Flexible microimplants for in vivo sensing

The work in this thesis develops two types of microimplants for the application of cardiovascular in vivo biomedical sensing, one for short-term diagnosis and the other for long-term monitoring.

Despite advances in diagnosis and therapy, atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality in the Western world. Predicting metabolically active atherosclerotic plaques has remained an unmet clinical need. A stretchable impedance sensor manifested as a pair of quasi-concentric microelectrodes was developed to detect unstable intravascular. By integrating the impedance sensor with a cardiac catheter, high-resolution Electrochemical Impedance Spectroscopy (EIS) measurements can be conducted during cardiac catheterization. An inflatable silicone balloon is added to the sensor to secure a well-controlled contact with the plaque under test in vivo. By deploying the device to the explants of NZW rabbit aorta and live animals, distinct EIS measurements were observed for unstable atherosclerotic plaques that harbored active lipids and inflammatory cells.

On the other hand, zebrafish (Danio rerio) is an emerging genetic model for heart regenerative medicine. In humans, myocardial infarction results in the irreversible loss of cardiomyocytes. Zebrafish hearts can fully regenerate after two months with 20% ventricular resection. Long-term electrocardiogram (ECG) recording can characterize the heart regeneration in a functional dimension. A flexible microelectrode membrane was developed to be percutaneously implanted onto a zebrafish heart and record epicardial ECG signals from specific regions on it. Region-specific aberrant cardiac signals were obtained from injured and regenerated hearts. Following that, in order to achieve continuous and wireless recording from non-sedated and non-restricted small animal models, a wireless ECG recording system was designed for the microelectrode membrane, prototyped on a printed circuit board and demonstrated on a one-day-old neonatal mouse. Furthermore, a flexible and compact parylene C printed circuit membrane was used as the integration platform for the wireless ECG recording electronics. A substantially miniature wireless ECG recording system was achieved.

Acceleration Sensing, Feedback Cooling, and Nonlinear Dynamics with Nanoscale Cavity-Optomechanical Devices

Light has long been used for the precise measurement of moving bodies, but the burgeoning field of optomechanics is concerned with the interaction of light and matter in a regime where the typically weak radiation pressure force of light is able to push back on the moving object. This field began with the realization in the late 1960's that the momentum imparted by a recoiling photon on a mirror would place fundamental limits on the smallest measurable displacement of that mirror. This coupling between the frequency of light and the motion of a mechanical object does much more than simply add noise, however. It has been used to cool objects to their quantum ground state, demonstrate electromagnetically-induced-transparency, and modify the damping and spring constant of the resonator. Amazingly, these radiation pressure effects have now been demonstrated in systems ranging 18 orders of magnitude in mass (kg to fg).

In this work we will focus on three diverse experiments in three different optomechanical devices which span the fields of inertial sensors, closed-loop feedback, and nonlinear dynamics. The mechanical elements presented cover 6 orders of magnitude in mass (ng to fg), but they all employ nano-scale photonic crystals to trap light and resonantly enhance the light-matter interaction. In the first experiment we take advantage of the sub-femtometer displacement resolution of our photonic crystals to demonstrate a sensitive chip-scale optical accelerometer with a kHz-frequency mechanical resonator. This sensor has a noise density of approximately 10 micro-g/rt-Hz over a useable bandwidth of approximately 20 kHz and we demonstrate at least 50 dB of linear dynamic sensor range. We also discuss methods to further improve performance of this device by a factor of 10.

In the second experiment, we used a closed-loop measurement and feedback system to damp and cool a room-temperature MHz-frequency mechanical oscillator from a phonon occupation of 6.5 million down to just 66. At the time of the experiment, this represented a world-record result for the laser cooling of a macroscopic mechanical element without the aid of cryogenic pre-cooling. Furthermore, this closed-loop damping yields a high-resolution force sensor with a practical bandwidth of 200 kHZ and the method has applications to other optomechanical sensors.

The final experiment contains results from a GHz-frequency mechanical resonator in a regime where the nonlinearity of the radiation-pressure interaction dominates the system dynamics. In this device we show self-oscillations of the mechanical element that are driven by multi-photon-phonon scattering. Control of the system allows us to initialize the mechanical oscillator into a stable high-amplitude attractor which would otherwise be inaccessible. To provide context, we begin this work by first presenting an intuitive overview of optomechanical systems and then providing an extended discussion of the principles underlying the design and fabrication of our optomechanical devices.

Sensing and Actuation from Biology to Electronics

We introduce an in vitro diagnostic magnetic biosensing platform for immunoassay and nucleic acid detection. The platform has key characteristics for a point-of-use (POU) diagnostic: portability, low-power consumption, low cost, and multiplexing capability. As a demonstration of capabilities, we use this platform for the room temperature, amplification-free detection of a 31 bp DNA oligomer and interferon-gamma (a protein relevant for tuberculosis diagnosis). Reliable assay measurements down to 100 pM for the DNA and 1 pM for the protein are demonstrated. We introduce a novel "magnetic freezing" technique for baseline measurement elimination and to enable spatial multiplexing. We have created a general protocol for adapting integrated circuit (IC) sensors to any of hundreds of commercially available immunoassay kits and custom designed DNA sequences.

We also introduce a method for immunotherapy treatment of malignant gliomas. We utilize leukocytes internalized with immunostimulatory nanoparticle-oligonucleotide conjugates to localize and retain immune cells near the tumor site. As a proof-of-principle, we develop a novel cell imaging and incubation chamber for in vitro magnetic motility experiments. We use the apparatus to demonstrate the controlled movement of magnetically loaded THP-1 leukocytes.

Finally, we introduce an IC transmitter and power ampli er (PA) that utilizes electronic digital infrastructure, sensors, and actuators to self-heal and adapt to process, dynamic, and environmental variation. Traditional IC design has achieved incredible degrees of reliability by ensuring that billions of transistors on a single IC die are all simultaneously functional. Reliability becomes increasingly difficult as the size of a transistor shrinks. Self-healing can mitigate these variations.

Cavity-enhanced spectroscopies for applications of remote sensing, chemical kinetics and detection of radical species

This thesis describes applications of cavity enhanced spectroscopy towards applications of remote sensing, chemical kinetics and detection of transient radical molecular species. Both direct absorption spectroscopy and cavity ring-down spectroscopy are used in this work. Frequency-stabilized cavity ring-down spectroscopy (FS-CRDS) was utilized for measurements of spectral lineshapes of O₂ and CO₂ for obtaining laboratory reference data in support of NASA’s OCO-2 mission. FS-CRDS is highly sensitive (> 10 km absorption path length) and precise (> 10000:1 SNR), making it ideal to study subtle non-Voigt lineshape effects. In addition, these advantages of FS-CRDS were further extended for measuring kinetic isotope effects: A dual-wavelength variation of FS-CRDS was used for measuring precise D/H and ¹³C/¹²C methane isotope ratios (sigma>0.026%) for the purpose of measuring the temperature dependent kinetic isotope effects of methane oxidation with O(¹D) and OH radicals. Finally, direct absorption spectroscopic detection of the trans-DOCO radical via a frequency combs spectrometer was conducted in collaboration with professor Jun Ye at JILA/University of Colorado.

I. Baryon-antibaryon phase transition at high temperature. II. Inclusive virtual photon-hadron reactions in the parton model

Part I

Present experimental data on nucleon-antinucleon scattering allow a study of the possibility of a phase transition in a nucleon-antinucleon gas at high temperature. Estimates can be made of the general behavior of the elastic phase shifts without resorting to theoretical derivation. A phase transition which separates nucleons from antinucleons is found at about 280 MeV in the approximation of the second virial coefficient to the free energy of the gas.

Part II

The parton model is used to derive scaling laws for the hadrons observed in deep inelastic electron-nucleon scattering which lie in the fragmentation region of the virtual photon. Scaling relations are obtained in the Bjorken and Regge regions. It is proposed that the distribution functions become independent of both q² and ν where the Bjorken and Regge regions overlap. The quark density functions are discussed in the limit x→1 for the nucleon octet and the pseudoscalar mesons. Under certain plausible assumptions it is found that only one or two quarks of the six types of quarks and antiquarks have an appreciable density function in the limit x→1. This has implications for the quark fragmentation functions near the large momentum boundary of their fragmentation region. These results are used to propose a method of measuring the proton and neutron quark density functions for all x by making measurements on inclusively produced hadrons in electroproduction only. Implications are also discussed for the hadrons produced in electron-positron annihilation.

Leitura virtual em língua espanhola: a intervenção dos elementos linguísticos presentes em blogs de professores

Esta dissertação tem como objetivo analisar a intervenção de elementos linguísticos no processo leitor em espanhol como língua estrangeira (E/LE) ,em ambiente virtual, de docente desse idioma. A partir desse objetivo macro, estabelecemos um recorte e nos focamos na análise de como/se elementos linguísticos mais característicos de uma linguagem coloquial podem afetar mais a leitura de um docente de E/LE que teve na sua formação e na sua atividade profissional um contato maior com a língua formal. Nesse contexto, escolhemos o blog como o suporte virtual dos textos a serem lidos pelo sujeito por apresentar uma linguagem mais coloquial. No que se refere ao aporte teórico, esta pesquisa tem com principais bases a Linguística Textual (KOCH, 2009, 2002, 2007; KOCH ; TRAVAGLIA, 1996, 2000) e a leitura sócio-interacional (KATO, 1986, 2007; KLEIMAN, 1993, 1996, 2008; NUNES, 2005; VERGNANO-JUNGER, 2009). Também utilizamos alguns elementos da Análise do Discurso de base enunciativa em pontos nos quais ela dialoga com a perspectiva sócio-interacional, como, por exemplo, na noção de gênero do discurso (MAINGUENEAU, 1996, 2003; BAKTHIN, 2003). A Sociolinguística (MORENO FERNANDÉZ, 1996; ALKMIN, 2001) contribuiu para estabelecer os parâmetros da língua coloquial e formal. Quanto à leitura em ambiente virtual, seguimos Ribeiro (2005), Marcuschi (2007), Santaella (2008) e Vergnano-Junger (2009). Para a elaboração deste trabalho, utilizamos uma metodologia híbrida composta de uma parte documental e de um estudo de caso. A fase documental teve como metas classificar os blogs de docentes de E/LE e selecionar dois para a elaboração de atividades de leitura guiada. O estudo de caso realizado com um docente de E/LE, por sua vez, teve como etapas uma leitura livre, duas guiadas e uma entrevista. Objetivou observar e discutir o perfil e o processo leitor do sujeito, com foco na intervenção de elementos linguísticos. Dos resultados obtidos, podemos destacar uma proposta de classificação dos blogs de professores de E/LE. Com base no estudo de caso, duas considerações merecem destaque: (a) uma maior dificuldade de leitura do texto coloquial, ao que tudo indica, gerada pela variedade lexical e (b) uma tendência do sujeito à leitura linear em ambiente virtual, com atenção voltada, frequentemente, para os aspectos de vocabulário e como esses afetavam a compreensão, demonstrando uma tendência à leitura decodificadora

A high-speed image sensing technique with adjustable frame rate based on an ordinary CCD

In the sinusoidal phase modulating interferometer technique, the high-speed CCD is necessary to detect the interference signals. The reason of ordinary CCD's low frame rate was analyzed, and a novel high-speed image sensing technique with adjustable frame rate based on ail ordinary CCD was proposed. And the principle of the image sensor was analyzed. When the maximum frequency and channel bandwidth were constant, a custom high-speed sensor was designed by using the ordinary CCD under the control of the special driving circuit. The frame rate of the ordinary CCD has been enhanced by controlling the number of pixels of every frame; therefore, the ordinary of CCD can be used as the high frame rate image sensor with small amount of pixels. The multi-output high-speed image sensor has the deficiencies of low accuracy, and high cost, while the high-speed image senor with small number of pixels by using this technique can overcome theses faults. The light intensity varying with time was measured by using the image sensor. The frame rate was LIP to 1600 frame per second (f/s), and the size of every frame and the frame rate were adjustable. The correlation coefficient between the measurement result and the standard values were higher than 0.98026, and the relative error was lower than 0.53%. The experimental results show that this sensor is fit to the measurements of sinusoidal phase modulating interferometer technique. (c) 2007 Elsevier GmbH. All rights reserved.

Geodiversidad de la franja litoral Deba-Zumaia. Un paseo geológico virtual

El tramo litoral entre Deba y Zumaia constituye una de las zonas más conocidas y mejor estudiadas de todo el ámbito geológico de los Pirineos y, más particularmente, de su porción más occidental: la denominada cuenca o Región Vasco Cantábrica. Tal circunstancia deriva de los atributos particulares de su registro geológico: un potente conjunto de rocas sedimentarias de persistente estratificación, formadas en un antiguo fondo marino que, a pesar de grandes semejanzas, era muy distinto a los fondos marinos actuales. A este potente conjunto de rocas sedimentarias se le conoce bajo la denominación genérica de “flysch”, término de amplia raigambre geológica, cuya concepción y uso han cambiado considerablemente con el tiempo y el avance del conocimiento.

Detection of Brillouin scattering temperature signal in Brillouin optical time-domain reflectometer sensing system based on instantaneous frequency measurement technology

We present a simple and practical method for the single-ended distributed fiber temperature measurements using microwave (11-GHz) coherent detection and the instantaneous frequency measurement (IFM) technique to detect spontaneous Brillouin backscattered signal in which a specially designed rf bandpass filter at 11 GHz is used as a frequency discriminator to transform frequency shift to intensity fluctuation. A Brillouin temperature signal can be obtained at 11 GHz over a sensing length of 10 km. The power sensitivity dependence on temperature induced by frequency shift is measured as 2.66%/K. (c) 2007 Society of Photo-Optical Instrumentation Engineers.

Detection of Brillouin scattering temperature signal in Brillouin optical time-domain reflectometer sensing system based on instantaneous frequency measurement technology

abstract {We present a simple and practical method for the single-ended distributed fiber temperature measurements using microwave (11-GHz) coherent detection and the instantaneous frequency measurement (IFM) technique to detect spontaneous Brillouin backscattered signal in which a specially designed rf bandpass filter at 11 GHz is used as a frequency discriminator to transform frequency shift to intensity fluctuation. A Brillouin temperature signal can be obtained at 11 GHz over a sensing length of 10 km. The power sensitivity dependence on temperature induced by frequency shift is measured as 2.66%/K. © 2007 Society of Photo-Optical Instrumentation Engineers.}

Preparation, characterization and gas sensing properties of high soluble metal (II) phthalocyanine thin films by spin-coating method

Three novel metal (II) phthalocyanine complexes were synthesized by cyclic tetramerisation reaction of a dicyano benzene component and different metal ions (Pd2+, Co2+, Zn2+). The structure of complexes was confirmed by elemental analysis, mass and IR spectrum. The excellent solubility of the complexes in benzene enabled us to obtain films by a spin-coating method. The films were characterized by IR, electronic spectral and AFM. The gas sensing properties to NO2 of the metal (II) phthalocyanine complex films were studied. In addition, the effects of different metal ions and the gas sensing temperature on the sensing properties were studied. (C) 2005 Elsevier B.V. All rights reserved.

Effects of sensing temperature on the NO2-sensing properties of octa-iso-pentyloxymetallonaphthalocyanine spin-coated films

A kind of 1,6,10,15,19,24,28,33-octa-iso-pentyloxy-2,3-metallonaphthalocyanines complexes MNc(iso-PeO)(8) (M = Co, Cu, Pd) are used as spincoating film-forming materials. The surface morphologies of the films prepared were studied first. These films were then used for the experiments of NO2 sensing. The effects of sensing temperature as well as the NO concentration on the sensing properties were studied. The experimental results showed that the three MNc(iso-PeO)(8) films were uniform, smooth and dense. Due to the different metal ions (M) on the center of naphthalocyanine, the CoNc(iso-PeO)(8) film had a higher film resistance and response-recovery rate in the NO2 sensing experiments. On the contrary, the response to NO2 of the PdNc(iso-PeO)(8) and CuNc(iso-PeO)(8) films were superior to that of CoNc(iso-PeO)(8). By varying the sensing temperature, it was found that the elevation of sensing temperature could improve the sensing response, recovery ratio, and sensitivity of the sensing films. At high concentrations of NO2, the response time became shorter. (c) 2007 Elsevier B.V. All rights reserved.

Preparation, characterization and gas sensing properties of lead tetra-(tert-butyl)-5,10,1 5,20-tetraazaporphyrin spin-coating films

A spin-coated film of lead tetra-(tert-butyl)-5,10,15,20-tetraazaporphyrin complex (PbTAP(t-Bu)(4)) was obtained and characterized by IR spectra, absorption spectra and atomic force microscopy. The response and recovery characteristics of the film to NH3, NO2 and C2H5OH vapor were investigated at room temperature. In addition, the reversibility and stability of the film to NH3 were also studied. The results indicate that the PbTAP(t-Bu)(4) derivative can be exploited as an NH3 sensor at room temperature. (c) 2007 Elsevier B.V. All rights reserved.

Preparation, characterization and gas sensing properties of nickel octa-iso-pentyloxynaphthalocyanine spin-coating films

Spin-coated films of nickel 1,6,10,15,19,24,28,33-octa-iso-pentyloxy-2,3-naphthalocyanine complex were obtained and characterized by UV-vis absorption spectroscopy. A linear relationship between the absorbance and solution concentration was observed. Low concentration solutions could afford smooth and homogeneous film surfaces as indicated by atomic force microscopy. The film structure was studied by small angle X-ray diffraction. The films were used for NO2 sensing experiments. The results indicate that the elevation of sensing temperature can shorten the response time and increase recovery ratio and response magnitude of the sensing films. High NO2 concentration can also shorten response time. (C) 2008 Elsevier B.V. All rights reserved.

Modular integration and on-chip sensing approaches for tunable fluid control polymer microdevices

228 p.