High-Speed Wide-Field Time-Correlated Single-Photon Counting Fluorescence Lifetime Imaging Microscopy

Fluorescence microscopy is a powerful imaging technique used in the biological sciences to identify labeled components of a sample with specificity. This is usually accomplished through labeling with fluorescent dyes, isolating these dyes by their spectral signatures with optical filters, and recording the intensity of the fluorescent response. Although these techniques are widely used, fluorescence intensity images can be negatively affected by a variety of factors that impact the fluorescence intensity. Fluorescence lifetime imaging microscopy (FLIM) is an imaging technique that is relatively immune to intensity fluctuations and also provides the unique ability to directly monitor the microenvironment surrounding a fluorophore. Despite the benefits associated with FLIM, the applications to which it is applied are fairly limited due to long image acquisition times and high cost of traditional hardware. Recent advances in complementary metal-oxide-semiconductor (CMOS) single-photon avalanche diodes (SPADs) have enabled the design of low-cost imaging arrays that are capable of recording lifetime images with acquisition times greater than one order of magnitude faster than existing systems. However, these SPAD arrays have yet to realize the full potential of the technology due to limitations in their ability to handle the vast amount of data generated during the commonly used time-correlated single-photon counting (TCSPC) lifetime imaging technique. This thesis presents the design, implementation, characterization, and demonstration of a high speed FLIM imaging system. The components of this design include a CMOS imager chip in a standard 0.13 μm technology containing a custom CMOS SPAD, a 64-by-64 array of these SPADs, pixel control circuitry, independent time-to-digital converters (TDCs), a FLIM specific datapath, and high bandwidth output buffers. In addition to the CMOS imaging array, a complete system was designed and implemented using a printed circuit board (PCB) for capturing data from the imager, creating histograms for the photon arrival data using field-programmable gate arrays, and transferring the data to a computer using a cabled PCIe interface. Finally, software is used to communicate between the imaging system and a computer.The dark count rate of the SPAD was measured to be only 231 Hz at room temperature while maintaining a photon detection probability of up to 30\%. TDCs included on the array have a 62.5 ps resolution and a 64 ns range, which is suitable for measuring the lifetime of most biological fluorophores. Additionally, the on-chip datapath was designed to handle continuous data transfers at rates capable of supporting TCSPC-based lifetime imaging at 100 frames per second. The system level implementation also provides sufficient data throughput for transferring up to 750 frames per second from the imaging system to a computer. The lifetime imaging system was characterized using standard techniques for evaluating SPAD performance and an electrical delay signal for measuring the TDC performance. This thesis concludes with a demonstration of TCSPC-FLIM imaging at 100 frames per second -- the fastest 64-by-64 TCSPC FLIM that has been demonstrated. This system overcomes some of the limitations of existing FLIM systems and has the potential to enable new application domains in dynamic FLIM imaging

Analysis and Design of Radio Frequency Integrated Circuits for Breast Cancer Radar Imaging in CMOS Technology

Breast cancer is by far the most incident tumor among female population. Early stage prevention is a key factor in delivering long term survival of breast cancer patients. X-ray mammography is the most commonly used diagnostic technique to detect non-palpable tumors. However, 10-30% of tumors are missed by mammography and ionizing radiations together with breast compression do not lead to comfort in patient treatment. In this context, ultrawideband microwave radar technology is an attractive alternative. It relies on the dielectric contrast of normal and malignant tissues at microwave frequencies to detect and locate tumors inside the breast. This work presents the analysis and design of radio frequency integrated circuits for breast cancer imaging in CMOS technology. The first part of the thesis concerns the system analysis. A behavioral model of two different transceiver architectures for UWB breast cancer imaging employing a SFCW radar system are presented. A mathematical model of the direct conversion and super heterodyne architectures together with a numerical breast phantom are developed. FDTD simulations data are used to on the behavioral model to investigate the limits of both architectures from a circuit-level point of view. Insight is given into I/Q phase inaccuracies and their impact on the quality of the final reconstructed images. The result is that the simplicity of the direct conversion architecture makes the receiver more robust toward the critical impairments for this application. The second part of the thesis is dedicated to the circuit design. The main achievement is a 65nm CMOS 2-16GHz stepped frequency radar transceiver for medical imaging. The RX features 36dB conversion gain, >29dBm compression point, 7dB noise figure, and 30Hz 1/f noise corner. The TX outputs 14dBm with >40dBc harmonic rejection and <109dBc/Hz phase noise at 1MHz offset. Overall power dissipation is 204mW from 1.2V supply. The radar achieves 3mm resolution within the body, and 107dB dynamic range, a performance enabling the use for breast cancer diagnostic imaging. To further assess the capabilities of the proposed radar, a physical breast phantom was synthesized and two targets mimicking two tumors were buried inside the breast. The targets are clearly identified and correctly located, effectively proving the performance of the designed radar as a possible tool for breast cancer detection

Pioneer F/G: Spacecraft Operational Characteristics

The Pioneer F/G Spacecraft Operational Characteristics Study was performed by TRWS systems Group for the National Aeronautics and Space Administration, Ames Research Center (NASA/ARC) between Novembe1970 and April 1971, under contract NAS2-6255. The purpose of this study is to describe the operational characteristics of the Pioneer F and G spacecraft system and its subsystems to the NASA/ARC Pioneer Project personnel having the responsibility for conducting the Pioneer F/G flight mission operations. This report, "Pioneer F/G Spacecraft Operational Characteristics," is the final report of this study

CMOS Hyperbolic Sine ELIN filters for low/audio frequency biomedical applications

Hyperbolic-Sine (Sinh) filters form a subclass of Externally-Linear-Internally-Non- Linear (ELIN) systems. They can handle large-signals in a low power environment under half the capacitor area required by the more popular ELIN Log-domain filters. Their inherent class-AB nature stems from the odd property of the sinh function at the heart of their companding operation. Despite this early realisation, the Sinh filtering paradigm has not attracted the interest it deserves to date probably due to its mathematical and circuit-level complexity. This Thesis presents an overview of the CMOS weak inversion Sinh filtering paradigm and explains how biomedical systems of low- to audio-frequency range could benefit from it. Its dual scope is to: consolidate the theory behind the synthesis and design of high order Sinh continuous–time filters and more importantly to confirm their micro-power consumption and 100+ dB of DR through measured results presented for the first time. Novel high order Sinh topologies are designed by means of a systematic mathematical framework introduced. They employ a recently proposed CMOS Sinh integrator comprising only p-type devices in its translinear loops. The performance of the high order topologies is evaluated both solely and in comparison with their Log domain counterparts. A 5th order Sinh Chebyshev low pass filter is compared head-to-head with a corresponding and also novel Log domain class-AB topology, confirming that Sinh filters constitute a solution of equally high DR (100+ dB) with half the capacitor area at the expense of higher complexity and power consumption. The theoretical findings are validated by means of measured results from an 8th order notch filter for 50/60Hz noise fabricated in a 0.35μm CMOS technology. Measured results confirm a DR of 102dB, a moderate SNR of ~60dB and 74μW power consumption from 2V power supply

Proceedings of the Second Caltech Conference on Very Large Scale Integration, held at the California Institute of Technology 19-21 January, 1981 ; Organized by the Caltech Computer Science Department and the Caltech Industrial Associates Office, and sponsored by Caltech Industrial Associates and the National Science Foundation

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MATLAB

A well-known statement says that the PID controller is the "bread and butter" of the control engineer. This is indeed true, from a scientific standpoint. However, nowadays, in the era of computer science, when the paper and pencil have been replaced by the keyboard and the display of computers, one may equally say that MATLAB is the "bread" in the above statement. MATLAB has became a de facto tool for the modern system engineer. This book is written for both engineering students, as well as for practicing engineers. The wide range of applications in which MATLAB is the working framework, shows that it is a powerful, comprehensive and easy-to-use environment for performing technical computations. The book includes various excellent applications in which MATLAB is employed: from pure algebraic computations to data acquisition in real-life experiments, from control strategies to image processing algorithms, from graphical user interface design for educational purposes to Simulink embedded systems

Skylab Operations Handbook Command/Service Modules CSM 116 Thru 118

The SKYLAB Operations Handbook (SOH) is a contractual document. The SOH (Volume 1) is system-oriented and not specifically designed for utilization by any special group. Volume 1 is the description portion of the SOH. It provides the description of all Command-Service Module (CSM) systems