No description available.

The Large Hadron Collider (LHC) at the CERN laboratory was designed to study the elementary particles and forces and search for new physics.  Detectors at LHC were designed to observe proton-proton collisions with center of mass energies up to 14 TeV, seven times higher than previously possible. One of the largest of these is the general purpose detector ATLAS. After almost 20 years of planning and construction, LHC and its detectors were finished in 2008. Since then ATLAS has produced valuable data, which contributed to the discovery of the 1964 postulated Higgs-particle and thus to the Nobel prize in physics in 2013. To expand the searches, LHC and its detectors will undergo several upgrades to the increase luminosity at least by a factor of 5 and to exploit the full potential of the machine. In order to adapt the detector to the resulting increasing event rates and radiation levels, new electronics have to be developed. This thesis describes the development process of a new upgraded digital readout system for one of the sub-detectors in ATLAS, the scintillating Tile Calorimeter (TileCal), and more specifically one of its key components, the high-speed data link DaughterBoard. Starting from the idea of transferring all recorded information of the detector using high speed serial optical links and the concept of using re-programmable logic for the readout electronics, completely new on-detector electronics were designed to be used as a core component for communication, control and monitoring. The electronics was tested, electrical characterized and proven to work in a setup similar to the upgraded readout electronics. The DaughterBoard is the Stockholm University contribution to the ATLAS upgrade in 2023.

Σε αυτήν την εργασία περιγράφεται αναλυτικά ένα κύκλωμα ανάγνωσης για ηλεκτροχημικό βιοαισθητήρα, καθώς και η κατάλληλη τροποποίησή του ώστε να μπορεί να χρησιμοποιηθεί σε σύστημα χωρητικού βιοαισθητήρα. Βασικός στόχος και στις δύο περιπτώσεις είναι η συμβατότητα των κυκλωμάτων με πλήρως ολοκληρωμένα βιοχημικά μικροσυστήματα, με έμφαση στη μικρή επιφάνεια ολοκλήρωσης και τη χαμηλή κατανάλωση. Κεντρικό στοιχείο των δύο υλοποιήσεων αποτελεί ο χωρητικός ενισχυτής διαντίστασης ο οποίος αναλαμβάνει το ρόλο της μετατροπής της χρήσιμης πληροφορίας, που είναι ένα ρεύμα, σε μία τάση. Αυτή η τάση στη συνέχεια μπορεί να δοθεί για ψηφιακή επεξεργασία, αφού περάσει από έναν ADC . Τα δύο κυκλώματα σχεδιάσθηκαν σε τεχνολογία CMOS της TSMC των 90nm και εμφάνισαν στις εξομοιώσεις ικανοποιητικά χαμηλό θόρυβο. Το κύκλωμα του ηλεκτροχημικού βιοαισθητήρα παρουσίασε καλή γραμμικότητα για ρεύματα από 10nA έως 10uA, ενώ το αντίστοιχο του χωρητικού βιοαισθητήρα είναι δυνατό να μετρήσει χωρητικότητες με μέγιστη απόκλιση 3%. / This paper presents a readout circuit for electrochemical biosensors and the appropriate modification of the circuit to make it compatible with capacitive biosensors. The main goal is to ensure compatibility of the circuits with fully integrated biochemical microsystems and therefore emphasis is placed on achieving small area and low consumption. The fundamental part of the circuits is a Capacitive Transimpedance Amplifier that is responsible for converting the current signal to a voltage. That voltage can then be passed forward to digital processing with the use of an ADC. Both circuits were designed using 90nm TSMC CMOS technology and showed low noise in simulations. The electrochemical biosensor readout circuit achieves good linearity in a range of 10nA to 10uA, while the capacitive biosensor readout circuit is capable of measuring capacitances with a 3% error.

ALICE (A Large Ion Collider Experiment) is the heavy-ion experiment at the Large Hadron Collider (LHC) at CERN. As an important part of its upgrade plans, the ALICE experiment will schedule the installation of a new Inner Tracking System (ITS) during the Long Shutdown 2 (LS2) of the LHC. The new ITS layout will consist of seven concentric layers, ¿ 12.5 Gigapixel camera covering about 10m2 with Monolithic Active Pixel Sensors (MAPS). This choice of technology has been guided by the tight requirements on the material budget of 0.3% X/X0 per layer for the three innermost layers and backed by the significant progress in the field of MAPS in recent years. The technology initially chosen for the ITS upgrade is the TowerJazz 180 nm CMOS Technology. It offers a standard epitaxial layer of 15 - 18 µm with a resistivity between 1 and 5 k¿ cm¿1 and a gate oxide thickness below 4 nm, thus being more robust to Total Ionizing Dose (TID). The main subject of this thesis is to implement a novel digital pixel readout architecture for MAPS. This thesis aims to study this novel readout architecture as an alternative to the rolling-shutter readout. However, this must be investigated through the study of several chip readout architectures during the R&D phase. Another objective of this thesis is the study and characterization of TowerJazz, if it meets the Non-Ionizing Energy Loss (NIEL) and Single Event Effects (SEE) of the ALICE ITS upgrade program. Other goals of this thesis are: ¿ Implementation of the top-down flow for this CMOS process and the design of multiple readouts for different prototypes up to the assembly of a full-scale prototype. xvii Abstract ¿ Characterization of the radiation hardness and SEE of the chips submitted to fabrication. ¿ Characterization of full custom designs using analog simulations and the generation of digital models for the simulation chain needed for the verification process. ¿ Implementation and study of different digital readouts to meet the ITS upgrade program in integration time, pixel size and power consumption, from the conceptual idea, production and fabrication phase. Chapter 1 is a brief overview of CERN, the LHC and the detectors complex. The ALICE ITS will be explained, focusing on the ITS upgrade in terms of detector needs and design constraints. Chapter 2 explains the properties of silicon detectors and the detector material and the principles of operation for MAPS. Chapters 3 and 4 describe the ALPIDE prototypes and their readout based on MAPS; this forms the central part of this work, including the multiple families of pixel detectors fabricated in order to reach the final design for the ITS. The ALPIDE3/pALPIDE3B chip, the latest MAPS chip designed, will be explained in detail, as well focusing in the matrix digital readout. In chapter 5 the noise measurements and its characterization are presented including a brief summary of detector response to irradiation with soft X-rays, sources and particle beams. / El sub detector ITS (Inner Tracking System) del detector ALICE (A Large Ion Collider Experiment) es un detector de vértice y es el detector mas cercano al punto de interacción. Se encuentra conformado por 3 tipos de subdetectores, dos capas de pixel de silicio (Silicon Pixel Detectors), 2 capas de acumulación de silicio (Silicon Drift Detectors) y 2 capas de banda de Silicio (Silicon Strip Detectors). La función primaria del ITS es identificar y rastrear las partículas de bajo momentum transversal. El detector ITS en sus dos capas más internas están equipadas con sensores de silicio basados en píxeles híbridos. Para reemplazar esta tecnología de Píxeles, el detector ITS actual será reemplazado por un nuevo detector de una sola tecnología, ampliando su resolución espacial y mejorando el rastreo de trazas. Este nuevo detector constará de siete capas de sensores de píxeles activos monolíticos (MAPS), las cuales deberán satisfacer los requerimientos de presupuesto de materiales y ser tolerantes a mayores niveles de radiación para los nuevos escenarios de incrementos de luminosidad y mayores tasas de colisiones. Los sensores MAPS que integran el sensor de imagen y los circuitos de lectura se encuentran en la misma oblea de silicio, tienen grandes ventajas en una buena resolución de posición y un bajo presupuesto material en términos de bajo coste de producción. TowerJazz ofrece la posibilidad de una cuádruple-WELL aislando los transistores pMOS que se encuentran en la misma nWELL evitando la competencia con el electrodo de recolección, permitiendo circuitos mas complejos y compactos para ser implementados dentro de la zona activa y además posee una capa epitaxial de alta resistividad. Esta tecnología proporciona una puerta de óxido muy delgado limitando el daño superficial por la radiación haciéndolo adecuado para su uso denxiii Resúmen tro del experimento ALICE. En los últimos cuatro años se ha llevado a cabo una intensiva I+D en MAPS en el marco de la actualización del ITS de ALICE. Varios prototipos a pequeña escala se han desarrollado y probado exitosamente con rayos X, fuentes radioactivas y haces de partículas. La tolerancia a la radiación de ALICE ITS es moderada con una tolerancia de irradiación TID de 700 krad y NIEL de 1 × 1013 1 MeV neqcm¿2 , MAPS es una opción viable para la actualización del ITS. La contribución original de esta tesis es la implementación de una nueva arquitectura digital de lectura de píxeles para MAPS. Esta tesis presenta un codificador asíncrono de direcciones (arquitectura basada en la supresión de ceros transmitiendo la dirección de los píxeles excitados denominada PADRE) para la arquitectura ALPIDE, el autor también hizo una contribución significativa en el ensamblaje y veri- ficación de circuitos. PADRE es la principal investigación del autor, basada en un codificador de prioridad jerárquica de cuatro entradas y es una alternativa a la arquitectura de lectura rolling-shutter. Además de los prototipos a pequeña escala, también se han desarrollado prototipos a escala completa a las necesidades del detector ITS (15 mm y 30 mm) empleando un nuevo circuito de lectura basado en la versión personalizada del circuito PADRE. El pALPIDEfs fue el primer prototipo a escala completa y se caracterizó obteniendo un tiempo de lectura de la matriz por debajo de 4 µs y un consumo de energía en el orden de 80 mWcm¿2 . En general, los resultados obtenidos representan un avance significativo de la tecnología MAPS en cuanto al consumo de energía, velocidad de lectura, tiempo de recolección de carga y tolerancia a la radiación. El sensor pALPIDE2 ha demostrado ser una opción muy atractiva para el nuevo detector ITS, satisfaciendo los requerimientos en términos de eficiencia de detección, fake-hit rate y resolución de posición, ya que su rendimiento no puede alcanzarse mediante prototipos basados en la arquitectura de lectura tradicionales como es / El subdetector ITS (Inner Tracking System) del detector ALICE (A Large Ion Collider Experiment) és un detector de vèrtex i és el detector mes proper al punt d'interacció. Es troba conformat per 3 tipus de subdetectors, dues capes de píxel de silici (Silicon Pixel Detectors), 2 capes d'acumulació de silici (Silicon Drift Detectors) i 2 capes de banda de Silici (Silicon Strip Detectors). La funció primària del ITS és identificar i rastrejar les partícules de baix moment transversal. El detector ITS en les seues dues capes més internes estan equipades amb sensors de silici basats en píxels híbrids. Per a reemplaçar aquesta tecnologia de Píxels, el detector ITS actual serà reemplaçat per un nou detector d'una sola tecnologia, ampliant la seua resolució espacial i millorant el rastreig de traces. Aquest nou detector constarà de set capes de sensors de píxels actius monolítics (MAPS), les quals hauran de satisfer els requeriments de pressupost de materials i ser tolerants a majors nivells de radiació per als nous escenaris d'increments de lluminositat i majors taxes de col·lisions. Els sensors MAPS que integren el sensor d'imatge i els circuits de lectura es troben en la mateixa hòstia de silici, tenen grans avantatges en una bona resolució de posició i un baix pressupost material en termes de baix cost de producció. TowerJazz ofereix la possibilitat d'una quàdruple-WELL aïllant els transistors pMOS que es troben en la mateixa nWELL evitant la competència amb l'elèctrode de recol·lecció, permetent circuits mes complexos i compactes per a ser implementats dins de la zona activa i a més posseeix una capa epitaxial d'alta resistivitat. Aquesta tecnologia proporciona una porta d'òxid molt prim limitant el dany superficial per la radiació fent-ho adequat per al seu ús dins de l'- experiment ALICE. En els últims quatre anys s'ha dut a terme una intensiva R+D en MAPS en el marc de l'actualització del ITS d'ALICE. Diversos prototips a petita escala s'han desenvolupat i provat ix Resum reeixidament amb rajos X, fonts radioactives i feixos de partícules. La tolerància a la radiació d'ALICE ITS és moderada amb una tolerància d'irradiació TID de 700 krad i NIEL d'1× 1013 1MeV neqcm¿2 , MAPS és una opció viable per a l'actualització del ITS. La contribució original d'aquesta tesi és la implementació d'una nova arquitectura digital de lectura de píxels per a MAPS. Aquesta tesi presenta un codificador asíncron d'adreces (arquitectura basada en la supressió de zeros transmetent l'adreça dels píxels excitats denominada PADRE) per a l'arquitectura ALPIDE, l'autor també va fer una contribució significativa en l'assemblatge i verificació de circuits. PADRE és la principal recerca de l'autor, basada en un codificador de prioritat jeràrquica de quatre entrades i és una alternativa a l'arquitectura de lectura rolling-shutter. A més dels prototips a petita escala, també s'han desenvolupat prototips a escala completa a les necessitats del detector ITS (15 mm i 30 mm) emprant un nou circuit de lectura basat en la versió personalitzada del circuit PADRE. El pALPIDEfs va ser el primer prototip a escala completa i es va caracteritzar obtenint un temps de lectura de la matriu per sota de 4 µs i un consum d'energia en l'ordre de 80 mWcm¿2 . En general, els resultats obtinguts representen un avanç significatiu de la tecnologia MAPS quant al consum d'energia, velocitat de lectura, temps de recol·lecció de càrrega i tolerància a la radiació. El sensor pALPIDE2 ha demostrat ser una opció molt atractiva per al nou detector ITS, satisfent els requeriments en termes d'eficiència de detecció, fake-hit rate i resolució de posició, ja que el seu rendiment no pot aconseguir-se mitjançant prototips basats en l'arquitectura de lectura tradicionals com és el rolling-shutter dissenyat en la mateixa tecnologia. Per aquesta raó, la R+D en els prototips ALPIDE ha continuat amb l'objectiu d'optimitza / Marín Tobón, CA. (2017). PADRE pixel read-out architecture for Monolithic Active Pixel Sensor for the new ALICE Inner Tracking System in TowerJazz 180 nm technolog [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/86154 / TESIS

This thesis introduces an innovative approach for enhancing the characterization of radiation field quality through microdosimetry. Over the past 30 years, clinical results have shown that ion therapy may be a superior treatment option for several types of cancer, including recurrent cancers, compared to conventional radiation. Despite these promising results, there are still several treatment uncertainties related to biological and physical processes that prevent the full exploitation of particle therapy. Among the physical characterizations, it is paramount to measure the quality of the irradiating field in order to link the biological effect to its physical description. In this way, uncertainties in treatment can be reduced and outcomes optimized. One tool for studying the radiation field that has become increasingly important in the last decade is microdosimetry . Over the last years, microdosimetry has proved to be a superior tool for describing radiation quality, especially when compared to standard reference quantities used nowadays in the clinic. In microdosimetry, the fundamental quantity is the lineal energy y, defined as the energy deposition in the detector divided by the Mean Chord Length (MCL): an approximation used to estimate the track length traveled by radiation in the detector, valid in an isotropic, uniform radiation field. As a consequence, microdosimeters has evolved in obtaining the best possible energy release estimation, without improving the accuracy of the MCL approximation. Measuring the Real Track Length (RTL) traveled by the particle inside the detector could provide a better description of the radiation quality. In fact, from a biological perspective, it is critical if a large amount of energy is released over a long particle track, or if it is extremely dense over a small particle track. If the energy released is more dense, the biological damage induced is likely to be more complex and therefore more significant. For these reasons, a novel approach to microdosimetry is presented that considers the RTL in the radiation quality description. The first chapter of the thesis presents standard microdosimetry and its main quantities. A special emphasis is given to the microdosimeter used in this work, i.e. the TEPC or Tissue Equivalent Proportional Counter, a gas microdosimeter that is equivalent in terms of energy deposition to 2 um of tissue. A comprehensive characterization of the TEPC response to different ions and energies can be found in the literature. A topic missing in the literature is the investigation of the TEPC response to clinical protons of different particles rates. A section is dedicated to the TEPC detector response to pileup. Pileup occurs where two or more energy deposition events are processed together, disrupting the normal signal processing. By exposing the TEPC to particles rates ranging from few particles per seconds to 106 particles per second, it was possible to estimate the distortion of the acquired spectra due to pileup. On the other hand, by using Monte Carlo simulations, it was possible to reproduce the effect of pileup on microdosimetric spectra. Using a quantitative approach, the experimental spectra measured at different particles rate and the spectra simulated at a different pileup probability are matched based on a similarity criteria. In this way, it was possible to build a particle rate-pileup curve for the TEPC, used to quantify the pileup probability contribution. More in general, this approach could be extended and used to other microdosimeters. The acquisition of the data in pileup condition is sometimes inevitable, and some microdosimeters are more likely to suffer from high particle rates. With this part of the thesis, I aim to provide a tool to acquire microdosimetric spectra even in pileup condition. A description of the TEPC acquisition chain is provided in the next section. This is an important topic as any further integration or improvement will require the modification of at least one element of the acquisition. Then, the typical data analysis carried out on the microdosimetric spectra is presented, together with the calibration procedure of the TEPC detector based on Monte Carlo simulation using Geant4. Finally, I provide an overview of the software Mandarina, which is the implemented Graphical User Interface (GUI), written in C# language, and developed specifically to analyze the experimental microdosimetric data. By using this software, users can build a microdosimetric spectra starting from raw acquired data. In addition, the software provides the ability to modify key acquisition parameters and provides real-time feedback on how the microdosimetric spectra change under these modifications. Then, I introduce the concept of Hybrid Detector of Microdosimetry (HDM). HDM is composed of a commercial TEPC, and 4 layers of Low Gain Avalanche Detectors (LGADs). LGADs are silicon detectors featuring an internal gain by exploring the avalanche effect. This makes them suitable to detect particles with a broad range of energy release in the silicon. A detailed description of how the LGADs detect ionizing radiation is provided in this work. LGADs are used in the HDM as a tracking component, capable of reconstructing the particle trajectories inside the TEPC. In this way, instead of relying on the MCL approximation to calculate the value of y, it is possible to define a new quantity: yr. yr differs from the standard y because it uses the real track length instead of the mean chord length approximation. Next, a preliminary Geant4-based study for optimizing the detector geometry is discussed. Tracking capability and simulated microdosimetric spectra with the estimated track length were assessed and are presented in this thesis. To experimentally realize HDM, the acquisition chain of the TEPC must be upgraded since the original acquisition system cannot directly integrate the tracking information from the LGADs strips. A chapter of this work is dedicated to the implementation of the new acquisition system, which allows for the digitalization of the time series signal produced by the detector. The system is based on an Eclypse-Z7 FPGA development board which can host up to 4 Analog to Digital Converters (ADC). Following a bottom-up approach, this chapter describes first the main characteristics of the signal to be digitized. An overview of the Eclypse-Z7 development board with its main capabilities is provided. Finally, the controller in charge of driving the ADC is described. Being a Zynq FPGA, both Programming Logic (PL) and Processing System (PS) need to be programmed. The PL is responsible for driving the ADC at a low level, controlling the triggering and the data flow to the PS. The PS hosts a custom Linux distribution with the task of supervising the acquisition by setting the main parameters, like the number of samples to acquire, the trigger condition and position with respect to the acquisition window. The PS is also responsible for storing the data safely into an SD card connected to the Eclypse-Z7. With a fully customizable system, it is then possible to integrate other systems by properly synchronizing the acquisition with other devices. In the specific case of HDM, a correspondence between the energy release and the LGAD-based tracking component needs to be implemented. Once the time series is properly acquired, the data analysis needs to be developed. A specific section of the thesis is dedicated to this important task, as the correct processing of the signals is a requirement to obtain robust microdosimetric spectra. The time series processing features a classification algorithm that allows to identify artifacts of the acquired signals, such as saturation, double hits and noisy signals. Once the time series are correctly processed and the relevant information is extracted, it is possible to calculate the microdosimetric spectra. In this acquisition chain the detector signal is processed with 3 different levels of gain, obtaining the same version of the signal but with different amplification. In this way it is possible to span a large dynamic range while maintaining the required resolution typical of microdosimetry. However, the three signals must be then joined together to span the required dynamic range. This process goes under the name of intercalibration and has a dedicated section in the chapter. Once the signals are intercalibrated, it is necessary to apply a calibration. The new calibration process developed within this work differs from the previously adopted calibration method based on Monte Carlo simulation, and is described in detail. Finally, the spectra obtained with the new acquisition are compared to those obtained with the original acquisition chain. The next chapter is dedicated to the LGAD readout. Again, following a bottom up approach, an introduction to the LGAD signal is provided. This readout acquisition chain is already partially available since it has been developed by the INFN-TO (Istituto Nazionale di Fisica Nucleare) of Turin. For the first stage of signal processing, two main components developed by the aforementioned INFN-TO are available: the ABACUS chip and the ESA_ABACUS printed circuit board (PCB) board. The ABACUS chip is an ASIC (application-specific integrated circuit) designed to process directly the small signal coming from the LGADs strips. At each activation of one LGAD strip, a digital signal is generated. Each ABACUS is capable of handling up to 24 LGADs strips and can adjust the threshold of each channel within a limited range. Threshold adjustment is required to separate the signal from the noise, as it is expected that all the channels do not share a common threshold due to their specific noise. The ABACUS PCB has been developed to physically host up to 6 ABACUS chips plus the LGAD sensor. It is equipped with an internal DAC (Digital to Analog Converted) used to set a common threshold for all 24 channels managed by one ABACUS chip. In this way, a common threshold can be selected using the ABACUS DAC, and then, to satisfy the specific needs of each channel, the ABACUS chip is used. In order to program the thresholds, the manufacturer required specific serial communication protocols. It is necessary to integrate this communication protocol into the acquisition system. To meet these requirements, I developed an FPGA-based readout system capable of processing the signal from the ABACUS chip and setting the threshold for each channel. I describe in detail the implementation of such a system in a dedicated chapter, again following a bottom-up approach starting from the PL, and moving to the PS. In a specific section, I show how the communication protocol has been implemented and tested and how the fast digital pulses, coming from the ABACUS chip, are processed in the PL. I also describe how the PS system was built. As in the case of the new TEPC acquisition, a Linux system was run on the PS. This made it easier for the end user to work with the acquired data and threshold controls. The movement of data from the PL to the PS is accomplished using DMA or Direct Memory Access. This is a critical component because it allows fast (within one clock cycle) data transfer from the PL to the user in the PS. The implementation of such architecture is quite complex and demands both knowledge in advanced electronics and Linux systems. In fact, the DMA requires the implementation of a Linux kernel driver to correctly move the data. This process is described in a dedicated section of this thesis. With this implementation design in the FPGA it was possible to acquire the signal from 24 LGADs strips and control the thresholds. An experimental campaign was conducted at the proton therapy center in Trento where the whole acquisition system was tested extensively. The results are reported in a dedicated section of this thesis. All the signals coming from the protons with energies ranging from 70 to 228 MeV were correctly discriminated, proving that the readout system can work with protons of clinical energies. Finally, thermal tests were conducted on the acquisition setups since during the experimental campaign some thermal drifts of the baseline were observed. The test results are shown in a dedicated section of this thesis. Finally, I included a chapter on discussion on the results achieved and on future perspective.

A discrete, compact, low-power sensor readout circuit that can simultaneously handle two current measurements, and one voltage measurement. This work provides a compact, low-power sensor architecture, with the intent for the serial readout to be replaced with a low-power radio frequency transmitter for continuous monitoring. The proposed circuit is highly precise with an average current draw of 21 micro amps for a sampling frequency of once per minute. The target application is livestock health monitoring, which would be done by placing the sensor and circuit inside of a cow's rumen to monitor changes in pH, lactate, and VFA levels to catch metabolic disease early. / Master of Science / A circuit for reading a sensor with a long battery life. It is small so that it can fit in a cow's stomach to determine if it has a disease in its stomach. This diagnosis can be used to adjust its diet.

This thesis reports the development of high performance readout electronics for resistive microbolometer detector arrays that are used for uncooled infrared imaging. Three different readout chips are designed and fabricated by using a standard 0.6 &micro / m CMOS process. Fabricated chips include a conventional capacitive transimpedance amplifier (CTIA) type readout circuit, a novel readout circuit with dynamic resistance nonuniformity compensation capability, and a new improved version of the CTIA circuit. The fabricated CTIA type readout circuit uses two digital-to-analog converters (DACs) with multiple analog buses which compensate the resistance nonuniformity by adjusting the bias currents of detector and reference resistors. Compensated detector current is integrated by a switched capacitor integrator with offset cancellation capability followed by a sample-and-hold circuit. The measured detector referred current noise is 47.2 pA in an electrical bandwidth of 2.6 KHz, corresponding to an expected SNR of 530. The dynamic nonuniformity compensation circuit uses a feedback structure that dynamically changes the bias currents of the reference and detector resistors. A special feature of the circuit is that it provides continuous compensation for the detector and reference resistances due to temperature changes over time. Test results of the fabricated circuit show that the circuit reduces the offset current due to resistance nonuniformity 42.5 times. However, the calculated detector referred current noise is 360 pA, which limits the circuit SNR to 70. The improved CTIA type readout circuit introduces a new detector biasing method by using an additional auxiliary biasing transistor for better current controllability. The improved readout circuit alleviates the need for high resolution compensation DACs, which drastically decreases the circuit area. The circuit occupies an area of one seventh of the first design. According to test results, the current compensation ratio is 170, and the detector referred current noise is 48.6 pA in a 2.6 KHz bandwidth.

The P22 c2 repressor protein (P22R) binds to DNA sequence-specifically and helps direct the temperate lambdoid bacteriophage P22 to the lysogenic developmental pathway. To gain insight into its DNA binding mechanism, we solved the 1.6 Å x-ray structure of the N-terminal domain (NTD) of P22R in a complex with a DNA fragment containing the synthetic operator sequence [d(ATTTAAGATATCTTAAAT)]2 This operator has an A-T at position 9L and T-A at position 9R and is termed DNA9T. Van der Waals interactions between protein and DNA appear to confer sequence-specificity. The structure of the P22R NTD – NA9T complex suggests that sequence-specificity arises substantially from interaction of a valine with a complementary binding cleft on the major groove surface of DNA9T. The cleft is formed by four methyl groups on sequential base pairs of 5' TTAA 3'. The valine cleft is intrinsic to the DNA sequence and does not arise from protein-induced DNA conformational change. Protein-DNA hydrogen bonding plays a secondary role in specificity.

Detecting elementary particles and observing accompanying events in particle colliders is one of the most important field of current research in experimental physics. TimePix and its successor TimePix3 are types of the currently used detectors which are placed beside other in ATLAS experiment conducted by Eu- ropean Organization for Nuclear Research. Such detectors can produce huge amount of data about passing particles at high rate. The goal of the thesis is to develop methods for detecting and classification of elementary particles observed by detector network ATLAS-TPX3. Suitable methods for clustering and/or classification based on semi-labelled data should be identified or new one should be developed. The proposed methods will be implemented and their performance on real data will be evaluated. The results will also include an implementation of framework for preprocessing low level data from detector network ATLAS-TPX3 in real-time and creating outputs that are suitable for subsequent physics investigation (e.g. ROOT framework files) includ- ing the proposed or future methods for particle classification. 5

This thesis consists of two topics. A frequency-shift readout circuit is integrated for the rapid IgE measurement biomedical system in the first half. Secondly, we present a ROM-less DDFS (direct digital frequency synthesis) using a non-equal division parabolic polynomial interpolation method, which is used as the frequency generator in the measurement system. The first topic investigates the IgE concentration measurement system and realizes the readout circuit using TSMC 1P6M 0.18 £gm CMOS technology. We integrate the flexural plate wave (FPW) sensor chips and an ASIC comprising control block, digital to analog convertor (DAC), OTA-C oscillators, amplifiers, peak detectors, registers, and a subtractor. By taking advantages of the characteristics that the central frequencies of the loaded FPW sensors will be shifted, sine waves with various frequencies are generated and swept through one pair of FPW sensors. The frequency difference of these sensors is then readout to get concentration by look-up table. The second topic investigates the division method of a quarter sine wave to improve the spurious free dynamic range (SFDR) and realizes a ROM-less DDFS which is used as the frequency generator in the mentioned IgE measurement system. The proposed non-equal division parabolic polynomial interpolation method will generate a complete sine wave by a quarter of a sine digital signal owing to the symmetry. We combine the quasi-linear interpolation and an offset adjustment to derive the quarter sine wave digital signals. The proposed method not only reduces the absolute error between ideal sine wave and generated sine wave, it also improves SFDR.