Biological neural networks: an application to odor information processing

Treballs Finals de Grau de Física, Facultat de Física, Universitat de Barcelona, Any: 2014, Tutor: Agustí GutiérrezTraditionally, there has been a lot of research on how the brain manages visual and auditory inputs, but not that much attention has been devoted to the olfactory sensory system due, in part, to the complex nature of volatile organic compounds (VOCs). The aim of this project is to understand and build a computational neural model of the first stage of the olfactory pathway: the glomerular layer. Some experts in the field, supported by experimental evidence, point at this first stage as the neural location where an important aspect of odor information processing takes place: odor segregation. Our working hypothesis states that this input layer performs normalization and contrast and concentration enhancement over odorants before the odorant information is conveyed to deeper olfactory structures for detection. By performing an experiment on the computed neural network, we will be able to determine whether and how this odor segregation occurs. This is achieved by statistical analysis of the structure of the high-dimensional output space, understood as the spiking frequency and synchronization of glomerular neurons firing patterns

Large area in situ fabrication of Poly(pyrrole)-nanowires on flexible thermoplastic films using Nanocontact printing

Abstract: Highly efficient nano-engineering tools will certainly revolutionize the biomedical and sensing devices research and development in the years to come. Here, we present a novel high performance conducting poly(pyrrole) nanowires (PPy-NW) patterning technology on thermoplastic surfaces (poly(ethylene terephthalate (PETE), poly(ethylene 2,6-naphthalate (PEN), polyimide (PI), and cyclic olefin copolymer (COC)) using nanocontact printing and controlled chemical polymerization (nCP-CCP) technique. The technique uses a commercial compact disk (CD) as a template to produce nanopatterned polydimethylsiloxane (PDMS) stamps. The PDMS nanopatterned stamp was applied to print the PPy-NWs and the developed technology of nCP-CCP produced 3D conducting nanostructures. This new and very promising nanopatterning technology was achieved in a single step and with a low cost of fabrication over large areas

Transparent nanostructured metal oxides for chemical biosensors: towards point-of-care environments

[eng] There is an increasing need for developing innovative, versatile and low-cost point-of-care (POC) systems capable of screening for at early stages of development. POC systems usually consist of a biosensor part integrated in an electronic circuit and eventually a microfluidic system to manage the body fluid samples. The aim of this doctoral thesis is to investigate several ways of improving POC technology. On the one hand, biosensors currently integrated into POC systems have limitations. A wide variety of important analytes cannot be properly detected and quantified, and methods supported by a powerful electronic systems that supply the necessary energy to trigger a measurable event that can be monitored are required. For this, adequate sensing substrates are required that allow the coupling of analytes and other biomolecules and enable the detection of chemical reactions occurring at their surfaces. Besides, the complex electronic circuitry capable of simultaneously exciting the sensor and monitoring its response must be redesigned into a low-cost and miniaturized format to be integrated into POC systems. Electrochemical and optical biosensors have become relevant in point-of-care technology due to the versatility of POC systems based on such transducing principles, which provide the sensors with high sensitivities and specificities. In particular, sensitivity may become badly affected by the miniaturization of sensors and devices. Thus, the need for reducing the surface of sensing electrodes and yet maintaining the sensitivity has boosted the research and development of nanostructured surfaces. The high surface-to- volume ratio (SVR) presented by nanostructures makes them extremely interesting for the detection of biomolecules, since an increase of surface enables the interaction with a big amount of small-sized molecules and this implies an increase of sensitivity and the possibility to reduce the sensor size. In this thesis, nanostructured indium tin oxide (ITO) is proposed as working electrode (WE) for electrochemical biosensors. The first part of this thesis consists in a study of ITO properties and its electrical, optical, electrochemical and structural characterization both as a thin film and as nanostructured electrodes prepared by electron beam evaporation onto silicon and glass substrates. Moreover, the interaction of nanostructured ITO with some molecules known as crosslinkers, which allow subsequent functionalization of surfaces with biomolecules, has also been studied in the frame of this thesis. Finally, several immunoassays were performed using nanostructured ITO as substrate, with special attention to the detection of several concentrations of tumour necrosis factor α (TNF-α). On the other hand, several electrochemical sensor mechanisms were studied. These were based upon different ways of electrically attacking the sensor and processing its response, and included potentiometry, amperometry and electrochemical impedance spectroscopy. A low-cost and miniaturized device implementing electrochemical impedance spectroscopy measurements was designed and developed for the detection of several concentrations of TNF–α biomarker with an array of eight parallel gold-based microelectrodes. Besides, we also designed the electronics for performing two-electrode amperometry and potentiometry. The latter was tested on nanostructured ITO electrodes covered with a doped conducting polymer, which was sensitive to pH changes in aqueous media. To synthesize, this thesis gathers several proposals for improving current POC systems, regarding both the biosensor and the electronic parts, employing an important biomarker in the biomedical area for the measurements and proofs of concept, and being such approaches extensible to the environmental field.[spa] Existe una creciente necesidad de desarrollar sistemas de punto de cuidado (POC) innovadores, versátiles y de bajo coste, capaces de detectar enfermedades en estadios de desarrollo tempranos. Un sistema POC consiste en un biosensor integrado en un sistema electrónico y eventualmente un sistema microfluídico que gestione las muestras de fluidos biológicos. El objetivo general de esta tesis es investigar distintas posibilidades de mejorar la tecnología POC. Los sistemas biosensores actualmente integrados en sistemas POC son limitados, y requieren de métodos que se apoyen en un potente sistema electrónico. Para esto, se requiere por un lado de sustratos adecuados que permitan tanto el acoplo de biomoléculas como la detección de reacciones químicas ocurridas en su superficie; por otro lado, es necesaria una potente circuitería electrónica que pueda ser miniaturizada y de bajo consumo. Los biosensores electroquímicos y ópticos han tomado mucha relevancia en sistemas POC debido a su alta sensibilidad y especificidad, aunque éstas pueden verse gravemente afectadas por la miniaturización de los dispositivos. Por ello, la elevada relación superficie-volumen que presentan las nanoestructuras las hace especialmente interesantes para biodetección. En esta tesis, se propone el óxido de indio dopado con estaño (ITO) nanoestructurado como material de electrodo de trabajo en biosensores electroquímicos. En la primera parte de esta tesis se han estudiado las propiedades del ITO, y se ha caracterizado eléctrica, óptica, electroquímica y estructuralmente, a partir de muestras preparadas sobre silicio y sobre vidrio mediante evaporación por haz de electrones. Se ha estudiado su interacción con moléculas crosslinkers, y se han realizado varios inmunoensayos usando el ITO nanoestructurado como sustrato. Se han estudiado distintos mecanismos de medida de sensores electroquímicos; por espectroscopía de impedancias se han detectado distintas concentraciones del biomarcador TNF-α. Se ha diseñado la electrónica necesaria para realizar medidas de amperometría con dos electrodos, así como de potenciometría, ensayando este último sistema con ITO nanoestructurado y modificado sensible a cambios de pH. En síntesis, esta tesis recoge algunas propuestas para la mejora de los sistemas POC actuales, tanto en la cuestión biosensora como en la parte electrónica, usando para las medidas y pruebas de concepto un biomarcador importante en el ámbito biomédico

Towards nanostructured ITO-based electrochemical sensors: Fabrication, characterization and functionalization

The need for miniaturized, low-cost and ultrasensitive electrochemical sensors has motivated the search and study of new nanostructured materials. We propose nanostructured indium tin oxide (ITO) electrodes as a promising platform due to their good electrical conductivity, transparency to visible wavelengths and high surface-to-volume ratio. The nanostructured electrodes were fabricated by electron beam evaporation, and electrochemical techniques were used to quantify more than a 40% increase in electrochemical surface area compared to thin ITO films. The electrodes were derivatized with organosilanes and coated with a molecule providing redox activity. Indeed, an increase in detectability of more than 400% was observed with respect to thin films, indicating the potential viability of nanostructured ITO-based electrochemical biosensors

Low-cost impedance measurements for lab-on-a-chip architectures: Towards potentiostat miniaturization

The development of miniaturized potentiostats capable of measuring in a wide range of conditions and with full characteristics (e.g., wide bandwidth and capacitive/inductive contribution to sensor's impedance) is still an unresolved challenge in bioelectronics. We present a simple analogue design coupled to a digital filter based on a lock-in amplifier as an alternative to complex architectures reported hitherto. A low-cost, miniaturized and fully integrated acquisition electronic system was developed, tested for a fully integrated three-lead electrochemical biosensor and benchmarked against a commercial potentiostat. The portable potentiostat was coupled to an array of miniaturized gold working electrodes to perform complex impedance analyses for tumor necrosis factor α (TNF-α) cytokine detection. This wearable potentiostat is very promising for the development of low-cost point-of-care (POC) with low power consumption

Devices and methods for multiplexing liquid in biosensor micro-chambers

A biosensors device for simultaneous multiple-analyte analysis by a plurality of biosensors dipped in single biosensor micro-chamber flooded with a functional liquid flowing to the biosensor micro-chambers from a fluidic circuit with no symmetry prerequisite comprises micro-valves operably associated to biosensor micro-chambers for selectively allowing the crossing of a functional liquid to the biosensor micro-chambers, a biosensor micro-chamber at a time, according to a pulsating flow mode so that the total flow rate can be greatly reduced and a predetermined amount of a pressured functional liquid is multiplexed to biosensor micro-chambers. Companion methods are defined for such a biosensors device.Dispositivo de biosensores para análisis simultáneo de múltiples analitos por una pluralidad de biosensores sumergidos en una microcámara biosensora inundada con un líquido funcional que fluye a las microcámaras biosensoras a partir de un circuito fluídico sin ningún prerequisito de simetría que comprende microválvulas asociadas operativamente a las microcámaras biosensoras para permitir selectivamente el cruce de un líquido funcional a las microcámaras biosensoras, una microcámara biosensora cada vez, de acuerdo con un modo de flujo pulsante, de manera que el caudal total puede ser reducido en gran medida y una cantidad predeterminada de un líquido funcional presurizado es multiplexado hacia las microcámaras biosensoras. Se definen métodos asociados para dicho dispositivo de biosensores

Evaluation of MOX sensor characteristics in ultra-low power operation modes: Application to a semi-passive RFID tag for food logistics

Most of the battery powered systems with integrated sensors need low power consumption modes to enlarge the operation time. In the case of the fruit logistic chain, the fruit quality may be controlled by the detection of some gases as ethylene, acetaldehyde and ammonia, that are related to maturation, oxygen stress and refrigeration leakage. We report the integration of an ultra-low power (ULP) metal oxide (MOX) sensor array inside a Radio Frequency IDentification (RFID) 13.56 MHz ISO/IEC 15693 compliant tag with temperature, humidity and light sensors and data logging capabilities. Pulsed Temperature Operation (PTO), which consists in switching on and off the sensor heater, was used to reduce power consumption more than three orders of magnitude, from 14 mW down to 7 μW. The sensor behavior was characterized in terms sensitivity for ammonia

Large area in situ fabrication of Poly(pyrrole)-nanowires on flexible thermoplastic films using Nanocontact printing

Abstract: Highly efficient nano-engineering tools will certainly revolutionize the biomedical and sensing devices research and development in the years to come. Here, we present a novel high performance conducting poly(pyrrole) nanowires (PPy-NW) patterning technology on thermoplastic surfaces (poly(ethylene terephthalate (PETE), poly(ethylene 2,6-naphthalate (PEN), polyimide (PI), and cyclic olefin copolymer (COC)) using nanocontact printing and controlled chemical polymerization (nCP-CCP) technique. The technique uses a commercial compact disk (CD) as a template to produce nanopatterned polydimethylsiloxane (PDMS) stamps. The PDMS nanopatterned stamp was applied to print the PPy-NWs and the developed technology of nCP-CCP produced 3D conducting nanostructures. This new and very promising nanopatterning technology was achieved in a single step and with a low cost of fabrication over large areas