A review of advances in pixel detectors for experiments with high rate and radiation

The Large Hadron Collider (LHC) experiments ATLAS and CMS have established hybrid pixel detectors as the instrument of choice for particle tracking and vertexing in high rate and radiation environments, as they operate close to the LHC interaction points. With the High Luminosity-LHC upgrade now in sight, for which the tracking detectors will be completely replaced, new generations of pixel detectors are being devised. They have to address enormous challenges in terms of data throughput and radiation levels, ionizing and non-ionizing, that harm the sensing and readout parts of pixel detectors alike. Advances in microelectronics and microprocessing technologies now enable large scale detector designs with unprecedented performance in measurement precision (space and time), radiation hard sensors and readout chips, hybridization techniques, lightweight supports, and fully monolithic approaches to meet these challenges. This paper reviews the world-wide effort on these developments.Comment: 84 pages with 46 figures. Review article.For submission to Rep. Prog. Phy

LTCC packaging for Lab-on-a-chip application

LTCC -pakkaus Lab-on-a-chip -sovellukseen. Tiivistelmä. Tässä työssä suunniteltiin, valmistettiin ja testattiin uusi pakkaustekniikka ”Lab-on-a-chip” (LOC) -sovellukseen. Pakkaus tehtiin pii-mikrosirulle, jolla voidaan mitata solujen kiinnittymistä sirun pintaan solujen elinkelpoisuuden indikaattorina. Luotettavuustestaukset tehtiin daisy-chain -resistanssimittauksilla solunkasvatusolosuhteissa. Lisäksi työssä selvitettiin LTCC- ja ”Lab-on-a-chip” -teknologioiden perusteet teoreettiselta pohjalta. Mikrosirun pakkauksessa käytettiin joustavaa LTCC-teknologiaa. Sähköisiin kontakteihin ja niiden suojauksiin käytettiin sekä johtavia että eristäviä epoksi-liimoja. LOC-sovelluksiin on tärkeää kehittää uusia pakkausmenetelmiä jotta näiden laitteiden kaikki ominaisuudet saadaan toimimaan luotettavasti. Pakkaus testattiin samoissa olosuhteissa missä sitä tullaan käyttämään ja pakkaus kesti kaikki nämä haasteet. Lisäksi esitetty valmistusprosessi on sellainen, että sitä voidaan käyttää myös muihin ”Lab-on-a-chip” -sovelluksiin.Abstract. This work presents design, manufacturing and testing of new packaging method for Lab-on-a-chip (LOC) application. Packaging was made for silicon microchip which can measure cell adhesion on chips surface as indication of cell viability. Reliability testing was done with daisy-chain resistance measurement in real conditions. Moreover basic theory of LTCC and Lab-on-a-chip technology is presented. Resilient LTCC technology was used for packaging material and conductive/insulating epoxies were applied for electrical contacts and barriers against the environment. It is fundamentally important to develop new packaging methods for LOC applications, so all the properties can be utilized reliably. Packaging was tested under the cell growth conditions and the package showed to withstand all these challenges. Moreover the presented packaging method is possible to use also in other Lab-on-a-chip applications

Extracellular electrical signals in a neuron-surface junction: model of heterogeneous membrane conductivity

Signals recorded from neurons with extracellular planar sensors have a wide range of waveforms and amplitudes. This variety is a result of different physical conditions affecting the ion currents through a cellular membrane. The transmembrane currents are often considered by macroscopic membrane models as essentially a homogeneous process. However, this assumption is doubtful, since ions move through ion channels, which are scattered within the membrane. Accounting for this fact, the present work proposes a theoretical model of heterogeneous membrane conductivity. The model is based on the hypothesis that both potential and charge are distributed inhomogeneously on the membrane surface, concentrated near channel pores, as the direct consequence of the inhomogeneous transmembrane current. A system of continuity equations having non-stationary and quasi-stationary forms expresses this fact mathematically. The present work performs mathematical analysis of the proposed equations, following by the synthesis of the equivalent electric element of a heterogeneous membrane current. This element is further used to construct a model of the cell-surface electric junction in a form of the equivalent electrical circuit. After that a study of how the heterogeneous membrane conductivity affects parameters of the extracellular electrical signal is performed. As the result it was found that variation of the passive characteristics of the cell-surface junction, conductivity of the cleft and the cleft height, could lead to different shapes of the extracellular signals

Integrated CMOS Capacitance Sensor And Microactuator Control Circuits For On-Chip Cell Monitoring

"Cell Clinics," CMOS/MEMS hybrid microsystems for on-chip investigation of biological cells, are currently being engineered for a broad spectrum of applications including olfactory sensing, pathogen detection, cytotoxicity screening and biocompatibility characterization. In support of this effort, this research makes two primary contributions towards designing the cell-based lab-on-a-chip systems. Firstly it develops CMOS capacitance sensors for characterizing cell-related properties including cell-surface attachment, cell health and growth. Assessing these properties is crucial to all kinds of cell applications. The CMOS sensors measure substrate coupling capacitances of anchorage-dependent cells cultured on-chip in a standard in vitro environment. The biophysical phenomenon underlying the capacitive behavior of cells is the counterionic polarization around the insulating cell bodies when exposed to weak, low frequency electric fields. The measured capacitance depends on a variety of factors related to the cell, its growth environment and the supporting substrate. These include membrane integrity, morphology, adhesion strength and substrate proximity. The demonstrated integrated cell sensing technique is non-invasive, easy-to-use and offers the unique advantage of automated real time cell monitoring without the need for disruptive external forces or biochemical labeling. On top of the silicon-based cell sensing platform, the cell clinics microsystem comprises MEMS structures forming an array of lidded microvials for confining single cells or small cell groups within controllable microenvironments in close proximity to the sensor sites. The opening and closing of the microvial lids are controlled by actuator hinges employing an electroactive polymer material that can electrochemically actuate. In macro-scale setups such electrochemical actuation reactions are controlled by an electronic instrument called potentiostat. In order to enable system miniaturization and enhance portability of cell clinics, this research makes its second contribution by implementing and demonstrating a CMOS potentiostat module for in situ control of the MEMS actuators

CMOS On-Chip 3D Inductor Design & Application in RF Bio-Sensing

abstract: Three-dimensional (3D) inductors with square, hexagonal and octagonal geometries have been designed and simulated in ANSYS HFSS. The inductors have been designed on Silicon substrate with through-hole via with different width, spacing and thickness. Spice modeling has been done in Agilent ADS and comparison has been made with results of custom excel based calculator and HFSS simulation results. Single ended quality factor was measured as 12.97 and differential ended quality factor was measured as 15.96 at a maximum operational frequency of 3.65GHz. The single ended and differential inductance was measured as 2.98nH and 2.88nH respectively at this frequency. Based on results a symmetric octagonal inductor design has been recommended to be used for application in RF biosensing. A system design has been proposed based on use of this inductor and principle of inductive sensing using magnetic labeling.Dissertation/ThesisM.S. Electrical Engineering 201

Lab-on-CMOS Sensors and Real-time Imaging for Biological Cell Monitoring

Monitoring biological cell growth and viability is essential for in vivo biomedical diagnosis and therapy, and in vitro studies of pharmaceutical efficacy and material toxicity. Conventional monitoring techniques involve the use of dyes and markers that can potentially introduce side effects into the cell culture and often function as end-point assays. This eliminates the opportunity to track fast changes and to determine temporal correlation between measurements. Particularly in drug screening applications, high-temporal resolution cell viability data could inform decisions on drug application protocols that could lead to better treatment outcomes. This work presents development of a lab-on-chip (LoC) sensor for real-time monitoring of biological cell viability and proliferation, to provide a comprehensive picture of the changes cells undergo during their lifecycle. The LoC sensor consists of a complementary metal-oxide-semiconductor (CMOS) chip that measures the cell-to-substrate coupling of adherent cells that are cultured directly on top. This technique is non-invasive, does not require biochemical labeling, and allows for automated and unsupervised cell monitoring. The CMOS capacitance sensor was designed to addresses the ubiquitous challenges of sensitivity, noise coupling, and dynamic range that affect existing sensors. The design includes on-chip digitization, serial data output, and programmable control logic in order to facilitate packaging requirements for biological experiments. Only a microcontroller is required for readout, making it suitable for applications outside the traditional laboratory setting. An imaging platform was developed to provide time-lapse images of the sensor surface, which allowed for concurrent visual and capacitance observation of the cells. Results showed the ability of the LoC sensor to detect single cell binding events and changes in cell morphology. The sensor was used in in vitro experiments to monitor chemotherapeutic agent potency on drug-resistant and drug-sensitive cancer cell lines. Concentrations higher than 5 μM elicited cytotoxic effects on both cell lines, while a dose of 1 μM allowed discrimination of the two cell types. The system demonstrates the use of real-time capacitance measurements as a proof-of-concept tool that has potential to hasten the drug development process

Design and implementation of a multi-modal sensor with on-chip security

With the advancement of technology, wearable devices for fitness tracking, patient monitoring, diagnosis, and disease prevention are finding ways to be woven into modern world reality. CMOS sensors are known to be compact, with low power consumption, making them an inseparable part of wireless medical applications and Internet of Things (IoT). Digital/semi-digital output, by the translation of transmitting data into the frequency domain, takes advantages of both the analog and digital world. However, one of the most critical measures of communication, security, is ignored and not considered for fabrication of an integrated chip. With the advancement of Moore\u27s law and the possibility of having a higher number of transistors and more complex circuits, the feasibility of having on-chip security measures is drawing more attention. One of the fundamental means of secure communication is real-time encryption. Encryption/ciphering occurs when we encode a signal or data, and prevents unauthorized parties from reading or understanding this information. Encryption is the process of transmitting sensitive data securely and with privacy. This measure of security is essential since in biomedical devices, the attacker/hacker can endanger users of IoT or wearable sensors (e.g. attacks at implanted biosensors can cause fatal harm to the user). This work develops 1) A low power and compact multi-modal sensor that can measure temperature and impedance with a quasi-digital output and 2) a low power on-chip signal cipher for real-time data transfer

The potential of microelectrode arrays and microelectronics for biomedical research and diagnostics

Planar microelectrode arrays (MEAs) are devices that can be used in biomedical and basic in vitro research to provide extracellular electrophysiological information about biological systems at high spatial and temporal resolution. Complementary metal oxide semiconductor (CMOS) is a technology with which MEAs can be produced on a microscale featuring high spatial resolution and excellent signal-to-noise characteristics. CMOS MEAs are specialized for the analysis of complete electrogenic cellular networks at the cellular or subcellular level in dissociated cultures, organotypic cultures, and acute tissue slices; they can also function as biosensors to detect biochemical events. Models of disease or the response of cellular networks to pharmacological compounds can be studied in vitro, allowing one to investigate pathologies, such as cardiac arrhythmias, memory impairment due to Alzheimer's disease, or vision impairment caused by ganglion cell degeneration in the retin

Capteur d’hydrogène mos et méthode d’intégration à une technologie de transistor FDSOI

Abstract: hydrogen can be used as an energy carrier (storage) by the renewable energy industry as well as the automotive industry (fuel cell). Other industries already use hydrogen such, food processing and petroleum refineries. Hydrogen is odorless, transparent, and has a lower explosive limit of 4 %. Reliable, fast sensor are essential tools for a hydrogen safe environment. The work of this thesis provides a semiconductor-based hydrogen sensing solution. A MOS capacitor using a CMOS compatible novel Pt/Ti/ALD-Al2O3/p-Si stack. The Pt/Ti/Al2O3 sensing interface materials thicknesses are 100/5/38 nm respectively. The device can detect very low concentrations < 20 ppm. Furthermore, for a concentration of 500 ppm the response time is 56 s. the impact of testing conditions such temperature, and total gas flow have been studied. Results show that at 60℃ the device does not respond to hydrogen. And at 80℃ or higher the sensing response time is significantly reduced with increasing temperature. Furthermore, the total gas flow has an impact on the device response time and shows that a portion of the time response delay can be attributed to the chamber’s volume. Moreover, a heterogeneous integration method has been designed and presented. The latter represents a great tool for a flexible prototyping of sensors using FDSOI transistor technology. The integration has been simulated and results show promising results. The capacitive coupling feature in the FDSOI between the front and back gate is used to amplify the potential variation at the front gate. For instance, a 0.3 V hydrogen induced dipole potential can be amplified by a factor of 14 x.Le travail de cette thèse comprend la conception et la fabrication d’une technologie de capteur d’hydrogène basée sur une structure MOS. La structure est composée d’un empilement de Pt/Ti/Al2O3/p-Si. Les épaisseurs des matériaux utilisés pour la fabrication sont 100/5/38 nm (Pt/Ti/Al2O3) sur un substrat de silicium. Le capteur est capable de détecter de très faibles concentrations < 20 ppm. De plus, pour une concentration de 500 ppm, le temps de réponse est 56 s. L’impact de plusieurs conditions de test, comprenant la température et le débit total dans la chambre a été évalué. Les résultats montrent qu’à 60℃ le dispositive n’est pas capable de détecter la présence d’hydrogène. Cependant, à partir d’une température de 80℃, la réponse est très importante et le temps diminue pour encore des températures plus élevées. Le débit total dans la chambre a aussi démontré un impact sur le temps de réponse du capteur. Ce qui est aussi relié au volume de la chambre. Une intégration hétérogène ensuite a été conçue et présentée. Cette dernière est un outil flexible pour le prototypage avec des technologies de transistor FDSOI. L’intégration des deux dispositifs a été effectuée et montre de résultats prometteurs. Le couplage capacitif entre la grille avant et la grille arrière du transistor FDSOI permet d’amplifier le signal du capteur. Par exemple, une variation de potentiel de 0.3 V peut être amplifier par un facteur de 14 x, donc 4.19 V