Development of a Portable CMOS Time-Domain Fluorescence Lifetime Imager

Modern laboratory equipments to measure the excited-state lifetime of fluorophores usually include an expensive picosecond pulsed-laser excitation source, a fragile photomultiplier tube, and a large instrument body for optics. A portable and robust device to make fluorescence lifetime measurement in nanosecond scale is of great attraction for chemists and biologists. This dissertation reports the development of a portable LED time-domain fluorimeter from an all-solid-state discrete-component prototype to its advanced CMOS integrated circuit implementation. The motivation of the research is to develop a multiplexed fluorimeter for point-of-care diagnosis. Instruments developed by this novel method have higher fill factor, are more portable, and are fabricated at lower cost

Photodetectors

In this book some recent advances in development of photodetectors and photodetection systems for specific applications are included. In the first section of the book nine different types of photodetectors and their characteristics are presented. Next, some theoretical aspects and simulations are discussed. The last eight chapters are devoted to the development of photodetection systems for imaging, particle size analysis, transfers of time, measurement of vibrations, magnetic field, polarization of light, and particle energy. The book is addressed to students, engineers, and researchers working in the field of photonics and advanced technologies

A low-voltage CMOS-compatible time-domain photodetector, device & front end electronics

During the last decades, the usage of silicon photodetectors, both as stand-alone sensor or integrated in arrays, grew tremendously. They are now found in almost any application and any market range, from leisure products to high-end scientific apparatuses, including, among others, industrial, automotive, and medical equipment. The impressive growth in photodetector applications is closely linked to the development of CMOS technology, which now offers inexpensive and efficient analog and digi-tal signal processing capabilities. Detectors are often integrated with their respective front end and application-specific digital circuit on the same silicon die, forming complete systems on chip. In some cases the detector itself is not on the same chip but often part of the same package. However, this trend of co-integration of analog front end and digital circuits complicates the design of the analog part. The ever-decreasing supply voltage and the smaller transistors in advanced processes (which are driven by the development of digital cir-cuits) negatively impact the performance of the analog structures and complicates their design. For photodetector systems, the effect most importantly translates into a degradation of dynamic range and signal-to-noise ratio. One way to circumvent the problem of low supply voltages is to shift the operation from voltage domain to time domain. By doing so, the signal is no longer constrained by the supply rails and analog amplification is avoided. The signal takes the form of a time-based modulation, such as pulse-width modulation or pulse-frequency modulation. Another advantage is that the output signal of a time-domain photodetection system is directly interfaceable with digital circuits. In this work, a new type of CMOS-compatible photodetector displaying intrinsic light-to-time conversion is proposed. Its physical structure consists of a MOS gate interleaved with a PN junction. The MOS structure is acting as a photogate. The depletion region shrinks when photogenerated carriers fill the potential well. At some point, the anode of the PN structure is de-isolated from the rest of the detector and triggers a positive-feedback effect that leads to a very steep current increase through the PN-junction. This translates into a signal of very high amplitude and independent from light-intensity, which can be almost directly interfaced with digital circuits. This simplifies the front end circuit compared to photodiode-based systems. The physical behavior of the device is analyzed with the help of TCAD simulations and simple behavioral and shot-noise models are proposed. The device has been co-integrated with its driver and front end circuit in a standard CMOS process and its characteristics have been measured with a custom-made measurement system. The effect of bias parameters on the performance of the sensor are also analyzed. The limitations of the device are discussed, the most important ones being dark current and linearity. Techno-logical solutions, such as the implementation of the detector on Silicon-on-Insulator technology, are proposed to overcome the limitations. Finally, some application demonstrators have been realized. Other applications that could benefit from the detector are suggested, such as digital applications taking advantage of the latching behavior of the device, and a Photoplethysmography (PPG) system that uses a PLL-based control loop to minimize the emitting LED-current

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