Indirect test of M-S circuits using multiple specification band guarding

Testing analog and mixed-signal circuits is a costly task due to the required test time targets and high end technical resources. Indirect testing methods partially address these issues providing an efficient solution using easy to measure CUT information that correlates with circuit performances. In this work, a multiple specification band guarding technique is proposed as a method to achieve a test target of misclassified circuits. The acceptance/rejection test regions are encoded using octrees in the measurement space, where the band guarding factors precisely tune the test decision boundary according to the required test yield targets. The generated octree data structure serves to cluster the forthcoming circuits in the production testing phase by solely relying on indirect measurements. The combined use of octree based encoding and multiple specification band guarding makes the testing procedure fast, efficient and highly tunable. The proposed band guarding methodology has been applied to test a band-pass Butterworth filter under parametric variations. Promising simulation results are reported showing remarkable improvements when the multiple specification band guarding criterion is used.Peer ReviewedPostprint (author's final draft

Millimeter-Precision Laser Rangefinder Using a Low-Cost Photon Counter

In this book we successfully demonstrate a millimeter-precision laser rangefinder using a low-cost photon counter. An application-specific integrated circuit (ASIC) comprises timing circuitry and single-photon avalanche diodes (SPADs) as the photodetectors. For the timing circuitry, a novel binning architecture for sampling the received signal is proposed which mitigates non-idealities that are inherent to a system with SPADs and timing circuitry in one chip

Characterization of multiphase flows integrating X-ray imaging and virtual reality

Multiphase flows are used in a wide variety of industries, from energy production to pharmaceutical manufacturing. However, because of the complexity of the flows and difficulty measuring them, it is challenging to characterize the phenomena inside a multiphase flow. To help overcome this challenge, researchers have used numerous types of noninvasive measurement techniques to record the phenomena that occur inside the flow. One technique that has shown much success is X-ray imaging. While capable of high spatial resolutions, X-ray imaging generally has poor temporal resolution. This research improves the characterization of multiphase flows in three ways. First, an X-ray image intensifier is modified to use a high-speed camera to push the temporal limits of what is possible with current tube source X-ray imaging technology. Using this system, sample flows were imaged at 1000 frames per second without a reduction in spatial resolution. Next, the sensitivity of X-ray computed tomography (CT) measurements to changes in acquisition parameters is analyzed. While in theory CT measurements should be stable over a range of acquisition parameters, previous research has indicated otherwise. The analysis of this sensitivity shows that, while raw CT values are strongly affected by changes to acquisition parameters, if proper calibration techniques are used, acquisition parameters do not significantly influence the results for multiphase flow imaging. Finally, two algorithms are analyzed for their suitability to reconstruct an approximate tomographic slice from only two X-ray projections. These algorithms increase the spatial error in the measurement, as compared to traditional CT; however, they allow for very high temporal resolutions for 3D imaging. The only limit on the speed of this measurement technique is the image intensifier-camera setup, which was shown to be capable of imaging at a rate of at least 1000 FPS. While advances in measurement techniques for multiphase flows are one part of improving multiphase flow characterization, the challenge extends beyond measurement techniques. For improved measurement techniques to be useful, the data must be accessible to scientists in a way that maximizes the comprehension of the phenomena. To this end, this work also presents a system for using the Microsoft Kinect sensor to provide natural, non-contact interaction with multiphase flow data. Furthermore, this system is constructed so that it is trivial to add natural, non-contact interaction to immersive visualization applications. Therefore, multiple visualization applications can be built that are optimized to specific types of data, but all leverage the same natural interaction. Finally, the research is concluded by proposing a system that integrates the improved X-ray measurements, with the Kinect interaction system, and a CAVE automatic virtual environment (CAVE) to present scientists with the multiphase flow measurements in an intuitive and inherently three-dimensional manner

Development of Trigger and Control Systems for CMS

During the year of 2007, the Large Hadron Collider (LHC) and its four main detectors will begin operation with a view to answering the most pressing questions in particle physics. However before one can analyse the data produced to find the rare phenomena being looked for, both the detector and readout electronics must be thoroughly tested to ensure that the system will operate in a consistent way. The Compact Muon Solenoid (CMS) is one of the two general-purpose detectors at CERN. The tracking component of the design produces more data than any previous detector used in particle physics, with approximately ten million detector channels. The data from the detector is processed by the tracker Front End Driver (FED). The large data volume necessitated the development of a buffering and throttling system to prevent buffer overflow both on and off the detector. A critical component of this system is the APV emulator (APVe), which vetoes trigger decisions based on buffer status in the tracker. The commissioning of these components, along with a large part of the Timing, Trigger and Control (TTC) system is discussed, including the various modifications that were made to improve the robustness of the full system. Another key piece of the CMS electronics is the calorimeter trigger system, responsible for identifying âinteresting' physical events in a background of well-understood phenomena using calorimetric information. Calorimeter information is processed to identify various trigger objects by the Global Calorimeter Trigger (GCT). The first component of this system is the Source card, which has been developed to transfer data from the Regional Calorimeter Trigger (RCT) to the Leaf card, the processing engine of the GCT. The use of modern programmable logic with high speed optical links is discussed, emphasising its use for data concentration and the benefit it confers to the processing algorithms. Looking forward to Super-LHC, a possible addition to the CMS Level-1 trigger system is discussed, incorporating information from a new pixel detector with an alternative stacked geometry that allows the possibility of on-detector data rate reduction by means of a transverse momentum cut. A toy Monte Carlo was developed to study detector performance. Issues with high-speed reconstruction and the complications of on-detector data rate reduction are also discussed

CMOS SPAD-based image sensor for single photon counting and time of flight imaging

The facility to capture the arrival of a single photon, is the fundamental limit to the detection of quantised electromagnetic radiation. An image sensor capable of capturing a picture with this ultimate optical and temporal precision is the pinnacle of photo-sensing. The creation of high spatial resolution, single photon sensitive, and time-resolved image sensors in complementary metal oxide semiconductor (CMOS) technology offers numerous benefits in a wide field of applications. These CMOS devices will be suitable to replace high sensitivity charge-coupled device (CCD) technology (electron-multiplied or electron bombarded) with significantly lower cost and comparable performance in low light or high speed scenarios. For example, with temporal resolution in the order of nano and picoseconds, detailed three-dimensional (3D) pictures can be formed by measuring the time of flight (TOF) of a light pulse. High frame rate imaging of single photons can yield new capabilities in super-resolution microscopy. Also, the imaging of quantum effects such as the entanglement of photons may be realised. The goal of this research project is the development of such an image sensor by exploiting single photon avalanche diodes (SPAD) in advanced imaging-specific 130nm front side illuminated (FSI) CMOS technology. SPADs have three key combined advantages over other imaging technologies: single photon sensitivity, picosecond temporal resolution and the facility to be integrated in standard CMOS technology. Analogue techniques are employed to create an efficient and compact imager that is scalable to mega-pixel arrays. A SPAD-based image sensor is described with 320 by 240 pixels at a pitch of 8μm and an optical efficiency or fill-factor of 26.8%. Each pixel comprises a SPAD with a hybrid analogue counting and memory circuit that makes novel use of a low-power charge transfer amplifier. Global shutter single photon counting images are captured. These exhibit photon shot noise limited statistics with unprecedented low input-referred noise at an equivalent of 0.06 electrons. The CMOS image sensor (CIS) trends of shrinking pixels, increasing array sizes, decreasing read noise, fast readout and oversampled image formation are projected towards the formation of binary single photon imagers or quanta image sensors (QIS). In a binary digital image capture mode, the image sensor offers a look-ahead to the properties and performance of future QISs with 20,000 binary frames per second readout with a bit error rate of 1.7 x 10-3. The bit density, or cumulative binary intensity, against exposure performance of this image sensor is in the shape of the famous Hurter and Driffield densitometry curves of photographic film. Oversampled time-gated binary image capture is demonstrated, capturing 3D TOF images with 3.8cm precision in a 60cm range

고속 다중변수 세포기반 분석을 위한 코드화된 미세입자를 이용한 지역화된 바이러스 기반의 유전자 전달

학위논문 (박사)-- 서울대학교 대학원 : 전기·컴퓨터공학부, 2015. 8. 권성훈.In this dissertation, I develop an adenoviral vector-immobilised patch-type encoded microparticle for high-throughput, high-content cellular assays and name this encoded viral micropatch. This technology spatially confines the adenoviral gene delivery to only the cells under the micropatch by simply pipetting a heterogeneous mixture of the two-dimensional (2D) shape-coded viral micropatches on monolayer-cultured cells. Distinct clusters of transduced cells are then created in correspondence with the randomly positioned micropatches and the delivered gene into the cells within each cluster can be identified using the shape of the micropatch. For this purpose, shape-coded polymer microparticles are fabricated by photolithography, and highly localized gene delivery is achieved by specifically immobilizing adenoviral vectors on the microparticles. This unique feature allows high-throughput compound screening by virtue of multiplexing in a well of a standard microplate and creates no restriction for fluorescence-based assay formats with high-content imagers. To highlight the capabilities of this technology, I demonstrate a multiplex G-protein coupled receptor (GPCR) internalization assay that requires compound treatments followed by fluorescence-based target tracking at the sub-cellular level. First, I develop the maskless lithography system supporting an automated step-and-repeat operation for the fabrication of microparticles with various 2D graphical codes. Using this system, I explore new applications of the encoded microparticles and lithography technique such as anti-counterfeiting of drugs, parallel loading of small volume liquid for multiplexed bioassays, and conformal phosphor coating for white light-emitting diodes (LEDs). For the development of the encoded viral micropatch, various shape-coded microparticles are fabricated with carboxyl groups on the surfaces for specific immobilization of adenoviral vectors. The chemical functionalization is achieved by the incorporation of acrylic acid to photocurable polymer solution. Then, two adenoviral vector immobilization methods are developed with this shape-coded microparticle. The first method is to directly link the carboxyl groups on the microparticle and the primary amine groups on the surface proteins of adenoviral vectors using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) plus N-hydroxysulfosuccinimide (Sulfo-NHS) crosslinking reaction. The immobilization of adenoviral vectors in this approach is confirmed by an immunofluorescence test and a scanning electron microscope (SEM) observation. The second method utilizes an avidin-biotin interaction. In this approach, both the microparticles and adenoviral vectors are biotinylated using amine-activated and amine-reactive biotin reagents, respectively. Then, they are linked by the mediation of avidin. The immobilized adenoviral vectors are well observed using a SEM. The localized viral gene delivery of two types of the encoded viral micropatches is evaluated by transducing a human osteosarcoma cell line (U-2 OS) cultured in a standard 96-well microtiter plate. The first type of the encoded viral micropatch fabricated via EDC/Sulfo-NHS reaction shows low rate of the localization of gene delivery due to an escape of non-specifically bound adenoviral vectors. However, the second type of the encoded viral micropatch fabricated utilizing avidin-biotin interaction offers highly localized gene delivery. This is owing to the viral receptor-independent transduction of the biotinylated adenoviral vector, which is further supported by the transduction experiment of an adenovirus receptor-deficient cell line. Finally, I demonstrate a multiplexed GPCR internalization assay based on the localized gene delivery with the encoded viral micropatches. The development of high-throughput cell-based GPCR functional assays is very important for screening large compound libraries in the drug discovery process and ligand-induced receptor internalization assays have broad applicability to various GPCR subfamilies among several GPCR assay formats. However, high-content imaging is required for fluorescence-based intracellular measurement of receptor internalization. To address this issue, I fabricate three types of encoded viral micropatches with adenoviral vectors bearing green fluorescence protein (GFP)-tagged GPCR genes. Then, the responses of multiple GPCRs against one ligand treatment is acquired in one reaction site by achieving simultaneous expression of multiple GPCRs with the fabricated viral micropatches in a cell monolayer cultured in a well of a 96-well plate. High-content analysis of this micropatch-based multiplexed assay shows comparable results in the receptor internalization with the conventional singlet assay using free adenoviral vectors while reducing the number of pipetting actions.Abstract i Contents v List of Figures viii List of Tables xvii Chapter 1 Introduction 1 1.1 Cell-based Assays in Drug Discovery 4 1.2 Image-based High-content Screening 7 1.3 Cell Microarray for High-throughput Screening 10 1.4 Main Concept: Encoded Viral Micropatch 12 Chapter 2 Development of Encoded Viral Micropatch 15 2.1 Introduction 16 2.2 Fabrication of Encoded Microparticles 19 2.2.1 Maskless Lithography System 19 2.2.2 Shape-coded Microparticles for Encoded Viral Micropatch 32 2.3 Immobilization of Viral Vectors 37 2.3.1 Recombinant Adenoviral Vector 37 2.3.2 Direct Targeting of Viral Capsid via Carbodiimide Crosslinker (Type 1 Encoded Viral Micropatch) 39 2.3.3 Indirect Targeting of Biotin-tethered Viral Capsid via Avidin (Type 2 Encoded Viral Micropatch) 44 2.4 Conclusion 52 Chapter 3 Localized Viral Gene Delivery 53 3.1 Introduction 54 3.2 Localized Gene Delivery with Type 1 Encoded Viral Micropatch 57 3.3 Localized Gene Delivery with Type 2 Encoded Viral Micropatch 60 3.3.1 Evaluation of the Localized Gene Delivery 60 3.3.2 Consideration of the Localized Gene Delivery 65 3.3.3 Transduction of an Adenoviral Receptor-deficient Cell Line 67 3.3.4 Transduction Efficiency of the Encoded Viral Micropatch 69 3.4 Conclusion 74 Chapter 4 Multiplex GPCR Internalization Assay 75 4.1 G Protein-coupled Receptor (GPCR) 77 4.2 Materials for the Assay 79 4.2.1 GPCR Adenoviral Vectors 79 4.2.2 Ligands 79 4.2.3 Cell Culture 79 4.3 Conventional GPCR Internalization Assay 80 4.3.1 Assay Procedure 80 4.3.2 Assay Result 83 4.4 Multiplex GPCR Internalization Assay 85 4.4.1 Preparation of Encoded Viral Micropatches 85 4.4.2 Assay Procedure 85 4.4.3 Assay Result 87 4.5 Conclusion 91 Conclusion 92 Bibliography 94 국문 초록 103Docto

Millimeter-Precision Laser Rangefinder Using a Low-Cost Photon Counter

In this book we successfully demonstrate a millimeter-precision laser rangefinder using a low-cost photon counter. An application-specific integrated circuit (ASIC) comprises timing circuitry and single-photon avalanche diodes (SPADs) as the photodetectors. For the timing circuitry, a novel binning architecture for sampling the received signal is proposed which mitigates non-idealities that are inherent to a system with SPADs and timing circuitry in one chip

Optimising the NAOMI adaptive optics real-time control system

This thesis describes the author's research in the field of Real-Time Control (RTC) for Adaptive Optics (AO) instrumentation. The research encompasses experiences and knowledge gained working in the area of RTC on astronomical instrumentation projects whilst at the Optical Science Laboratories (OSL), University College London (UCL), the Isaac Newton Groups of Telescopes (ING) and the Centre for Advanced Instrumentation (СfAI), Durham University. It begins by providing an extensive introduction to the field of Astronomical Adaptive Optics covering Image Correction Theory, Atmospheric Theory, Control Theory and Adaptive Optics Component Theory. The following chapter contains a review of the current state of world wide AO instruments and facilities. The Nasmyth Adaptive Optics Multi-purpose Instrument (NAOMI), the common user AO facility at the 4.2 William Herschel Telescope (WHT), is subsequently described. Results of NAOMI component characterisation experiments are detailed to provide a system understanding of the improvement optimisation could offer. The final chapter investigates how upgrading the RTCS could increase NAOMI'S spatial and temporal performance and examines the RTCS in the context of Extremely Large Telescope (ELT) class telescopes