A portable device for time-resolved fluorescence based on an array of CMOS SPADs with integrated microfluidics

[eng] Traditionally, molecular analysis is performed in laboratories equipped with desktop instruments operated by specialized technicians. This paradigm has been changing in recent decades, as biosensor technology has become as accurate as desktop instruments, providing results in much shorter periods and miniaturizing the instrumentation, moving the diagnostic tests gradually out of the central laboratory. However, despite the inherent advantages of time-resolved fluorescence spectroscopy applied to molecular diagnosis, it is only in the last decade that POC (Point Of Care) devices have begun to be developed based on the detection of fluorescence, due to the challenge of developing high-performance, portable and low-cost spectroscopic sensors. This thesis presents the development of a compact, robust and low-cost system for molecular diagnosis based on time-resolved fluorescence spectroscopy, which serves as a general-purpose platform for the optical detection of a variety of biomarkers, bridging the gap between the laboratory and the POC of the fluorescence lifetime based bioassays. In particular, two systems with different levels of integration have been developed that combine a one-dimensional array of SPAD (Single-Photon Avalanch Diode) pixels capable of detecting a single photon, with an interchangeable microfluidic cartridge used to insert the sample and a laser diode Pulsed low-cost UV as a source of excitation. The contact-oriented design of the binomial formed by the sensor and the microfluidic, together with the timed operation of the sensors, makes it possible to dispense with the use of lenses and filters. In turn, custom packaging of the sensor chip allows the microfluidic cartridge to be positioned directly on the sensor array without any alignment procedure. Both systems have been validated, determining the decomposition time of quantum dots in 20 nl of solution for different concentrations, emulating a molecular test in a POC device.[cat] Tradicionalment, l'anàlisi molecular es realitza en laboratoris equipats amb instruments de sobretaula operats per tècnics especialitzats. Aquest paradigma ha anat canviant en les últimes dècades, a mesura que la tecnologia de biosensor s'ha tornat tan precisa com els instruments de sobretaula, proporcionant resultats en períodes molt més curts de temps i miniaturitzant la instrumentació, permetent així, traslladar gradualment les proves de diagnòstic fora de laboratori central. No obstant això i malgrat els avantatges inherents de l'espectroscòpia de fluorescència resolta en el temps aplicada a la diagnosi molecular, no ha estat fins a l'última dècada que s'han començat a desenvolupar dispositius POC (Point Of Care) basats en la detecció de la fluorescència, degut al desafiament que suposa el desenvolupament de sensors espectroscòpics d'alt rendiment, portàtils i de baix cost. Aquesta tesi presenta el desenvolupament d'un sistema compacte, robust i de baix cost per al diagnòstic molecular basat en l'espectroscòpia de fluorescència resolta en el temps, que serveixi com a plataforma d'ús general per a la detecció òptica d'una varietat de biomarcadors, tancant la bretxa entre el laboratori i el POC dels bioassaigs basats en l'anàlisi de la pèrdua de la fluorescència. En particular, s'han desenvolupat dos sistemes amb diferents nivells d'integració que combinen una matriu unidimensional de píxels SPAD (Single-Photon Avalanch Diode) capaços de detectar un sol fotó, amb un cartutx microfluídic intercanviable emprat per inserir la mostra, així com un díode làser UV premut de baix cost com a font d'excitació. El disseny orientat a la detecció per contacte de l'binomi format pel sensor i la microfluídica, juntament amb l'operació temporitzada dels sensors, permet prescindir de l'ús de lents i filtres. Al seu torn, l'empaquetat a mida de l'xip sensor permet posicionar el cartutx microfluídic directament sobre la matriu de sensors sense cap procediment d'alineament. Tots dos sistemes han estat validats determinant el temps de descomposició de "quantum dots" en 20 nl de solució per a diferents concentracions, emulant així un assaig molecular en un dispositiu POC

Optical signal processing for efficient information networks

With the internet and rise of personal electronics there is an ever increasing amount of data collected and transmitted every day; modern communication systems will soon be overwhelmed. The driving force behind the demand is an increasing speed of signal acquisition, in the public domain, as well as medicine and industry; newer technologies allow massive amounts of data produced through text, voice, and video. This puts strain on both signal acquisition systems and communications systems to increase the total information flow. Transmission down fiber links is enabled by the large but limited bandwidth of optical fiber, and as we look toward the future, efficient use of the available optical bandwidth is paramount. I apply the large bandwidth of fiber and ultrafast speed of nonlinear optics to solve these problems, implementing high-speed and efficient signal acquisition and communication systems. With the increased volume of information being transferred, compression of data has become essential to allow multimedia communication. Data is acquired then compressed and transmitted, requiring massive computing power. Using the information theory technique coined “compressed sensing”, we demonstrate real time compression at signal acquisition, removing a timeconsuming and bandwidth inefficient step in a complete communication link. I use dispersion and nonlinear wave mixing in optical fiber, and gigahertz electro-optics to shape light at terahertz speeds, reaching towards the limit of compressed image acquisition. To complete a high-speed communications link, I investigate the use of Nyquist optical time division multiplexing to maximize spectral efficiency. The square spectral shape of a Nyquist pulse is ideal, but the pulse ripples on forever in the time domain, presenting problems for demultiplexing Nyquist signals at the receiver. I present a solution using coherent detection with a biorthogonal Nyquist pulse to eliminate interference from neighboring channels, and implement a proof of concept system using nonlinear wave mixing. Stable clock transfer is essential for coherent communication, but environmental fluctuations erode clock information, reducing the effective data rate of the communications channel. I present a versatile solution for stable time and frequency transfer using dispersion and nonlinear wave mixing in optical fiber

The G0 Experiment: Apparatus for Parity-Violating Electron Scattering Measurements at Forward and Backward Angles

In the G0 experiment, performed at Jefferson Lab, the parity-violating elastic scattering of electrons from protons and quasi-elastic scattering from deuterons is measured in order to determine the neutral weak currents of the nucleon. Asymmetries as small as 1 part per million in the scattering of a polarized electron beam are determined using a dedicated apparatus. It consists of specialized beam-monitoring and control systems, a cryogenic hydrogen (or deuterium) target, and a superconducting, toroidal magnetic spectrometer equipped with plastic scintillation and aerogel Cerenkov detectors, as well as fast readout electronics for the measurement of individual events. The overall design and performance of this experimental system is discussed.Comment: Submitted to Nuclear Instruments and Method

Novel scanning techniques for CCD image capture and display

This work details two investigations into image capture, taken from the fields of x-ray and laser research, and also details two scanning systems: a wire surface generator and a video security device. Firstly a camera system is described that can display images, digitize them and provide real time false shading. This camera is shown to have a linear intensity response and to have a maximum saturation level below the digitizing range. Some example outputs are then illustrated. The ability to irradiate CCDs with direct X-ray radiation is also investigated. A camera is developed that vertically integrates such images and is shown to give an increase in the processing speed of existing equipment and to reduce experiment times by a factor of 388. Taking this idea further, a fast one dimensional camera is developed. This camera couples laser pulses onto a CCDs via a fibre optic faceplate and a 25 mum slit. Unusual scanning techniques are used to achieve image storage within the sensor itself and a method for correcting dark current and other errors is proposed. Next a mechanism for displaying wire surface representations of intensity) images is investigated. Results obtained from real time, hidden line removing hardware are illustrated, along with improved algorithms for shaded surface generation. This is then developed into a security device protecting VDUs from radio based surveillance. This is achieved by randomizing the display order of raster lines along with a hardware solution for random sequence generation. Finally the generation of Uniformly distributed random numbers is achieved by processing readings from a digitized. Normally distributed voltage source. The effects of this processing are investigated and an analysis of the underlying theory is used to determine an optimal setting for the gain stage

NASA Tech Briefs, December 1988

This month's technical section includes forecasts for 1989 and beyond by NASA experts in the following fields: Integrated Circuits; Communications; Computational Fluid Dynamics; Ceramics; Image Processing; Sensors; Dynamic Power; Superconductivity; Artificial Intelligence; and Flow Cytometry. The quotes provide a brief overview of emerging trends, and describe inventions and innovations being developed by NASA, other government agencies, and private industry that could make a significant impact in coming years. A second bonus feature in this month's issue is the expanded subject index that begins on page 98. The index contains cross-referenced listings for all technical briefs appearing in NASA Tech Briefs during 1988

NASA Tech Briefs, May 1989

This issue contains a special feature on the flight station of the future, discussing future enhancements to Aircraft cockpits. Topics include: Electronic Components and Circuits. Electronic Systems, Physical Sciences, Materials, Computer Programs, Mechanics, Machinery, Fabrication Technology, and Mathematics and Information Sciences

NASA Tech Briefs, June 1989

Topics include: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences

Particle Physics Reference Library

This second open access volume of the handbook series deals with detectors, large experimental facilities and data handling, both for accelerator and non-accelerator based experiments. It also covers applications in medicine and life sciences. A joint CERN-Springer initiative, the “Particle Physics Reference Library” provides revised and updated contributions based on previously published material in the well-known Landolt-Boernstein series on particle physics, accelerators and detectors (volumes 21A,B1,B2,C), which took stock of the field approximately one decade ago. Central to this new initiative is publication under full open access