Dissertations / Theses on the topic 'Ion-sensitive'

Ion sensitive organic field-effect transistors (ISOFETs) with a metal–oxide–semiconductor field-effect transistor (MOSFET) architecture have been fabricated by using poly(3-hexylthiophene) (P3HT) and poly(methyl methacrylate) (PMMA) as the semiconductor and dielectric layers, respectively. To avoid any pin-holes in the dielectric layer, the ISOFET was coated by two separate PMMA layers. An Ag/AgCl double-junction reference electrode was used as the gate. The results show that the uncoated ISOFET exhibited transistor behaviour in aqueous solutions. However, these devices possessed a small sensitivity of about 0.5 nA dec-1 to H+, K+ and Na+ ions. Langmuir-Blodgett membranes were then used to improve the ISOFET response to the target ions in solution. By coating the gate dielectric (PMMA) with an LB membrane of pure arachidic acid (AA), the ISOFETs showed a significantly higher sensitivity to H+ ions of about 3.5 nA pH-1, but no improvement in the pK response (< 0.5 nA dec-1). The compact ionised layers of carboxylic acid head groups were thought to lead to the improvement in the pH sensitivity; however, the layers of long hydrocarbon chains prevented large monovalent ions, such as K+ and Na+, from interacting with the ionised carboxylic acid head groups. ISOFETs coated with an arachidic acid/valinomycin (AA/val) mixture did not show any selectivity to K+ ions, but exhibited enhanced sensitivities to both K+ and Na+ ions. Instead of trapping K+ ions, the valinomycin molecules in the AA membrane were thought to disrupt the membrane architecture and provide ion-leakage channels. Pure valinomycin-coated ISOFETs also revealed enhancements in both sensitivity and selectivity to K+ ions over Na+. This may be due to the fact that the cavity in the valinomycin molecules can accommodate a K+ ion but not a Na+ ion. To study facilitated K+ transport across the membrane, LB films of AA/val mixture and pure valinomycin were coated on porous supports. The responses of both uncoated and coated membranes were similar. After deposition, collapse of the LB film into the pores may provide leakage channels. This probably led to the observed gradual decrease of the potentials across the membranes.

There have been a number of attempts since the inception of the glass electrode to replace the internal filling solution with a solid state form of contact. These have included both metallic and non-metallic materials. In the present work such contacts are reviewed, the nature of the materials, and conduction mechanisms between the contact and glass are discussed. Noble metal contacts alone are not expected to give a reproducible performance because of the lack of a common charge carrier which would allow conduction across the interface. However insertion of a non-metallic transition material which contains charge carriers common to both metal and glass may lead to more predictable performance. The materials, sodium tungsten bronze, iron-aluminium-sodium silicate glass, and various silver salts were interposed between a metal conductor and ion sensitive glass. Potentiometric measurements were made to determine sensitivity and time dependence of the output potential. These revealed that both the sodium tungsten bronze and iron-aluminium-sodium silicate glass gave improved performance over noble metal contacts. The silver salt contacts gave variable performance but it was shown that composite silver salts led to greater predictability of the value of the potential. Spectroscopic measurements were made to allow association of the observed concentration changes at the interface with potentiometric data and contribute to elucidation of reaction mechanisms. It was possible to relate the observed potential changes for silver halides with the increase in silver metal content in the halide layer. Interfacial conduction mechanisms remain unclear but charge transfer is most likely to occur through ionic conduction of sodium or silver ions across the interface. Sodium containing contacts, particularly iron-aluminium-sodium silicate glass, appeared to give a more stable output potential than silver containing contacts. Fabrication of an all-solid-state glass electrode from the former class of materials may be both simpler and more likely to achieve a reliable sensor than from the latter.

Transistores de Efeito de Campo Sensíveis a Íons (ISFETs) revolucionaram a tecnologia de sensores químicos e de pH por serem pequenos e compatíveis com tecnologias de microfabricação em grande escala. Nós desenvolvemos uma metodologia para fabricar e caracterizar sensores ISFET para medida de pH no laboratório de microeletrônica da UFRGS. Sensores ISFET do tipo NMOS com camadas de silica e alumina foram fabricados com tecnologa CMOS padrão. Transistores de W=1000 m e L=10 m foram fabricados em conjunto para monitorar o processo de fabricação através de medidas de Capacitância- Tensão (C-V) e Corrente-Tensão (I-V). Os dispositivos foram colados em suportes de circuito impresso, manualmente microsoldados e encapsulados com cola epoxy. Com o dispotivo na ponta, o suporte foi conectado a um Analisador de Parâmetros de Semicondutores em conjunto com um eletrodo de referência comercial de Ag/AgCl e imersos em soluções de pH diferente para a realização de medidas de pH. A sensibilidade à variação de pH, definida como a variação na tensão de limiar devido a presença do eletrólito, para os sensores de silica foi de 30mV/pH em ácidos e 24mV/pH para bases. Sensores de alumina tiveram uma performance muito superior e exibiram sensibilidade de 32mV/pH em ácidos e 48mV/pH em bases. A tecnologia de fabricação e o conhecimento experimental desenvolvidos nesse trabalho fornecem uma fundação essencial para projetos de pesquisa locais que buscam a aplicação de sensores de estado sólido no sensoriamento de sistemas químicos ou biológicos.

Polymer gels could be used as chemical and biological sensors should the technology to measure their volume change in response to analytes be fully developed. Optical approaches based on thin films, synthetic opals, inverse opals and holographic sensors offer the opportunity to allow colorimetric analysis of polymer gel swelling. The diffraction from a holographic sensor with primary amine functionalities was found to be narrow band in wavelength, 15 nm, and angle, 0.7°, and the presence of side-lobes on the spectra were explained in terms of coupled wave theory. During pH-jump induced volume change the diffraction spectra from the holographic sensor developed crenulations which were dependent on hologram thickness and observation angle but largely independent of buffer strength. Through analysis of the kinetics and spectra an integrated model based on Crick’s solution for diffusion into a thin film could explain both the sigmoidal kinetics observed, and the spectral crenulations. The model described the initial rapid progress of an ionisation front moving through the gel, followed by the slow diffusion of analyte in a longer second phase. A panel of polymers containing primary amines and the carbonate ionophore trifluoroacetylbenzoate (TFAB) in poly(2-hydroxyethyl methacrylate). (pHEMA) and polyacrylamide (pAAm) copolymers was produced. Their response in relation to temperature, ionic strength, sulfate and aqueous carbon dioxide was examined. It was found that temperature responsive was a good indication of response to analytes. Which may, in-part, be due to the dominance of polymer-solvent mixing terms in determining response at high ionic strength. pHEMA holograms were insensitive to the identity and valency of the ions and pAAm was responsive to these conditions as determined by the relative “salting-out” potential of the ions. However, almost in contradiction to this trend, the influence of ionic strength was ten times lower on pAAm relative to pHEMA. The sensitivity to specific ions and the relative insensitivity of pAAm holograms suggest that pHEMA may have more potential as a basis for holographic sensors.

The avermectins (ivermectin, doramectin etc) and milbemycins are effective anthelmintics used widely in animal and human medicine for the past twenty years. The actual site of action of the avermectins on the GluCl is unclear, but binding studies have concluded that it does not share a binding site with glutamate. The GluCl channels have been well characterised in Caenorhabditis elegans and are beginning to be characterised in parasitic nematode species such as Haemonchus contortus, Dirofilaria immitis and Cooperia oncophora. The aim of this project was to characterise the H. contortus GluClα3B subunit and its interactions with agonists, glutamate and ivermectin using electrophysiology to study Xenopus oocytes expressing GluClα3B homomeric channels and ligand binding studies on COS-7 cells expressing the subunits. Site–directed mutagenesis was used to introduce resistance associated candidate polymorphisms into the H. contortus GluClα3B subunit. The effects of these changes on the response to glutamate and ivermectin were assessed. One mutation found in IVR C. oncophora, L256F, confers a 3-fold loss of sensitivity to glutamate and a 6.5 fold loss of sensitivity to IVM. This mutation is found in the C-terminal area of the extracellular region of the channel and, from homology modelling, we know it lies in close proximity and possibly interferes with another candidate mutation V235A, and the Cysteine residue at position 192 which forms one side of the structurally significant disulphide bridge. Further introduction of different mutations at this position showed the larger the substituted amino acid, the greater the effect on IVM sensitivity. Another amino acid substitution (T300S) results in the prohibition of a functional channel. The protein is produced and is able to bind IVM with high affinity but does not create a functional channel. These data show that polymorphisms found in field isolates of parasites can have a significant effect on GluCl channels and may contribute to drug resistance.

In this thesis, the role of transient receptor potential vanilloid 4 (TRPV4) in mechanical hyperalgesia induced by inflammatory mediators and second-messenger pathways was investigated. The hypotonicity-activated [Ca²⁺]_I increase in HEK293 cells transiently expressing TRPV4 was greatly enhanced after exposure to the PKC activator phorbol 12-myristate 13-acetate (PMA). The sensitization was significantly reduced in the presence of kinase inhibitors, including staurosporine, BIM, and rottlerin, suggesting that a PKC-mediated phosphorylation was involved, and could be PKCδ mediated. The sensitization induced by PMA was also significantly reduced by the mutation S162A/T175A/S189A. The phosphorylation level of TRPV4 was greatly enhanced with PMA treatment, and was significantly decreased by the application of the PKCδ-specific inhibitor rottlerin or with the mutant S162A/T175A/S189A. These results suggest that sensitization was mediated by phosphorylation by PKCδ of S162, T175 and S189. The hypotonicity-activated [Ca²⁺]_i increase mediated by TRPV4 was enhanced after exposure to the cAMP activator forskolin (FSK). The sensitization was prevented in the presence of the selective PKA inhibitor H89. The sensitization induced by FSK was significantly reduced by the mutant S824A. The A kinase anchoring protein (AKAP) family is known to assemble a wide range of kinases, including PKA and PKC, into signalling complexes with appropriate targets. Functional studies using calcium imaging showed that AKAP79 overexpression enhanced sensitization of TRPV4 by FSK and PMA, while downregulation of AKAP79 using siRNA inhibited sensitization. TRPV4 coexpression with AKAP79 enhanced the phosphorylation induced by PMA, and the phosphorylation level significantly decreased in cells coexpressing TRPV4 and siRNA AKAP79. AKAP79 may be a critical component converging the effects of PKC and PKA on TRPV4.

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2013.
Cataloged from PDF version of thesis.
Includes bibliographical references (pages [47]-53).
Following successful demonstrations of quantum algorithms and error correction with a handful of trapped ions in a macroscopic, machined Paul trap, there is a growing effort to move towards microfabricated traps with all the electrodes on a single chip. These traps, known as surface-electrode ion traps, are more amenable to being shrunk in size and replicated, or integrated with optical components and electronic devices. However, in the shift towards surface-electrode traps, and as traps are miniaturized in general, laser beams are brought closer to electrode surfaces, exacerbating laser-induced charging. Because of their charge, trapped ions are extremely sensitive to stray charges that accumulate on the trap surface. The DC potentials caused by stray charge displace the ion from the null of the RF trapping field, resulting in a fast, driven motion of the ion (known as micromotion) which hinders quantum operations by broadening transitions and causing decoherence. In a surface trap, micromotion detection is difficult as the laser beams used for measurement typically cannot crash into the trap, obscuring ion offsets out of the trap plane. Existing methods for micromotion detection permit ion positioning accurate to the ground state wavepacket size (of order 10 nm), but cannot identify ion offsets out of the trap plane with the same accuracy. Schemes for sensitive compensation often have restrictive requirements such as access to a narrow atomic transition. We introduce a new approach, which permits out-of-plane micromotion compensation to within 10s of nanometers with minimal overhead. Our technique synchronously detects ion excitation along the trap axes when it is driven by secular-frequency sidebands added to the RF electrodes; the excitation amplitude is proportional to the offset from the RF null. We make a detailed theoretical comparison with other techniques for micromotion compensation and demonstrate our technique experimentally.
by Amira M. Eltony.
S.M.

This thesis, after a review on the state-of-the-art sequencing and genotyping technologies, focuses on the semiconductor-based systems using pH change for DNA (Deoxyribonucleic acid) detection by ion-sensitive feld effect transistors (ISFETs). Accuracy and throughput, besides cost, are the key concerns in these systems, which are reflected on their signal-to-noise ratio and ability to process enormous measurement data at low levels for base-calling. Simulations are provided on the signal behaviour, supported by the literature review. The ISFETs have been investigated for their dimension and shape (single-plate vs mesh, and square vs octagonal). More complete formula and design methodology (to suppress the process variations and signal drift) have been provided for the ISFET operation by including the coupling effect. The experiment results, on 8 dies each containing 15 devices, showed the decoupling parasitics dependency on the sensing area perimeter. A buffer-shield structure has been proposed to improve the ISFET coupling. In addition, based on the ISFET drift analysis, measuring the biasing reference electrode current is recommended for the drift direction monitoring/prediction. Considering the two main applications of sequencing and genotyping, new readout configurations have been proposed to enhance the on-chip signal processing. Piecewise linear approximating (PLA), and temperature-insensitive continuous-time ΔpH to digital converter (TICTC), tackle the ISFET and temperature dependency. The TICTC has been designed for a resolution of 0.015pH, easily scalable and only dependent on the relative aspect ratio of its current mirrors. Its dynamic range is not limited despite operating in weak inversion. For very large-scale sequencing arrays, common-mode noise elimination using the back-gate has been proposed. It allows on-chip suppression of the background noise in the sequencing microchips, reducing the low-level processing load. Moreover, a pseudo-inverter-based readout has been designed that may allow improving the conversion resolution by current-mode comparison and indirect feedback to the ISFET gate.

In the late 1980s Carver Mead introduced Neuromorphic engineering in which various aspects of the neural systems of the body were modelled using VLSI1 circuits. As a result most bio-inspired systems to date concentrate on modelling the electrical behaviour of neural systems such as the eyes, ears and brain. The reality is however that biological systems rely on chemical as well as electrical principles in order to function. This thesis introduces chemical bionics in which the chemically-dependent physiology of specific cells in the body is implemented for the development of novel bio-inspired therapeutic devices. The glucose dependent pancreatic beta cell is shown to be one such cell, that is designed and fabricated to form the first silicon metabolic cell. By replicating the bursting behaviour of biological beta cells, which respond to changes in blood glucose, a bio-inspired prosthetic for glucose homeostasis of Type I diabetes is demonstrated. To compliment this, research to further develop the Ion Sensitive Field Effect Transistor (ISFET) on unmodified CMOS is also presented for use as a monolithic sensor for chemical bionic systems. Problems arising by using the native passivation of CMOS as a sensing surface are described and methods of compensation are presented. A model for the operation of the device in weak inversion is also proposed for exploitation of its physical primitives to make novel monolithic solutions. Functional implementations in various technologies is also detailed to allow future implementations chemical bionic circuits. Finally the ISFET integrate and fire neuron, which is the first of its kind, is presented to be used as a chemical based building block for many existing neuromorphic circuits. As an example of this a chemical imager is described for spatio-temporal monitoring of chemical species and an acid base discriminator for monitoring changes in concentration around a fixed threshold is also proposed.

Orientadores: Jacobus W. Swart, Edgar Charry Rodriguez
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Eletrica
Made available in DSpace on 2018-07-21T13:54:41Z (GMT). No. of bitstreams: 1 ChavezPorras_Fernando_M.pdf: 7348729 bytes, checksum: 99e9c30ec2191af662ee58af3b56feb0 (MD5) Previous issue date: 1996
Resumo: Neste trabalho é primeiro apresentada uma nova classificação dos sensores eletroquímicos, objetivando fazer um paralelo entre os sensores eletroquímicos convencionais e a crescente geração de sensores eletroquímicos microeletrônicos, ou aqueles fabricados com técnicas de fabricação de circuitos integrados. Em seguida, são apresentados alguns resultados práticos relacionados com o desenvolvimento de um sensor coulométrico baseado em ISFETs. Assim, é proposto um esquema de medida conformado por: dois sensores coulométricos conectados em forma diferencial, e por um circuito eletrônico simples que realiza o cálculo do tempo de titulação a partir da segunda derivada da sua respectiva curva de titulação. O desenvolvimento do sistema inclui: a) o projeto e fabricação dos sensores coulométricos, b) o projeto e implementação com circuitos discretos de : um circuito eletrônico para o processamento do sinal de saída dos ISFETs e uma fonte de corrente simples e sua lógica de controle necessária para gerar pulsos de corrente entre 0-15 JlA. O sistema proposto é testado realizando titulações coulométricas de ácido acético, e serve para determinar concentrações de até 0.007 moles/litro usando pulsos de corrente entre 0-15 JlA. Também é apresentado um modelo simples que nos permite comprovar os resultados das medidas. Após é feita uma discussão relacionada com o mecanismo de operação do dispositivo. Finalmente é apresentado o processo de fabricação dos sensores coulométricos, o qual é baseado em um processo de fabricação de ISFETs padrão
Abstract: Firstly, in this work, is showed a new classification of the electrochemical sensors intending to make a paralell between conventional electrochemical sensors and the new generation of electrochemical microelectronic sensors, or that, fabricated with integrated circuits technology. Next, it is showed some practical results related with developing a based on ISFET coulometric sensor. Therefore, it is proposed a measurement set-up conformed by: two coulometric sensors connected in a diferencial way, and an electronic circuit able to compute the titration time from its second derivative of the respective titulation curve. This work involves: a) the design and fabrication of the coulometric sensors, b) the design and implementation with discret circuits of: an electronic circuit for processing the ISFETs output signal and a simple current source and its necessary controllogic able to supply current pulses of 0-15 J.1A. The proposed system is tested doing coulometric titrationof acetic acid, and is able to determine concentrations until 0.007moles/literusing coulometricpulses of 0-15 J.1A. It is also showna simpie model, which corroborate the measurements, and then is given a discussion related with the mechanism of operation of this device. Finally, it is also shown the fabrication process of the coulometric sensors, which is based on a standãrd ISFET fabrication process
Mestrado
Mestre em Engenharia Elétrica

Ligand-gated and ligand-modulated ion channel (IC) sensors have received increased attention for their ability to transduce ligand-binding events into a readily measurable electrical signal. Ligand-binding to an IC modulates the ion flux properties of the channel in label-free manner, often with single-molecule sensitivity and selectivity. As a result, ICs are attractive sensing elements in biosensoring platforms, especially for ligands lacking optical (e.g. fluorescent) or electrochemical properties. Despite the growing number of available ligand-gated and ligand-modulated ICs and artificial lipid bilayer platforms for IC reconstitution, significant work remains in defining the analytical performance capabilities of IC sensors. Particularly, few studies have described platforms for making measurements with rapid temporal resolution and high sensitivity. In this work, we describe an artificial lipid bilayer platform which enables rapid measurement of ion channel activity, a key parameter for developing IC sensors suitable for studying biological events, e.g. single cell exocytosis (Chapter 2 and 3). Additionally, we developed expression, purification, and reconstitution protocols for Kir6.2, a model ligand-gated ion channel, for use in sensor development (Chapter 4). The final goal is to reconstitute ion channel-coupled receptors (ICCRs), G protein-coupled receptor-Kir6.2 fusion proteins, into artificial lipid bilayers to detect small molecules and hormones targeting GPCRs. Towards this goal, we characterized the expression and function of two ICCRs, M2-Kir and D2-Kir, in HEK293 cells (Chapter 5).

Over the last decade, immobilization of proteins onto inorganic materials is becoming more crucial to extend a deep understanding of interaction between proteins and nanoparticles. With understanding of the real interaction lying under the protein-nanoparticle relations, it is possible to organize the conformation and orientation of surface and framework species of nanoparticles to generate ideal surfaces for potential biotechnological applications. Due to their unique properties such as large clean surface, tunable surface properties, adjustable surface charge, and dispersibility in aqueous solutions, zeolite and zeo-type materials are one of the remarkable classes of inorganic materials that are widely studied in the literature. These properties make zeolites promising alternative candidates for the immobilization of enzymes and incorporation into biosensing devices. In the current study, a new approach was developed for direct determination of urea, glucose, and butyrylcholine where zeolites were incorporated to the electrode surfaces of a conductometric biosensor and Ion Sensitive Field Effect Transistors were used to immobilize the enzymes. Biosensor responses, operational stabilities, and storage stabilities of the new approach were compared with results obtained from the standard membrane methods for the same measurements. For this purpose, different surface modification technique, which are simply named as Zeolite Modified Transducers (ZMTs) were compared with Standard Membrane Transducers (SMTs). During the conductometric measurements ZMT electrodes were used, which allowed the direct evaluation of the effect of zeolite morphology on the biosensor responses for the first time. It was seen that silicalite added electrodes lead to increased performances with respect to SMTs. As a result, the zeolite modified urea and glucose biosensors were successfully applied for detecting urea and glucose, which can offer improved possibilities to design biosensors. The results obtained show that zeolites could be used as alternatives for enzyme immobilization in conductometric biosensors development. Furthermore, the sensitivities of urease and butyrylcholinesterase biosensors, prepared by the incorporation of zeolite Beta crystals with varying acidity on the surface of pH-sensitive

The latest experimental results of the multichannel front-end ASIC of TRACE are shown. The device submitted to the foundry in the middle of 2014 and received at the end of the same year has been installed on a dedicated PCB and tested using a pulser. We then designed and realized a preamplifier board with eight ASICs for a total of 32 front channels and one back channel. We connected it to a highly-segmented planar silicon detector and acquired the spectrum of a 241Am-244Cm-239Pu triple alpha source obtaining an overall resolution around 3.5‰. The chip comprises four channels specifically designed for hole signals and one channel for electron signals. The power consumption is around 10 mW per channel as required by the specifications of TRACE. The main design goals are low noise and fast rise time. With proper shaping of the signals this device is capable of producing energy spectra with resolution of approximatively 1 keV. An innovative circuit architecture based on a Time-Over-Threshold technique boosts the dynamic range of the CSP by more than one order of magnitude. The rise time of the leading edge of the signals is fast enough to perform pulse-shape analysis of the waveforms. A peculiar feature of this device is the possibility to easily adjust a host of key parameters through an I2C bus. The bandwidth and sensitivity of the preamplifier can so be optimized according to the experimental needs on a case-by-case basis.

The physical properties of thin nanocrystalline cerium oxide films have been studied with the purpose of their application as a functional material of different microelectronic transducers for biosensors: highperformance photoresistors and photodiodes for bioluminescence registration, ion-selective field-effect transistors (ISFET) and MOS-varactors indicating the pH changes as a result of biochemical processes. The effect of technological factors on the photoelectrical, optical, temperature and electrophysical properties of cerium oxide films has been studied. We established the technological conditions which allow to obtain СеОх-films with desired functional characteristics. On the basis of the synthesized nanocrystalline СеОх-films obtained by the "explosive evaporation" method we developed new types of photodetectors for registration of bioluminescent signal (photoresistors and photodiodes) with enhanced photosensitivity (310- 330 mA/lm∙V) in the visible range. Application of cerium oxide based photoresistors in the bioluminometers instead of photomultiplier tubes and avalanche photodiodes allows to significantly reduce the cost of bioluminometer and increase its sensitivity when measuring at alternating signal. On the basis of nanocrystalline СеОх-films obtained by the "metallic mirrors oxidation" method we developed potentiometric biosensory transducers (ion-selective field-effect transistors and MOS-varactors) with CeOx as gate dielectric. It yields higher sensitivity and stability as compared to the use of the SiO2 and Si3N4 films. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/34964

Thesis (M.S.)--University of Missouri-Columbia, 2007.
The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on April 3, 2009) Includes bibliographical references.

Abstract ACCURATE METHODOLOGY FOR MONITORING BIOMEMBRANE EVENTS By Christine A. Winschel, Ph.D. A Dissertation submitted in partial fulfillment of the requirements for the degree of Doctorate of Philosophy in Chemistry at Virginia Commonwealth University. Virginia Commonwealth University, 2012 Major Director: Dr. Vladimir A. Sidorov ASSOCIATE PROFESSOR, DEPARTMENT OF CHEMISTRY This study describes the synthesis and characterization of a new receptor (cyclen 1) capable of strong selective binding of pyrene-based anionic dyes under near-physiological conditions. This receptor comprises four naphthylthiourea groups tethered to a cyclen core via an ester linkage. The most important finding was the ability of cyclen 1 to bind efficiently to a pH-sensitive pyranine dye, a dye that is commonly used in various biomembrane assays. The high affinity of cyclen 1 to pyranine, its impermeability to the lipid bilayer membrane, fast kinetics of binding, and ability to quench pyranine’s fluorescence were used as a basis for a new membrane leakage assay. This membrane leakage assay is fully compatible with the commonly applied pH-stat transport assay, and therefore it allows for differentiation of ion transport and nonselective leakage mechanisms within a single set of experiments. In the second part of this study a new methodology for the detection of lipid flip was developed. This methodology relies on the quenching of the fluorescence of a newly synthesized cascade-blue-labeled lipid through complex formation with cyclen 1. This receptor-dye complexation also has high affinity for binding at micromolar concentrations and can be reversed by either competitive displacement of the lipid probe or by enzymatic degradation of the receptor leading to the label release and fluorescence dequenching. This new methodology is suitable for the study of lipid flip in both model spherical bilayer membranes and in-vitro experiments, and is less invasive to the model and cell membranes than the commonly utilized 7-nitro-1,2,3-benzoxadiazol-4-yl (NBD)-dithionite methodology. Lastly, new pH-sensitive lipids were synthesized and utilized in the formulation of liposomes suitable for controlled drug release. These liposomes contain various amounts of internal NaCl and undergo internal acidification upon the exogenous addition of an HCl co-transporter in a physiologically relevant NaCl solution. Therefore, acidification ultimately leads to the hydrolysis of the pH-sensitive lipids and subsequent contents release. These liposomes were found to be insensitive to physiological concentrations of human serum albumin and to be non-toxic to cells at concentrations exceeding pharmacological relevance. These results render this new drug release model potentially suitable for in vivo applications.

Honey bees are economically important pollinators of a wide variety of crops that have attracted the attention of both researchers and the public alike due to unusual declines in the numbers of managed colonies in some parts of the world. Viral infections are thought to be a significant factor contributing to these declines, along with exposure to agricultural and apicultural pesticides, but viruses have proven a challenging pathogen to study in a bee model and interactions between viruses and the bee antiviral immune response remain poorly understood. Recent studies have demonstrated an important role for inwardly-rectifying ATP-sensitive potassium (KATP) channels in the cardiac regulation of the fruit fly antiviral immune response, but no information is available on their role in the heart-specific regulation of bee immunity. The results of this work demonstrate that KATP channel modulators have an observable effect on honey bee heart rate that supports their expected physiological role in bee cardiac function. Here, it is also reported that the entomopathogenic flock house virus (FHV) infects adult bees, causing rapid onset of mortality and accumulation of viral RNA. Furthermore, infection-mediated mortality can be altered by pre-exposure to KATP channel modulators. Finally, this work shows that exposure to environmental stressors such as commonly used in-hive acaricides can impact bee cardiac physiology and tolerance to viral infection. These results suggest that KATP channels provide a significant link between cellular metabolism and the antiviral immune response in bees and highlight the significant impact of environmental stressors on pollinator health.
Ph. D.

RESUMO: O corpo carotídeo (CB) é um pequeno órgão sensível a variações na PaO2, PaCO2 e pH. As células tipo I (células glómicas) do corpo carotídeo, as unidades sensoriais deste órgão, libertam neurotransmissores em resposta às variações dos gases arteriais. Estes neurotransmissores atuam quer em recetores pré-sinápticos, localizados nas células tipo I, quer em recetores póssinápticos, localizados nas terminações do nervo do seio carotídeo, ou em ambos. A activação dos recetores pré-sinápticos modula a atividade do corpo carotídeo, enquanto que, a activação dos recetores pós-sinápticos, de carater excitatório, desencadeia um aumento da frequência de descarga das fibras do CSN, com subsequente despolarização dos neurónios do gânglio petroso, e posterior despolarização de um grupo específico de neurónios do centro respiratório central, desencadeando, como resposta final, hiperventilação. Estes recetores pré- e pós-sinápticos podem ser classificados em ionotrópicos ou metabotrópicos, estando os últimos acoplados a adenilatos ciclases transmembranares (tmAC). O mecanismo exato pelo qual as variações dos gases arteriais são detetadas pelo CB não se encontra ainda completamente elucidado, mas tem sido sugerido que alterações nos níveis de cAMP estejam associadas ao mecanismo de deteção de variações de O2 e CO2. Os níveis de cAMP podem ser regulados através da sua via de síntese, mediada por dois tipos de adenilatos ciclases: tmAC sensível aos eurotransmissores e adenilato ciclase solúvel (sAC)sensível a variações de HCO3/CO2, e pela sua via de degradação mediada por fosfodiesterases. A via de degradação do cAMP pode ser manipulada farmacologicamente, funcionando enquanto alvo terapêutico para o tratamento de patologias do foro respiratório (e.g. asma, hipertensão pulmonar, doença pulmonar obstructiva crónica e apneia do sono), que induzem um aumento da actividade do CB.O trabalho descrito nesta dissertação partiu da hipótese de que a actividade do CB é manipulada por fármacos, que interferem com a via de sinalização do cAMP, tendo sido nosso objectivo geral, investigar o papel do cAMP na quimiotransdução do CB de rato, e determinar se a actividade dos enzimas responsáveis pela via de sinalização do cAMP é ou não regulada por variações de O2/CO2. Assim, a relevância deste trabalho é a de estudar e identificar possíveis alvos moleculares (sAC, isoformas de tmAC e PDE) com potencial para serem usados no tratamento de patologias relacionadas com o controlo respiratório. A primeira parte do presente trabalho, centrou-se na caracterização farmacológica da PDE4 no CB e em tecidos não quimiorecetores (e.g. gânglio cervical superior e artérias carótidas), e na observação do efeito de hipóxia aguda na acumulação dos níveis de cAMP, induzidos pelos inibidores de PDE, nestes tecidos. A quantificação de cAMP foi efectuada por técnica imunoenzimática (EIA), tendo sido elaboradas curvas de dose-resposta para os efeitos de inibidores, não específicos (IBMX) e específicos para a PDE2 e PDE4 (EHNA, Rolipram e Ro 20-1724), nos níveis de cAMP acumulados, em situações de normóxia (20%O2/5%CO2) e hipóxia (5%O2/5%CO2). A caracterização das PDE no gânglio cervical superior foi aprofundada, utilizando-se a técnica de transferência de energia de ressonância por fluorescência (FRET) em culturas primárias de neurónios, na presença de inibidores não específicos (IBMX) e específicos para a PDE3 e PDE4 (milrinone e rolipram, respetivamente). Foram igualmente estudadas, através de RT-qPCR, as alterações na expressão de PDE3A-B e PDE4A-D, no gânglio cervical superior, em resposta a diferentes percentagens de oxigénio. Na segunda parte do trabalho investigou-se a via de síntese do cAMP no CB em resposta a variações na concentração de HCO3/CO2. Em concreto, o protocolo experimental centrou-se na caracterização da sAC, dado que a sua actividade é regulada por variações de HCO3/CO2. A caracterização da expressão e regulação da sAC, em resposta a variações de HCO3/CO2 ,foi efectuada no CB e em tecidos não quimioreceptores periféricos (e.g. gânglio cervical superior, petroso e nodoso) por qRT-PCR. A actividade deste enzima foi caracterizada indirectamente através da quantificação dos níveis de cAMP (quantificação por EIA), induzidos por diferentes concentrações de HCO3/CO2, na presença de MDL-12,33-A, um inibidore da tmAC. A expressão das isoformas da tmAC no CB e gânglio petroso foi determinada por RT-qPCR. Adicionalmente, estudámos a contribuição relativa da tmAC e sAC no mecanismo de sensibilidade ao CO2 no CB. Para o efeito foram estudadas as alterações: 1) nos níveis de cAMP (quantificado por EIA) na presença de diferentes concentrações de HCO3/CO2 e ao longo do tempo (5-30 min); 2) na ativação da proteína cinase A (PKA, FRET baseado em sensores) em células tipo I do CB; e 3) na frequência de descarga do CSN (registos) na presença e ausência de ativadores e inibidores da sAC,tmAC e PKA. Por último, foi caracterizada a expressão e actividade da sAC nos quimioreceptors centrais (locus ceruleus, rafe e medula ventro-lateral) através de técnicas de RT-qPCR e EIA. A expressão das isoformas da tmAC foi aprofundada no locus coeruleus através de RT-qPCR. Por fim, comparámos a contribuição da tmAC e sAC nos níveis de cAMP no locus coeruleus em condições de normocapnia e hipercapnia.O nosso trabalho teve os seguintes resultados principais: 1) PDE4 está funcional no corpo carotídeo, artérias carótidas e gânglio cervical superior de rato, embora a PDE2 só se encontre funcional neste último; 2) Os efeitos dos inibidores de PDE nos níveis de acumulação de cAMP foram exacerbados em situações de hipóxia aguda no CB e artérias carótidas, mas foram atenuados no gânglio cervical superior; 3) No gânglio cervical superior, diferentes tipos de células apresentaram uma caracterização específica de PDEs, sugerindo uma subpopulação de células neste gânglio com funções fisiológicas distintas; 4) Embora todas as isoformas de PDE4 e PDE3 estivessem presentes no gânglio, a PDE3a, PDE4b e a PDE4d foram as isoformas mais expressas. Por outro lado, incubações de gânglio cervical superior, em diferentes percentagens de oxigénio, não alteraram (não regularam) significativamente a expressão das diferentes isoformas de PDE neste órgão; 5) a sAC encontra-se expressa e funcional no CB e nos quimiorecetores centrais estudados (locus coeruleus, rafe e medula ventrolateral). A sAC apresenta maior expressão no CB comparativamente aos restantes orgãos estudados, exceptuando os testículos, orgão controlo. Variações de HCO3/CO2 de 0/0 para 24/5 aumentaram os níveis de cAMP no CB e quimiorecetores centrais, tendo sido o aumento mais significativo observado no CB. Concentrações acima dos 24mM HCO3/5%CO2 não induziram alterações nos níveis de cAMP, sugerindo que a actividade da sAC se encontra saturada em condições fisiológicas (normocapnia) e que este enzima não desempenha qualquer papel na deteção de situações de hipercapnia; 6) No CB, a expressão das isoformas tmAC1, tmAC4, tmAC6 e tmAC9 é mais elevada comparativamente à expressão da sAC; 7) Utilizamos diferentes inibidores da tmAC (MDL 12-330A, 500μM, 2’5’-ddADO, 30-300μM, SQ 22536, 200μM) e da sAC (KH7, 10-100μM) para estudar a contribuição relativa destes enzimas na acumulação do cAMP no CB. Tanto a tmAC como a sAC contribuem para a acumulação dos níveis de cAMP em condições de hipercapnia. Contudo, existe um maior efeito destes inibidores nas condições de 12 mM HCO3/2.5%CO2 do que em condições de normocapnia e hipercapnia, sugerindo um papel relevante destes enzimas na atividade do CB em situações de hipocapnia; 8) Não se observaram variações nos níveis de cAMP em resposta a diferentes concentrações de HCO3/CO2 ao longo do tempo (5-30 min). O efeito inibitório induzido por ddADO e KH7 foi sobreponível após 5 ou 30 minutos de incubação em todas as concentrações de HCO3/CO2 estudadas; 9) Por último, verificou-se um aumento na frequência da descarga do nervo do seio carotídeo entre as condições de normocapnia e hipercapnia acídica. Ao contrário do KH7 (10μM), o 2’5’-ddADO reduziu significativamente a frequência de descarga do nervo, quer em condições de normocapnia quer de hipercapnia acídica. Contudo, não se verificou aumento na frequência de descarga do nervo entre normocapnia e hipercapnia isohídrica, sugerindo que a sensibilidade à hipercapnia no CB é mediada por variações de pH. Em conclusão, os resultados decorrentes deste trabalho permitiram demonstrar que, embora os enzimas que medeiam a via de sinalização do cAMP possam ser bons alvos terapêuticos em condições particulares, a sua actividade não é específica para o CB. Os resultados sugerem ainda que o cAMP não é um mediador específico da transdução à hipercapnia neste orgão. Contudo, os nossos resultados demonstraram que os níveis de cAMP são mais elevados em condições fisiológicas, o que sugere que o cAMP possa ter uma função homeostática neste orgão. Por último, o presente trabalho demonstrou que os aumentos de cAMP descritos por outros em condições de hipercapnia, não são observáveis quando o pH se encontra controlado. ------------------ ABSTRACT: The work presented in this dissertation was aimed to establish how specific is cAMP-signaling pathways in the CB mainly in different CO2 conditions and how O2 concentrations alter/drives the manipulation of cAMP signaling in the CB. The experimental studies included in this thesis sought to investigate the role of cAMP in the rat CB chemotransduction mechanisms and to determine whether the enzymes that participate in cAMP signal transduction in the CB are regulated by O2/CO2. We characterized the enzymes involved in the cAMP-signaling pathway in the CB (sAC, tmAC, PDE) under different O2/CO2 conditions. Our results demonstrated that many of these enzymes are involved in CO2/O2 sensing and while they may be useful in treating conditions with alterations in CO2/O2 sensing,they will not be specific to chemoreception within the CB: 1) PDE4 is ubiquitously expressed in CB and non-chemoreceptor related tissues and their affinity to inhibitors change with O2 tensions in both CB and carotid arteries, and 2) sAC and tmAC are expressed in peripheral and central chemo- and non-chemoreceptor tissues and their effect on cAMP levels do not change between normocapnic and isohydric hypercapnic conditions. Our results provide evidence against a specific role of cAMP as a mediator for O2 and CO2 chemotransduction in the rat CB and emphasized the role of pH in CO2 sensitivity of the CB. Furthermore, our results demonstrate that cAMP levels are maintained higher under physiological conditions, supporting recent finding from our lab, which all together suggests that cAMP has a homeostatic function in this organ.

Control of intracellular ion homeostasis is pivotal to plant salt tolerance. Plants have developed a number of mechanisms to keep ions at appropriate concentrations. Both transporters and channels on the plasma membrane play important roles in this function. Plant cyclic nucleotide-gated channels (CNGCs) in the plasma membrane are non-selective monovalent and divalent cation channels. So far, most studies on plant CNGCs have been conducted on heterologous systems. In planta, reverse genetic studies revealed the role of different CNGCs in cation uptake, transport and homeostasis. However, there is little information available about the functional characteristics of plant CNGCs. Among the 20 members of this protein family in Arabidopsis, only AtCNGC2 has been functionally identified as an ion channel; therefore, more functional characterization needs to be done on other members of this protein family. Several CNGCs were suggested to be involved in K+, Ca2+ and Na+ uptake and transport, but available information is scarce. This study investigated the relationship between CNGC10 and ion transport in Arabidopsis, with a particular emphasis on the involvement of CNGC10 in salt tolerance. Arabidopsis thaliana wild type (WT) and two AtCNGC10 antisense lines (A2 and A3) were used to characterise the impact of different level of salt stress on (i) root growth, ion concentration in tissues, ion fluxes across the root surface and intracellular ion concentration and pH at the seedling stage, and (ii) photosynthesis and ion concentration in tissues at the flowering stage. Plants of both antisense lines had higher K+ and lower Ca2+ and Mg2+ concentrations in shoots than WT plants when grown in non-salt control 1/4 Hoagland solution. Altered K+, Ca2+ and Mg2+ internal concentrations in AtCNGC10 antisense lines compared with WT plants under non-salt conditions indicated disturbed long distance ion transport, especially xylem loading/retrieval and/or phloem loading. The results of ion fluxes across the root surface also suggested that AtCNGC10 might be involved in transport of K+, Ca2+ and Mg2+ in tissue. Under sudden salt exposure, higher Na+ efflux and smaller K+ efflux in both antisense lines suggested that AtCNGC10 channels are involved in Na+ and K+ transport. The shoots of AtCNGC10 antisense lines A2 and A3 contained higher Na+ concentrations and significantly higher Na+/K+ ratios compared to WT, resulting in impaired photosynthesis and increased salt sensitivity in A2 and A3 than in WT plants. In contrast, seedlings of both antisense lines exposed to salt stress had lower shoot Na+/K+ ratios and longer roots than WT seedlings, indicating that A2 and A3 were more salt-tolerant than WT in the seedling stage, likely because growth is less dependent on photosynthesis in the seedling than in the flowering stage. These results suggested CNGC gene might play a different role during different developmental stages and in various plant organs.

碩士
國立清華大學
奈米工程與微系統研究所
96
pH is a familiar noun in our daily life, it represents the concentration of hydrogen ion in a solution, the lower pH value means higher hydrogen ion concentration. pH value is significantly effective in many fields, such as biology, chemistry, agriculture and so on. The measurement of pH value is an important topic. An intrinsic surface electron accumulation layer is existed in indium nitride. The surface electron concentration is sensitive to the variation of environment. In order to bring surface electron in to full play, ultra thin InN film (~10nm) was used in this study. The pH sensor was realized by the form of Ion Sensitive Field Effect Transistor (ISFET). In the range of pH value 2 to 10, there is Nernst response 58.33mv/pH, which is very close to the theoretical value 59.16mv/pH calculated by Nernst equation. When operated in current mode and applied voltage 0.5V, the current variation was 37uA per pH, which is one order higher than the ISFET made by AlGaN/GaN heterostructure. It’s resulted from the property of surface electron accumulation. Many important performance factor of sensor was investigated, such as response time, detection limit, precision, etc. Finally, by the way of negative charged Au nanoparticles detection, it shows the potential to detect other charged particles or molecules.

博士
長庚大學
電子工程研究所
94
For environmental protection, process control in industry, research and human body monitoring, chemical sensors have been widely applied to determine different analytes. To realize multi-ion micro sensor array, the ISFET/REFET structure was chosen due to the advantages of miniaturization viability, easy processing and low costs. For development of new pH-sensitive membranes, the systematic studies on the properties of various inorganic materials used in microelectronic such as: SiGe, HfO2 and Si3N4 were performed. The pH-sensing area of EIS structures was defined by the deposition of chemically resistant encapsulat - photosensitive epoxy resin, SU8 2005. Although SiGe membranes exhibited high sensitivity, 59.8 mV/pH, their stability was very poor. It was found that HfO2 layer directly deposited on Si could be a good alternative to replace the conventional stacked gate structure, which may economize the thermal oxidation process. With PDA treatment at 900°C, pH sensitivity, drift coefficient and hysteresis width for 8 nm thick HfO2 layer was 58.3 mV/pH, 0.65 mV/h and 1.7 mV, respectively. The pH sensitivity of Si3N4-ISFETs without extended source and drain areas, designed and fabricated in CGU was 40 mV/pH. The pH sensitivity and drift coefficient of Si3N4-ISFETs with extended source and drain areas made in ITE was 47.6 mV/pH and -0.68 mV/h, respectively. REFETs were fabricated by the deposition of organic PVC membranes on the top of Si3N4-ISFETs modified with HMDS. The pH sensitivity of REFETs with the optimized PVC membranes based on 60%-DNP was reduced to 10.8 mV/pH at linearity of 99.7% and lifetime - 15 days. The measurements were performed in IBIB PAN. It was stated that the developed inorganic and organic ion-sensitive membranes can be applied in ISFET/REFET structure. Based on the achievements in this study, other ion micro sensors can be also developed for smart sensor array application.

碩士
國立清華大學
電子工程研究所
97
本研究目的在於開發出感測濃度達到fM(10-15 M)等級的多巴胺感測元件，此感測元件由TSMC CMOS 0.35 �慆製程製作而成，我們把從製程廠製作回來的晶片，經由一連串的後製程，首先經由硫酸濕蝕刻掉金屬層，再經由KOH濕蝕刻掉多晶矽，以露出我們所需要的感測區域，而完成了感測元件OGFET(開閘極場效電晶體)。 此篇論文的特點在於將感測元件與感測電路整合在一顆晶片上，而感測電路方面則是4乘4的感測陣列，感測電路原理為將感測元件電流轉換至數位脈波輸出的感測機制，有鑑於以往傳統式ISFET感測電路為電阻式放大器，但輸出的變化量都在mv(毫伏)範圍；而我們所設計的電路正好彌補了此不足，其優點在於能夠將大範圍的電流感測出來並且以數位脈波輸出，而我們所設計的電路感測電流範圍在40 nA ~6 �嫀之間。 在整個晶片完成了硫酸濕蝕刻等後製程後，必須在其感測表面進行分子固定化，用意在於能夠抓取我們想要量測的生物分子(在此為多巴胺)，抓取到的多巴胺分子帶有負電，使得所量測的I-V曲線產生位移而能感測到fM(10-15 M)等級的多巴胺溶液。 我們在此篇論文中利用傳統CMOS製程開發出極靈敏的離子電晶體感測器，而能夠達到與奈米金線場效電晶體相同的感測靈敏度(NWFET)；本研究最重要的地方在於能夠將感測元件與電路整合在一個系統中，這對於低成本開發無疑是一個絕對的幫助，且因晶片面積小而能夠達到隨身攜帶的目的，對於病人的即時偵測非常的有用。

碩士
國立清華大學
電子工程研究所
107
How to detect the disease of a patient is a very important issue in medical treatment. According to statistics, one third of people has been infected with hepatitis B virus, and the region of the highest hepatitis prevalence in the world occurs in Taiwan. If there is a rapid and simple method to detect a lower concentration of hepatitis B viral load in serum, it facilitates early diagnosis of hepatitis B virus infection and prevention of further transmission. Ion-sensitive field-effect transistors are presented in this case to get a real-time detection of a lower concentration DNA molecules (fM level). Ion-sensing field-effect transistors are fabricated using TSMC 0.35μm CMOS process. And then surface functionalization and DNA molecules are modified on the passivation of sensors by Self-assembled monolayers. In terms of circuit design, we design different sizes of ISFETs with interdigitated electrodes or planar electrodes to explore the characteristics of the sensors. The best sensitivity of the designs in this case is 32mV/pH. In the end, this scheme can be combined with the readout circuit for the measurement of several sensors and convert the ISFET current to a digital output signal. Due to DNA molecules have the negatively electrical property, the output frequency will be increased when target DNAs hybridize with probe DNAs.

Thesis (M.S.)--Florida State University, 2008.
Advisor: Lei Zhu, Florida State University, College of Arts and Sciences, Dept. of Chemistry and Biochemistry. Title and description from dissertation home page (viewed Sept. 16, 2008). Document formatted into pages; contains xiii, 60 pages. Includes bibliographical references.

碩士
中原大學
電子工程研究所
85
The Ion Sensitive Field Effect Transistor (ISFET) is a new integrated device composed of a conventional ion selective electrode (ISE) and a Metal-lnsulator-Semiconductor FET (MISFET). The first ISFET was reported by P.Bergveld in 1970. The device is similar to the conventional MISFET except that the metal gate electrode is removed in order to expose the underlying insulator layer to solution. The gate insulator plays the role of an ion selective electrode. ISFET''s have potential advantages over conventional ion selective electrodes in their rapid response, small size, high input impedance and low output impedance, and are extremely attractive for biomedical applications. 　　In this thesis, the silicon nitride (Si3N4) materials have been used as the pH-sensitive surface in the ISFET and this material is IC-process compatible. Based on the measurement of current-voltage (I-V) curves, the pH sensitivity was determined through the shift of the linear region threshold voltage (△VT) of the ISFET sensor. The experimental studies have been confirmed that the pH sensitivity and linearity of Si3N4 surface for the pH-ISFET is perfect to silicon dioxide (SiO2) materials, but also for Si3N4 materials to exhibit a Nernstian pH response by treatment in hydrofluoric acid (HF).

碩士
中原大學
電子工程研究所
86
The ion sensitive field effect transistor (ISFET) is a device composed of a conventional ion selective electrode and a MOSFET device, and applied to the measurement of the ion content in the solution. ISFET*s have potential advantages overconventional ion selective electrodes in their rapid response, small size, and low output impedance. Additionally, the use of IC technology allows low cost fabrication. In this study, the tin-oxide(SnO2) as a new pH sensor layer for ISFET was investigated. It consists of three topics.The first topic is on the characteristics of SnO2 film for ISFET. The characteristics of ISFET including sensitivity (55~59 mV/pH for SnO2), long term drift( about 1~2 mV/hr), hysteresis( about 8 mV), response time (< 0.5 sec) were reported by the experiments. For improving the simulation method of ISFET, we will also calculate the series resistances between drain and source. The second topic is on the characteristics of ISFET. The temperature effect was measured (0℃~70℃). Furthermore the zero temperature coefficient adjustment and the temperature coefficient compensation were discussed.The third topic is on the measurement of pHpzc. The extraction of the point of zero charge(pHpzc) was discussed in this thesis. The value of pHpzc is 5.65 in the flat band condition and 6 in the linear region. It is useful for the simulation of the surface potential.

碩士
國立清華大學
電子工程研究所
98
Ultrathin (~10 nm) InN ion sensitive field effect transistors (ISFETs) modified with 3-aminopropyltrimethoxysilane (APTMS) by molecular vapor deposition (MVD). It is used to selectively detect calcium ions. The ultrathin InN ISFETs have high sensitivity and short response time for anion detection, showing a great potential for chemical and biological sensing applications. The change of water contact angle on InN surface was observed from 74o, indicating the O2 plasma cleaning, to 61o after 1 hour vapor deposition. APTMS with –NH2 terminal functional groups react to the cross-linker, glutaraldehyde, is used to immobilize O-phospho-l-tyrosine (p-Tyr) with phosphate end. After immersed in 1 mM p-Tyr solution for 12 hours, the functionalized InN ISFET is used to complex with calcium ion. A source-drain current increase is observed when calcium ion introduced to the gate region of ISFETs. The current increase is attributed to the binding of positively charged calcium ion. The sensitivity is about 1.11 %/decade, and detection limit is 10-6 M. When InN ISFET is immersed to sodium chloride, potassium chloride, magnesium chloride solution individually, we can calculate that the sensitivity on calcium ion is 6.53, 3.2, 27.9 times than sodium, potassium, and magnesium ions.

碩士
國立成功大學
微電子工程研究所
104
Ion-sensitive field-effect transistors (ISFET) are fabricated using intrinsic hydrogen-terminated high temperature high pressure single crystalline diamond (HPHT-SCD) films. The properties of ion-sensitive field-effect transistors (ISFET) are realized by a surface conductive channel on hydrogen-terminated diamond. The gating is realized by immersing the diamond surface into phosphate buffered s solution which is contacted by a platinum electrode. The surface of hydrogen terminated diamond without any additional oxide layer acts as a gate insulation. The response of gate potential to pH is about −45.18 mV/pH. The results are discussed in terms of transfer doping mechanism, Nernst equation, and electrochemical properties of diamond surfaces. They are also compared with ISFETs which employ ion-sensitive gate oxides.

博士
國立清華大學
電子工程研究所
98
Ion selective field effect transistor (ISFETs) based on single crystal indium nitride (InN) film have been demonstrated for detecting pH values, anions and polarity in liquids. Three kinds of InN ISFETs containing 10-nm-thick, 1-um-thick and 1.2 um, magnesium (Mg) doped InN have been investigated by electrolyte-gate-biased current-voltage (IDS-VGS) measurements. IDS-VGS characteristics reveal that the a-InN:Mg ISFETs have a large (~52%) current variation ratio at a gate bias of 0.3 V with respect to the unbiased one, which is higher than that from the undoped InN ISFETs (~18% and <0.1% for 10-nm and 1-�慆-thick –c-InN epilayers, respectively). The ultrathin InN and a-InN:Mg ISFETs can also function as pH sensor with a high sensitivity (58.25 mV/pH), a high resolution (0.05 pH), and a short response time(<10 s). For anion sensing applications, the positively charged donors on InN surfaces selectively adsorbed anions and built Helmholtz voltages near the InN/solution interface. The InN ISFETs reveal remarkable selectivity, response time, signal stability, and repeatability for chloride ions. Chemical response to polar liquids including methanol, IPA and acetone, etc, shows a linear relationship with the ratio of dipole moment to dielectric constant of the liquid.

碩士
國立清華大學
電子工程研究所
98
Ultrathin (~10 nm) InN ion sensitive field effect transistors (ISFETs) with gate region modified with 3-mercaptopropyltrimethoxysilane (MPTMS) by molecular vapor deposition (MVD) are used to detect hybridization of deoxyribonucleic acid (DNA). The ultrathin InN ISFETs have a high sensitivity and short response time for anion detection, showing a great potential for chemical and biological sensing applications. Vapor-phase silanization of MPTMS using MVD substantially shortens the response time for surface modification compared to the conventional self-assembled monolayer (SAM) techniques. The change of contact angle of water on InN surface was observed from 0o, indicating the O2 plasma cleaning, to 68o after 1.5 h vapor deposition. MPTMS with -SH terminal functional groups was used to immobilize probe DNA with acrylic phosphoramidite modification at 5'-end. After immersed in 10 uM DNA probes solution for 12 h, the functionalized InN ISFET was used to perform the hybridization with complementary single stranded (ss) DNA 5'-ATTGTTATTAGG-3'. A drain-source current decrease (~6 uA) was observed when a complementary DNA was introduced to the gate region of ISFETs. The current decrease is attributed to the attachment of negatively charged DNA. For a 12-mer oligonucleotide probe, the detection of 1 nM target DNA was accomplished, while the noncomplementary DNA with one base mismatch did not show any obvious current variation.