Silicon-based Integrated Microarray Biochips for Biosensing and Biodetection Applications

The silicon-based integrated microarray biochip (IMB) is an inter-disciplinary research direction of microelectronics and biological science. It has caught the attention of both industry and academia, in applications such as deoxyribonucleic acid (DNA) and immunological detection, medical inspection and point-of-care (PoC) diagnosis, as well as food safety and environmental surveillance. Future biodetection strategies demand biochips with high sensitivity, miniaturization, integration, parallel, multi-target and even intelligence capabilities. In this chapter, a comprehensive investigation of current research on state-of-the-art silicon-based integrated microarray biochips is presented. These include the electrochemical biochip, magnetic tunnelling junction (MTJ) based biochip, giant magnetoresistance (GMR) biochip and integrated oscillator-based biochip. The principles, methodologies and challenges of the aforementioned biochips will also be discussed and compared from all aspects, e.g., sensitivity, fabrication complexity and cost, compatibility with silicon-based complementary metal-oxide-semiconductor (CMOS) technology, multi-target detection capabilities, signal processing and system integrations, etc. In this way, we discuss future silicon-based fully integrated biochips, which could be used for portable medical detection and low cost PoC diagnosis applications

Design and Implementation of an Integrated Biosensor Platform for Lab-on-a-Chip Diabetic Care Systems

Recent advances in semiconductor processing and microfabrication techniques allow the implementation of complex microstructures in a single platform or lab on chip. These devices require fewer samples, allow lightweight implementation, and offer high sensitivities. However, the use of these microstructures place stringent performance constraints on sensor readout architecture. In glucose sensing for diabetic patients, portable handheld devices are common, and have demonstrated significant performance improvement over the last decade. Fluctuations in glucose levels with patient physiological conditions are highly unpredictable and glucose monitors often require complex control algorithms along with dynamic physiological data. Recent research has focused on long term implantation of the sensor system. Glucose sensors combined with sensor readout, insulin bolus control algorithm, and insulin infusion devices can function as an artificial pancreas. However, challenges remain in integrated glucose sensing which include degradation of electrode sensitivity at the microscale, integration of the electrodes with low power low noise readout electronics, and correlation of fluctuations in glucose levels with other physiological data. This work develops 1) a low power and compact glucose monitoring system and 2) a low power single chip solution for real time physiological feedback in an artificial pancreas system. First, glucose sensor sensitivity and robustness is improved using robust vertically aligned carbon nanofiber (VACNF) microelectrodes. Electrode architectures have been optimized, modeled and verified with physiologically relevant glucose levels. Second, novel potentiostat topologies based on a difference-differential common gate input pair transimpedance amplifier and low-power voltage controlled oscillators have been proposed, mathematically modeled and implemented in a 0.18μm [micrometer] complementary metal oxide semiconductor (CMOS) process. Potentiostat circuits are widely used as the readout electronics in enzymatic electrochemical sensors. The integrated potentiostat with VACNF microelectrodes achieves competitive performance at low power and requires reduced chip space. Third, a low power instrumentation solution consisting of a programmable charge amplifier, an analog feature extractor and a control algorithm has been proposed and implemented to enable continuous physiological data extraction of bowel sounds using a single chip. Abdominal sounds can aid correlation of meal events to glucose levels. The developed integrated sensing systems represent a significant advancement in artificial pancreas systems

Noise Characterization, Modeling, and Reduction for In Vivo Neural Recording

Studying signal and noise properties of recorded neural data is critical in developing more efficient algorithms to recover the encoded information. Important issues exist in this research including the variant spectrum spans of neural spikes that make it difficult to choose a globally optimal bandpass filter. Also, multiple sources produce aggregated noise that deviates from the conventional white Gaussian noise. In this work, the spectrum variability of spikes is addressed, based on which the concept of adaptive bandpass filter that fits the spectrum of individual spikes is proposed. Multiple noise sources have been studied through analytical models as well as empirical measurements. The dominant noise source is identified as neuron noise followed by interface noise of the electrode. This suggests that major efforts to reduce noise from electronics are not well spent. The measured noise from in vivo experiments shows a family of 1/f^x spectrum that can be reduced using noise shaping techniques. In summary, the methods of adaptive bandpass filtering and noise shaping together result in several dB signal-to-noise ratio (SNR) enhancement

A high performance ASIC for electrical and neurochemical traumatic brain injury monitoring

Traumatic Brain Injury (TBI) can be defined as a non-degenerative, non-congenital brain trauma due to an external mechanical force. TBI is a major cause of death and disability in all age groups and the leading cause of death and disability in working people and among young adults. This Thesis presents the first application specific integrated chip (ASIC) for monitoring patients suffering from TBI. The microelectronic chip was designed to meet the demands of processing physiological signals for an alternative method of TBI monitoring. It has been studied that by monitoring electrical (ECoG) and chemical (glucose, lactate and potassium) signals, the report of spreading depolarisation (SD) waves could be a good indicator for an upcoming secondary brain injury. The ultimate aim of this Thesis has been to support the idea of a “behind-the-ear” micro-platform, which could enable the monitoring of mobile (or mobilized) patients suffering a TBI who, currently, are not monitored. Switched-capacitor (SC) circuits have been adopted for the implementation of both current and voltage analogue front-ends (AFEs). Advanced techniques to minimise noise and improve the noise performance of the circuit were employed. Moreover, a digitally enabled automatic transimpedance gain control circuit, suitable for current analogue front-ends, was developed and tested in order to provide an automated way to adjust the gain and to counterbalance for the drop in sensitivity of the biosensors due to drift. Measured results confirming the operation of the TBI ASIC and its sub-circuits are reported. Finally, a novel circuit that mimics the Butler-Volmer dynamics is presented. The basic building blocks arise from the combination of Translinear (TL) Circuits and the Non- linear Bernoulli Cell Formalism (NBCF). The developed electrical equivalent circuit has been compared to an ideal model, which was developed in MATLAB. The robustness of the microelectronic system was evaluated by means of Monte Carlo simulations.Open Acces

An implantable micro-system for neural prosthesis control and sensory feedback restoration in amputees

In this work, the prototype of an electronic bi-directional interface between the Peripheral Nervous System (PNS) and a neuro-controlled hand prosthesis is presented. The system is composed of two Integrated Circuits (ICs): a standard CMOS device for neural recording and a High Voltage (HV) CMOS device for neural stimulation. The integrated circuits have been realized in two different 0.35μm CMOS processes available fromAustriaMicroSystem(AMS). The recoding IC incorporates 8 channels each including the analog front-end and the A/D conversion based on a sigma delta architecture. It has a total area of 16.8mm2 and exhibits an overall power consumption of 27.2mW. The neural stimulation IC is able to provide biphasic current pulses to stimulate 8 electrodes independently. A voltage booster generates a 17V voltage supply in order to guarantee the programmed stimulation current even in case of high impedances at the electrode-tissue interface in the order of tens of k­. The stimulation patterns, generated by a 5-bit current DAC, are programmable in terms of amplitude, frequency and pulse width. Due to the huge capacitors of the implemented voltage boosters, the stimulation IC has a wider area of 18.6mm2. In addition, a maximum power consumption of 29mW was measured. Successful in-vivo experiments with rats having a TIME electrode implanted in the sciatic nerve were carried out, showing the capability of recording neural signals in the tens of microvolts, with a global noise of 7μVrms , and to selectively elicit the tibial and plantarmuscles using different active sites of the electrode. In order to get a completely implantable interface, a biocompatible and biostable package was designed. It hosts the developed ICs with the minimal electronics required for their proper operation. The package consists of an alumina tube closed at both extremities by two ceramic caps hermetically sealed on it. Moreover, the two caps serve as substrate for the hermetic feedthroughs to enable the device powering and data exchange with the external digital controller implemented on a Field-Programmable Gate Array (FPGA) board. The package has an outer diameter of 7mm and a total length of 26mm. In addition, a humidity and temperature sensor was also included inside the package to allow future hermeticity and life-time estimation tests. Moreover, a wireless, wearable and non-invasive EEG recording system is proposed in order to improve the control over the artificial limb,by integrating the neural signals recorded from the PNS with those directly acquired from the brain. To first investigate the system requirements, a Component-Off-The-Shelf (COTS) device was designed. It includes a low-power 8- channel acquisition module and a Bluetooth (BT) transceiver to transmit the acquired data to a remote platform. It was designed with the aimof creating a cheap and user-friendly system that can be easily interfaced with the nowadays widely spread smartphones or tablets by means of a mobile-based application. The presented system, validated through in-vivo experiments, allows EEG signals recording at different sample rates and with a maximum bandwidth of 524Hz. It was realized on a 19cm2 custom PCB with a maximum power consumption of 270mW

New Directions in Impedance Spectroscopy for High Accuracy, Augmented Information Extraction and Low Power Implementation

This thesis provides new directions in the impedance spectroscopy, making it an interesting investigation technique for emerging smart sensors. Modern technologies increasingly require sensors capable of giving accurate measurements extracted among a lot of undesired surrounding information while maintaining low power consumptions. In this scenario, the main focuses of this thesis are: 1) developing an accurate complex impedance system, 2) extracting the augmented information using multivariate statistical analysis and 3) implementing IS-based systems with low power consumptions. The first project shows the design of a miniaturized, low power and accurate vector analyser for multi-parameter measurements in real-time. It is a versatile platform well-suited to be interfaced with various impedance-based sensors. The vector analyser, based on an accurate application specific integrated circuit and a digital interface, has been statistically characterized in order to evaluate accuracy and resolution. The validation of the entire system was performing on two real-time biomedical applications. The second project concerns the combination of powerful statistical methods inside moisture content sensors. The multivariate statistical approaches boost the prediction capability of the sensors exploiting the impedance mismatch between a transmitting and reflecting excitation on a soil. Two probe systems have been manufactured and associated with linear and non-linear models for being tested on three soil types. The third project shows a low-power implementation of an impedance sensor based on a digital random excitation. The entire system is almost digital, made up by an ultra-low power platform with the aim to become a wearable device. In future developments, these new investigated directions can be simultaneously applied in the design of IS based sensors which extract the desired information with high accuracy and reduced power budget. The potential of such improved system can be employed in a lot of smart sensors, involving electrochemical, environmental, food, biological applications and wearable devices

Design, fabrication, characterization and reliability study of CMOS-MEMS Lorentz-Force magnetometers

Tesi en modalitat de compendi de publicacionsToday, the most common form of mass-production semiconductor device fabrication is Complementary Metal-Oxide Semiconductor (CMOS) technology. The dedicated Integrated Circuit (IC) interfaces of commercial sensors are manufactured using this technology. The sensing elements are generally implemented using Micro-Electro-Mechanical-Systems (MEMS), which need to be manufactured using specialized micro-machining processes. Finally, the CMOS circuitry and the MEMS should ideally be combined in a single package. For some applications, integration of CMOS electronics and MEMS devices on a single chip (CMOS-MEMS) has the potential of reducing fabrication costs, size, parasitics and power consumption, compared to other integration approaches. Remarkably, a CMOS-MEMS device may be built with the back-end-of-line (BEOL) layers of the CMOS process. But, despite its advantages, this particular approach has proven to be very challenging given the current lack of commercial products in the market. The main objective of this Thesis is to prove that a high-performance MEMS, sealed and packaged in a standard package, may be accurately modeled and manufactured using the BEOL layers of a CMOS process in a reliable way. To attain this, the first highly reliable novel CMOS-MEMS Lorentz Force Magnetometer (LFM) was successfully designed, modeled, manufactured, characterized and subjected to several reliability tests, obtaining a comparable or superior performance to the typical solid-state magnetometers used in current smartphones. A novel technique to avoid magnetic offsets, the main drawback of LFMs, was presented and its performance confirmed experimentally. Initially, the issues encountered in the manufacturing process of MEMS using the BEOL layers of the CMOS process were discouraging. Vapor HF release of MEMS structures using the BEOL of CMOS wafers resulted in undesirable damaging effects that may lead to the conclusion that this manufacturing approach is not feasible. However, design techniques and workarounds for dealing with the observed issues were devised, tested and implemented in the design of the LFM presented in this Thesis, showing a clear path to successfully fabricate different MEMS devices using the BEOL.Hoy en día, la forma más común de producción en masa es una tecnología llamada Complementary Metal-Oxide Semiconductor (CMOS). La interfaz de los circuitos integrados (IC) de sensores comerciales se fabrica usando, precisamente, esta tecnología. Actualmente es común que los sensores se implementen usando Sistemas Micro-Electro-Mecánicos (MEMS), que necesitan ser fabricados usando procesos especiales de micro-mecanizado. En un último paso, la circuitería CMOS y el MEMS se combinan en un único elemento, llamado package. En algunas aplicaciones, la integración de la electrónica CMOS y los dispositivos MEMS en un único chip (CMOS-MEMS) alberga el potencial de reducir los costes de fabricación, el tamaño, los parásitos y el consumo, al compararla con otras formas de integración. Resulta notable que un dispositivo CMOS-MEMS pueda ser construido con las capas del back-end-of-line (BEOL) de un proceso CMOS. Pero, a pesar de sus ventajas, este enfoque ha demostrado ser un gran desafío como demuestra la falta de productos comerciales en el mercado. El objetivo principal de esta Tesis es probar que un MEMS de altas prestaciones, sellado y empaquetado en un encapsulado estándar, puede ser correctamente modelado y fabricado de una manera fiable usando las capas del BEOL de un proceso CMOS. Para probar esto mismo, el primer magnetómetro CMOS-MEMS de fuerza de Lorentz (LFM) fue exitosamente diseñado, modelado, fabricado, caracterizado y sometido a varias pruebas de fiabilidad, obteniendo un rendimiento comparable o superior al de los típicos magnetómetros de estado sólido, los cuales son usados en móviles actuales. Cabe destacar que en esta Tesis se presenta una novedosa técnica con la que se evitan offsets magnéticos, el mayor inconveniente de los magnetómetros de fuerza Lorentz. Su efectividad fue confirmada experimentalmente. En los inicios, los problemas asociados al proceso de fabricación de MEMS usando las capas BEOL de obleas CMOS resultaba desalentador. Liberar estructuras MEMS hechas con obleas CMOS con vapor de HF producía efectos no deseados que bien podrían llevar a la conclusión de que este enfoque de fabricación no es viable. Sin embargo, se idearon y probaron técnicas de diseño especiales y soluciones ad-hoc para contrarrestar estos efectos no deseados. Se implementaron en el diseño del magnetómetro de Lorentz presentado en esta Tesis, arrojando excelentes resultados, lo cual despeja el camino hacia la fabricación de diferentes dispositivos MEMS usando las capas BEOL.Postprint (published version

Smart Devices and Systems for Wearable Applications

Wearable technologies need a smooth and unobtrusive integration of electronics and smart materials into textiles. The integration of sensors, actuators and computing technologies able to sense, react and adapt to external stimuli, is the expression of a new generation of wearable devices. The vision of wearable computing describes a system made by embedded, low power and wireless electronics coupled with smart and reliable sensors - as an integrated part of textile structure or directly in contact with the human body. Therefore, such system must maintain its sensing capabilities under the demand of normal clothing or textile substrate, which can impose severe mechanical deformation to the underlying garment/substrate. The objective of this thesis is to introduce a novel technological contribution for the next generation of wearable devices adopting a multidisciplinary approach in which knowledge of circuit design with Ultra-Wide Band and Bluetooth Low Energy technology, realization of smart piezoresistive / piezocapacitive and electro-active material, electro-mechanical characterization, design of read-out circuits and system integration find a fundamental and necessary synergy. The context and the results presented in this thesis follow an “applications driven” method in terms of wearable technology. A proof of concept has been designed and developed for each addressed issue. The solutions proposed are aimed to demonstrate the integration of a touch/pressure sensor into a fabric for space debris detection (CApture DEorbiting Target project), the effectiveness of the Ultra-Wide Band technology as an ultra-low power data transmission option compared with well known Bluetooth (IR-UWB data transmission project) and to solve issues concerning human proximity estimation (IR-UWB Face-to-Face Interaction and Proximity Sensor), wearable actuator for medical applications (EAPtics project) and aerospace physiology countermeasure (Gravity Loading Countermeasure Skinsuit project)

Engineering design instrumentation for life detection planetary exploration missions

The aim of the research documented in this thesis was to explore issues associated with the development of instrumentation for life detection and characterisation in a planetary exploration context. Within this aim, the following objectives had to be achieved: 1. To consider current and near-future single molecule detection (ultra-low lower limit of detection) analytical techniques that would be compatible with development into a Space qualifiable in situ analytical instrument for the detection of biomarkers in a planetary exploration context. 2. To practically consider the consequences of Planetary Protection and Contamination Control on the development of a sample return instrumentation in a planetary exploration context. 3. To consider the implications of flying an in situ instrument on-board a stratospheric balloon platform in order to apply them into a specific planetary exploration mission: In order to achieve the objectives described above, the following work was pursued: A desk-based European Space Agency (ESA) study was carried out which entailed producing a literature review on single molecule detection technologies that had to be validated by the expert community. This was done by organising an International Workshop on Single Molecule Detection Technologies for Space Applications in March 2009 at Cranfield University, UK. The approved technologies then had to be analysed with standard analytical techniques (i.e., tradeoffs) in order to propose a specific technology for development and present its breadboard implementation and test plans at the end of the study. A sample return experiment implementing PP&CC constraints and protocols was designed, built, tested and flown on-board the ESA, Swedish Space Corporation (SSC), Swedish National Space Board (SNSB) and German Space Agency (DLR) BEXUS stratospheric balloon platform. The biological and engineering results obtained from the sample return flight were then analysed and lessons learnt obtained for future flights. Another desk-based study was performed to research future stratospheric balloon platforms for the exploration of Venus’ cloud layer. The in situ instrument previously proposed for the detection of biomarkers for planetary exploration missions was then put forward as a possible payload for a Venusian stratospheric balloon platform and approved by experts during the Venus Exploration Analysis Group (VEXAG) conference held in August 2011 in Washington D.C, USA. The first part of the research involved studying ultra-low lower limit of detection technologies as these have the potential to impact significantly on the technological and scientific requirements of future Space missions. Two systems were proposed: one based on Tandem Mass Spectrometry (with Cylindrical Ion Trap analysers) followed by Surface Enhanced Raman Scattering spectroscopy to create an MS/MS-SERS instrument for the detection of astrobiology biomarkers in Martian regolith, Europan ice and samples from Titan’s hydrocarbon lakes; and a second one as a Stand-Alone SERS system for the detection of biomarkers in Enceladean plumes, Venusian clouds and cometary coma. The second part of the research practically explored the design of instrumentation for stratospheric balloon platforms. CASS•E, the Cranfield Astrobiological Stratospheric Sampling Experiment, was a life detection experiment that aimed to be capable of detecting stratospheric microorganisms. The experiment consisted of a pump which drew air from the Stratosphere through a 0.2 μm collection filter which retained any microorganisms and >0.2 μm particulates present in the pumped air. Due to the expected rarity of microbes in the Stratosphere compared to the known levels of contamination at ground level, Planetary Protection and Contamination Control (PP&CC)constraints were introduced. Therefore PP&CC protocols were followed to implement Space qualified cleaning and sterilisation techniques; biobarrier technology was implemented to prevent re-contamination of the instrument after sterilisation; and cleanliness and contamination was monitored throughout assembly, integration and testing. The third part of the research demonstrated how an instrument from the first part of the study could be proposed as a payload on-board a stratospheric balloon platform with a focused mission context, i.e., a life detection mission for Venus. Therefore, the research concluded with the proposal of a payload for a Venus mission based on SERS technology on-board a stratospheric balloon platform to search for life above or in the mid Venusian cloud cover.EThOS - Electronic Theses Online ServiceGBUnited Kingdo