18 research outputs found

    Design and analysis of high performance low noise oscillators and phase lock loops

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    The design and implementation of high purity, high speed and power efficient clock generation Integrated Circuits continue to be one the greatest challenges facing IC designers today. In order to address this challenge, this thesis considers the modeling and design of two fundamental clock generation circuits – the VCO and PLL.An improved ring oscillator topology is proposed which has the advantage of an ultra wide tuning range. A novel noise aware ring oscillator model is also proposed which links the noise performance of the oscillator to its transistor dimensions giving insight to the design procedure. The use of this VCO model in a noise-aware PLL model allows the trade-off between noise performance and the loop bandwidth to be quantified accurately. From further analysis of the proposed PLL model, a novel PLL structure has been designed which is extremely successful at reference spur suppression.Simulation results based on the proposed model and foundry BSIM3v3 models are provided for all the VCO and PLL designs. To validate the proposed VCO topology and VCO model, two prototype chips have been fabricated and measured results show close agreement with theoretical analysis and simulatio

    Recombinant expression of fungal oxidases for industrial application

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    Laccases catalyse the oxidation of a range of organic substrates coupled to the reduction of molecular oxygen to water. They are members of the ubiquitous blue multi-copper oxidase family. These enzymes are implicated in a wide variety of biological activities. Most of the laccases studied thus far are of fungal origin. Large variety of potential substrates has raised interest in the use of laccases in several industrial applications, such as pulp delignification, textile dye bleaching, effluent detoxification, biopolymer modification and bioremediation. Cloning of the laccase genes followed by heterologous expression may provide higher enzyme yields and may permit to produce laccases with desired properties (different substrate specificities and improved stabilities) for industrial applications. Heterologous expression of Pleurotus ostreatus laccases POXC and POXA1b in two yeasts and a first approach of directed evolution experiments are reported. The yeasts of choice were Saccharomyces cerevisiae, proven to be success-full in recombinant laccase expression and directed-evolution experiments, and Kluyveromyces lactis, a non-conventional yeast offering significant advantages, such as high-level secretion of non-hyperglycosylated recombinant proteins. Expression vectors were set up cloning the cDNAs under the control of different promoters. Furthermore, the laccase leader peptides (poxc and poxa1b), as well as the yeast derived signal peptides (S. cerevisiae invertase and K. lactis killer toxin), were alternatively used to direct the secretion of active laccase into the culture medium. The laccase signals proved to be more effective to drive the secretion of recombinant proteins in both hosts. Levels of laccase secreted activity were markedly different: rPOXA1b transformants always gave much higher activity than rPOXC transformants, and production of both laccases in S. cerevisiae was significantly lower than that in K. lactis. Recombinant laccases from K. lactis were purified to electrophoretic homogeneity and characterized. rPOXA1b specific activity was similar to that of the native protein, whilst rPOXC specific activity was much lower than that of the native POXC. Mass spectrometry analyses of the recombinant proteins allowed to verify their primary structures and to identify post-translational modifications. Our data confirm that K. lactis has a lower tendency, respect to S. cerevisiae, to hyperglycosylate recombinant proteins. The S. cerevisiae laccase expression systems were further used to set off directed evolution experiments. Mutated cDNAs libraries with different mutation rate were created, and homologous recombination experiments were performed, giving rise to libraries of mutated laccase secreting yeasts. Moreover a screening procedure to isolate clones exhibiting desired property was realized. As a result, this work allowed obtaining the heterologous expression of two P. ostreatus laccases in yeasts, and their purification and characterisation. Moreover, this research work broadened the potentiality of the developed expression system addressing enzymes to such large markets and different industrial application such as pulp and textile bleaching, and enzymatic remediation of waste streams. A new laccase host (K. lactis) has been built on, and its promising performances will lead to further investigate its utilization for further structure-activities studies, as well as for directed evolution. Results obtained demonstrate the potential of the recombinant expression for the study of potential industrial interest

    Desenvolvimento de um dosímetro in vivo a MOSFET para aplicações em radioterapia

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    Tese (doutorado) - Universidade Federal de Santa Catarina, Centro Tecnológico, Programa de Pós-Graduação em Engenharia Elétrica, Florianópolis, 2013.Na radioterapia (teleterapia), a diferença entre a dose prescrita e a dose recebida pelo paciente deve ser de no máximo 5%. Por esta razão o uso de dosímetros é essencial para atingir esta especificação e garantir o sucesso deste tipo de tratamento contra o câncer. Neste trabalho é apresentado um dosímetro in vivo a MOSFET para aplicações radioterápicas que possui um processo de leitura simples e preciso e que utiliza um sensor pequeno e de baixo custo. Além disso, este dosímetro não requer cabos ou baterias durante a irradiação o que é vantajoso, pois os metais presentes nestes componentes interagem com a radiação podendo assim alterar o valor da dose recebida pelo paciente. No dosímetro desenvolvido foi utilizado o circuito integrado (CI) CD4007UBM (Texas Instruments) como sensor de radiação. A sua escolha é justificada, pois seus transistores MOS possuem um óxido de porta com espessura de 120nm. Esta espessura é indicada para a aplicação desejada, pois tem uma sensibilidade à radiação ionizante próxima de 7 mV/Gy e permite a operação com tensões relativamente baixas, |VT| 1,6 V. Além disso, este CI é de muito baixo custo (R1/CI)epossuidimenso~esreduzidas(aˊreade35mm2eespessurainferiora2mm).EmumdosıˊmetroaMOSFETadosetotaleˊinferidapelavariac\ca~odatensa~odelimiar(VT)devidoaˋradiac\ca~oionizante,destemodoocircuitoextratordeVTeˊumblocofundamentaldestetipodedosıˊmetro.Nodosıˊmetrodesenvolvidofoiutilizadoumcircuitoextratorcomcorrenteconstante(CC)preciso,combaixoconsumoequedeterminadiretamenteovalordeVT.EˊimportantemencionarqueesteextratorCCoperanainversa~omoderada(enquantoextratoresCCconvencionaissa~opolarizadosnainversa~oforte)eextraiumvalordeVTquepossuisignificadofıˊsico.Osexperimentoscomradiac\ca~oionizanteforamrealizadosnoCentrodePesquisasOncoloˊgicas(CEPON)emFlorianoˊpolisutilizandoaceleradoreslinearesparagerarraiosXde6MVe15MV.DentreosprincipaisresultadosdoprotoˊtipododosıˊmetroMOSFETCD4007podemoscitar:sensibilidadede98,1mV/Gy,depende^nciateˊrmicade0,5cGy/°C,depende^nciaangularde131/CI) e possui dimensões reduzidas (área de 35mm2 e espessura inferior a 2 mm). Em um dosímetro a MOSFET a dose total é inferida pela variação da tensão de limiar (VT) devido à radiação ionizante, deste modo o circuito extrator de VT é um bloco fundamental deste tipo de dosímetro. No dosímetro desenvolvido foi utilizado um circuito extrator com corrente constante (CC) preciso, com baixo consumo e que determina diretamente o valor de VT. É importante mencionar que este extrator CC opera na inversão moderada (enquanto extratores CC convencionais são polarizados na inversão forte) e extrai um valor de VT que possui significado físico. Os experimentos com radiação ionizante foram realizados no Centro de Pesquisas Oncológicas (CEPON) em Florianópolis utilizando aceleradores lineares para gerar raios-X de 6 MV e 15 MV. Dentre os principais resultados do protótipo do dosímetro MOSFET CD4007 podemos citar: sensibilidade de 98,1 mV/Gy, dependência térmica de 0,5 cGy/°C, dependência angular de 13%, dependência energética de 1,3%, linearidade de 97,5% e atenuação ao feixe de apenas 0,14%.Abstract : In radiotherapy (teletherapy), the maximum difference between the prescribed dose and the dose delivered to the patient must be ±5%. For this reason, the use of dosimeters is essential to meet this specification and, consequently, to ensure the success of this type of cancer treatment. In this work we present a new in vivo MOSFET dosimeter suitable for in vivo radiotherapy applications which combines a simple and accurate readout procedure with a small size, low-cost, and cable/battery-free sensor. The absence of cable and battery during irradiation is interesting because metals that are present in these components can deflect radiation and, consequently, change the dose received by the patient. The dosimeter that we developed uses the integrated circuit (IC) CD4007UBM (Texas Instruments) as the radiation sensor. This IC was chosen because its MOS transistors have a gate oxide thickness of 120 nm, which is indicated for the desired application since it has adequate radiation sensitivity (7 mV/Gy) and is able to operate at relatively low voltage (|VT | ~= 1,6 V). Moreover, this IC has a very low cost, US0.5/IC, and small dimensions (35 mm2 and thickness lower than 2 mm). MOSFET dosimeters sense the total dose by the variation of the threshold voltage (VT ) due to ionizing radiation; for this reason, the VT -extractor circuit is a fundamental block in this type of dosimeter. In our dosimeter we used an accurate and lowpower constant-current (CC) VT -extractor circuit that directly determines the VT . It is worth to mention that this CC extractor operates in moderate inversion (conventional CC extractors are biased in strong inversion) and extracts a value of VT that has physical meaning. Experiments with ionizing radiation were carried out at the Centro de Pesquisas Oncol´ogicas (CEPON) in Florian´opolis/Santa Catarina using linear accelerators to generate X rays of 6 MV and 15 MV. Among the main results of the CD4007 MOSFET dosimeter we can highlight: radiation sensitivity 98.1 mV/Gy, thermal dependence 0.5 cGy/?C, angular dependence of 13%, energy dependence of 1.3%, linearity of 97.5%, and attenuation to the radiation beam of 0.14%

    Impedance spectroscopy for cellular and biomolecular analysis

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    The application of microfabrication technology to molecular and cell biology has motivated the rapid development of a novel class of microdevices collectively known as ‘Lab On a Chip’ devices.Impedance spectroscopy is a non-invasive, label-free, analytical technique that is amenable to miniaturization, electronic integration, automation, and scalability within ‘LOC’ devices.This thesis describes a microfabricated device for performing continuous impedance analysis of individual cells held in an array of hydrodynamic traps. This device enables continuous long-term analysis of cells and time-dependent measurement of changes elicited by cytotoxic agents and drug compounds. Finite element models are employed to predict the response to changes in the captured single cells (cell position in the trap, cell size, membrane conductivity). The system is used to assay the response of HeLa cells to the effects of the surfactant Tween 20 and Streptolysin-O, a bacterial pore-forming toxin.Novel electrode materials that reduce the parasitic effect of electrode polarisation are described and characterised. These are iridium oxide and PPy/PSS (polypyrrole/poly(styrenesulphonate)). Impedance data is analysed in terms of equivalent circuit models. The findings presented suggest that iridium oxide and PPy/PSS could be used as alternative materials to platinum black and plain platinum. PPy/PSS electrodes offer the highest electrode/electrolyte interface area and least variation with time.Finally, a silicon-based capacitive sensor with nanometric plate separation (nanogap capacitor), is characterized by impedance spectroscopy, and used to explore the behaviour of double layers constrained in cavities of dimensions comparable to the Debye length
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