qahear=150 in liquid. The extensions enable to fit a custom-made fluidic system made of methacrylate. To perform the biosensing experiments, an experimental setup with a liquid closed circuit operating at constant flow has been developed. Buffers of ionic characteristics have been tested on non-isolated devices, revealing that high operation frequencies prevent the risk of short circuit. An ad-hoc functionalisation protocol based on the standard APTES - Glutaraldehyde process has been developed. It includes two new processes that simplify the fabrication of the transducers: the use of IrO2 as oxidation layer and its functionalisation through an O2 plasma treatment that does not damage the resonators. Both antibodies and aptamers are used as receptors. In liquid sensing proof-of-concept experiments with thrombin, IgG mouse monoclonal antibody and sonicated bacteria have been displayed. A preliminary calibration of the devices using SiO2 layers reveals a sensitivity of 1800 kHz/pg-cm2 and a limit of detection of 4.2 pg. Finally, a first prototype of a low-cost electronic readout circuit designed using a standard microwave approach has been developed. Although its performance can be significantly improved, it is an effective first approach to the final stage of a portable low-cost diagnostic system based on shear mode AlN SMRs.

In-fibre directional transverse loading sensor based on excessively tilted fibre Bragg gratings

We report a distinctive polarization mode coupling behaviour of tilted fibre Bragg gratings (TFBGs) with a tilted angle exceeding 45°. The ex-45° TFBGs exhibit pronounced polarization mode splitting resulted from the birefringence induced by the grating structure asymmetry. We have fabricated TFBGs with a tilted structure at 81° and studied their properties under transverse load applied to their equivalent fast and slow axes. The results show that the light coupling to the orthogonally polarized modes of the 81°-TFBGs changes only when the load is applied to their slow axis, giving a prominent directional loading response. For the view of real applications, we further investigated the possibility of interrogating such a TFBG-based load sensor using low-cost and compact-size single wavelength source and power detector. The experimental results clearly show that the 81°-TFBGs plus the proposed power-measurement interrogation scheme may be developed to an optical fibre vector sensor system capable of not just measuring the magnitude but also recognizing the direction of the applied transverse load. Using such an 81°-TFBG based load sensor, a load change as small as 1.6 × 10-2 g may be detected by employing a standard photodiode detector.

Resonant cavity Fibre Bragg grating sensor interrogation

This thesis presents a novel high-performance approach to time-division-multiplexing (TDM) fibre Bragg grating (FBG) optical sensors, known as the resonant cavity architecture. A background theory of FBG optical sensing includes several techniques for multiplexing sensors. The limitations of current wavelength-division-multiplexing (WDM) schemes are contrasted against the technological and commercial advantage of TDM. The author’s hypothesis that ‘it should be possible to achieve TDM FBG sensor interrogation using an electrically switched semiconductor optical amplifier (SOA)’ is then explained. Research and development of a commercially viable optical sensor interrogator based on the resonant cavity architecture forms the remainder of this thesis. A fully programmable SOA drive system allows interrogation of sensor arrays 10km long with a spatial resolution of 8cm and a variable gain system provides dynamic compensation for fluctuating system losses. Ratiometric filter- and diffractive-element spectrometer-based wavelength measurement systems are developed and analysed for different commercial applications. The ratiometric design provides a low-cost solution that has picometre resolution and low noise using 4% reflective sensors, but is less tolerant to variation in system loss. The spectrometer design is more expensive, but delivers exceptional performance with picometre resolution, low noise and tolerance to 13dB system loss variation. Finally, this thesis details the interrogator’s peripheral components, its compliance for operation in harsh industrial environments and several examples of commercial applications where it has been deployed. Applications include laboratory instruments, temperature monitoring systems for oil production, dynamic control for wind-energy and battery powered, self-contained sub-sea strain monitoring.

A strain sensing system using a novel optical fibre Bragg grating sensor and a synthetic heterodyne interrogation technique

A potential low cost novel sensing scheme for monitoring absolute strain is demonstrated. The scheme utilizes a synthetic heterodyne interrogation technique working in conjunction with a linearly chirped, sinusoidally tapered, apodized Bragg grating sensor. The interrogation technique is relatively simple to implement in terms of the required optics and the peripheral electronics. This scheme generates an output signal that has a quasi-linear response to absolute strain with a static strain resolution of ~±20 με and an operating range of ~1000 με.

In-fibre twist sensor based on a fibre Bragg grating with 81º tilted structure

We report a strong polarization dependent coupling behavior of fiber Bragg gratings with excessively tilted structures up to 81 . This unique property has been utilized to implement a novel twist sensor, showing high torsion sensitivity. The twist induced light coupling interchange between the two birefringence modes makes it possible to interrogate such a sensor using low-cost intensity demodulation technique.

Fibre optic sensors for high speed hypervelocity impact studies and low velocity drop tests

The initial aim of this project was to develop a non-contact fibre optic based displacement sensor to operate in the harsh environment of a 'Light Gas Gun' (LGG), which can 'fire' small particles at velocities ranging from 1-8.4 km/s. The LGG is used extensively for research in aerospace to analyze the effects of high speed impacts on materials. Ideally the measurement should be made close to the centre of the impact to minimise corruption of the data from edge effects and survive the impact. A further requirement is that it should operate at a stand-off distance of ~ 8cm. For these reasons we chose to develop a pseudo con-focal intensity sensor, which demonstrated resolution comparable with conventional PVDF sensors combined with high survivability and low cost. A second sensor was developed based on 'Fibre Bragg Gratings' (FBG) which although requiring contact with the target the low weight and very small contact area had minimal effect on the dynamics of the target. The FBG was mounted either on the surface of the target or tangentially between a fixed location. The output signals from the FBG were interrogated in time by a new method. Measurements were made on composite and aluminium plates in the LGG and on low speed drop tests. The particle momentum for the drop tests was chosen to be similar to that of the particles used in the LGG.

An area localization scheme for large scale underwater wireless sensor networks

In this paper, we study an area localization problem in large scale Underwater Wireless Sensor Networks (UWSNs). The limited bandwidth, the severely impaired channel and the cost of underwater equipment all makes the underwater localization problem very challenging. Exact localization is very difficult for UWSNs in deep underwater environment. We propose a Mobile DETs based efficient 3D multi-power Area Localization Scheme (3D-MALS) to address the challenging problem. In the proposed scheme, the ideas of 2D multi-power Area Localization Scheme(2D-ALS) [6] and utilizing Detachable Elevator Transceiver (DET) are used to achieve the simplicity, location accuracy, scalability and low cost performances. The DET can rise and down to broadcast its position. And it is assumed that all the underwater nodes underwater have pressure sensors and know their z coordinates. The simulation results show that our proposed scheme is very efficient. © 2009 IEEE.

In-fiber twist sensor based on a fiber Bragg grating with 81° tilted structure

We report a strong polarization dependent coupling behavior of fiber Bragg gratings with excessively tilted structures up to 81°. This unique property has been utilized to implement a novel twist sensor, showing high torsion sensitivity. The twist induced light coupling interchange between the two birefringence modes makes it possible to interrogate such a sensor using low-cost intensity demodulation technique. © 2006 IEEE.

Chirped fibre Bragg grating optical wear sensor

A novel sensor is demonstrated to allow a real-time measurement of the physical wear applied to the surface of an object. Two different measurement methods are presented, both utilizing the reflected power from a sacrificial chirped fibre Bragg grating to give the wear measurement. The measurement systems are simple to implement with the possibility of low cost designs depending on the application. The sensor can measure wear with a resolution of 120 μm. © 2004 IOP Publishing Ltd.

Optical sensor interrogation with a blazed fiber Bragg grating and a charge-coupled device linear array

We present what is to our knowledge the first comprehensive investigation of the use of blazed fiber Bragg gratings (BFBGs) to interrogate wavelength division multiplexed (WDM) in-fiber optical sensor arrays. We show that the light outcoupled from the core of these BFBGs is radiated with sufficient optical power that it may be detected with a low-cost charge-coupled device (CCD) array. We present thorough system performance analysis that shows sufficient spectral-spatial resolution to decode sensors with a WDM separation of 75 ρm, signal-to-noise ratio greater than 45-dB bandwidth of 70 nm, and drift of only 0.1 ρm. We show the system to be polarization-state insensitive, making the BFBG-CCD spectral analysis technique a practical, extremely low-cost, alternative to traditional tunable filter approaches.

A fast response intrinsic humidity sensor based on an etched singlemode polymer fiber Bragg grating

A simple, low cost and fast response time intrinsic relative humidity sensor system based on an etched singlemode polymer fiber Bragg (POFBG) is presented in this paper. A macro-bend linear edge filter which converts the humidity induced wavelength shift into an intensity change is used as the interrogation technique. The singlemode POFBG is etched to micro-meters in diameter to improve the response time of the humidity sensor. A response time of 4.5 s is observed for a polymer FBG with a cladding diameter of 25 μm. The overall sensor system sensitivity was 0.23 mV/%RH. The etched POFBG humidity sensor shows anexponential decrease in response time with a decrease in fiber diameter. The developed sensor might have potential applications in a wide range of applications where fast and accurate real time humidity control is required. © 2013 Elsevier B.V. All rights reserved.

Graphene-assisted microfiber for optical-power-based temperature sensor

Combined the large evanescent field of microfiber with the high thermal conductivity of graphene, a sensitive all-fiber temperature sensor based on graphene-assisted micro fiber is proposed and experimentally demonstrated. Microfiber can be easily attached with graphene due to the electrostatic 6 force, resulting in an effective interaction between graphene and the evanescent field of microfiber. The change of the ambient temperature has a great influence on the conductivity of graphene, leading to the variation of the effective refractive index of microfiber. Consequently, the optical power transmission will be changed. The temperature sensitivity of 0.1018 dB/°C in the heating process and 0.1052 dB/°C in the cooling process as well as a high resolution of 0.0098 °C is obtained in the experiment. The scheme may have great potential in sensing fields owing to the advantages of high sensitivity, compact size, and low cost.

Optical loading sensor based on single polarization fiber laser incorporating an intra-cavity 45°-TFG

We have experimentally demonstrated an active loading sensor system based on a fiber ring laser with single-polarization output using an intra-cavity 45°-tilted fiber grating (45°-TFG). When the laser cavity fiber subjected to loading, the laser output is encoded with the load and can be measured and monitored by a power metre. A loading sensitivity as high as 0.033/ (kg·m-1) has been achieved using this laser. The experiment results clearly show that single polarization fiber laser may be developed to a low-cost high-sensitivity loading sensor system. © 2014 SPIE.

A self-referenced optical intensity sensor network using POFBGs for biomedical applications

This work bridges the gap between the remote interrogation of multiple optical sensors and the advantages of using inherently biocompatible low-cost polymer optical fiber (POF)-based photonic sensing. A novel hybrid sensor network combining both silica fiber Bragg gratings (FBG) and polymer FBGs (POFBG) is analyzed. The topology is compatible with WDM networks so multiple remote sensors can be addressed providing high scalability. A central monitoring unit with virtual data processing is implemented, which could be remotely located up to units of km away. The feasibility of the proposed solution for potential medical environments and biomedical applications is shown.

Fibre optic sensors for high speed hypervelocity impact studies and low velocity drop tests

The initial aim of this project was to develop a non-contact fibre optic based displacement sensor to operate in the harsh environment of a 'Light Gas Gun' (LGG), which can 'fire' small particles at velocities ranging from 1-8.4 km/s. The LGG is used extensively for research in aerospace to analyze the effects of high speed impacts on materials. Ideally the measurement should be made close to the centre of the impact to minimise corruption of the data from edge effects and survive the impact. A further requirement is that it should operate at a stand-off distance of ~ 8cm. For these reasons we chose to develop a pseudo con-focal intensity sensor, which demonstrated resolution comparable with conventional PVDF sensors combined with high survivability and low cost. A second sensor was developed based on 'Fibre Bragg Gratings' (FBG) which although requiring contact with the target the low weight and very small contact area had minimal effect on the dynamics of the target. The FBG was mounted either on the surface of the target or tangentially between a fixed location. The output signals from the FBG were interrogated in time by a new method. Measurements were made on composite and aluminium plates in the LGG and on low speed drop tests. The particle momentum for the drop tests was chosen to be similar to that of the particles used in the LGG.