Title Promoter Affiliations Abstract "Image sensors enabling fluorescence-lifetime guided surgery" "Maarten Kuijk" "Clinical sciences, Electronics and Informatics" "Surgery remains an effective treatment for many cancers and is often the only curative treatment option. During surgery, it is very important that all malignant tissue is removed but also that vital structures are left intact. Recognizing the malignant tissue is not always obvious and metastases can be left undetected. To guarantee safe and complete removal, it would be of major benefit to a surgeon to have some kind of guidance. This guidance could be made possible with fluorescent contrast agents that can selectively light-up the cancerous tissue. Such contrast agents are currently emerging and, in particular, near-infrared nanobody-based tracers are being developed at the VUB ICMI department by the group of Prof. Hernot. These tracers have the benefit that they are very specific, quickly reach their target and emit light in the near infrared spectrum that can penetrate deeper through tissue. This project aims at researching novel image sensors to capture that fluorescence emission and to be used in future fluorescence guided surgery systems. Our image sensors will be capable of not only detecting the fluorescence intensity but also the specific fluorescence lifetime. The fluorescence lifetime is needed to separate the useful signal from the background but today no image sensors exist that have the necessary low-noise and efficiency characteristics." "High-performance CMOS image sensors for low-flux applications" "Hans Van Winckel" Astronomy "The main objective of this thesis is to investigate important performance parameters of a monolithic CMOS image sensor that are more relevant for astronomical applications, such as non-linearity, saturation, conversion gain, dynamic range, noise, dark current, full well capacity and their temperature dependency, crosstalk, MTF and image persistence. We also aim to determine the importance of all these parameters for scientific imaging, specific to astronomy. Another objective is to measure the intra-pixel sensitivity variation (IPSV). IPSV is specifically important for space photometry and has undergone a continuous study during the past decade for CCDs and hybrid CMOS detectors, but so far, few studies have been done on CMOS image sensors. We present a forward modeling analysis to derive the intra pixel sensitivity variation and report the measurement of the sub-pixel sensitivity variation. Finally, we aim to test the CMOS image sensor performance at the Mercator telescope with real astronomical targets, which gives an opportunity to test and find out the existing drawbacks in our CMOS detector for astronomy. This objective includes the design and development of a CMOS camera to mount on the 1.2m Mercator telescope at the Roque de los Muchachos observatory in La Palma, Spain." "Novel pixel-circuits allowing implementation of Video-Rate MegaPixel Fluorescence-Lifetime Image Sensors" "Maarten Kuijk" "Electronics and Informatics, Faculty of Engineering" "Fluorescence lifetime of molecules can be considered as an additional color, revealing crucial invisible information in a large range of applications, spanning from microscopy of biological cells to image guided surgery. Users are longing for cameras that can image this fluorescence lifetime at a high resolution and at video-rate speed. The detector of choice to achieve this is the Single-Photon Avalanche Diode (SPAD) because it can deliver directly a digital output that includes the precious time-of-arrival (ToA) of each received photon. Current state-of-the-art systems communicate these received ToAs from the sensor to an external processor for computing the lifetime estimation. However, more than thousands of ToAs/pixel/frame are required for good accuracy and precision. For mega-pixel-resolution at video-rate operation, data congestion forms however an imminent showstopper. In the project we will use an elegant in-pixel, partly analog circuit, to provide for a lifetime estimation method that only occupies a small silicon area, supports good fill-factor, low power operation, and that has a large dynamic range for the incoming fluorescence light. The uncalibrated sensor output is targeted to deliver direct information with better than 3% precision for lifetimes down to ~300ps, being sufficient for most foreseeable applications." "Two Photon Absorption (TPA) in CMOS image sensors" "Guy Meynants, Paul Leroux" "Electronic Circuits and Systems (ECS)" "The project aims to investigate whether CMOS image sensors can be used for the detection of light and images in the wavelength range between 1050 nm and 1550 nm using two-photon absorption (“TPA”). Due to the strong advances in laser technology and the low read-out noise achievable with modern image sensors, this could potentially be an alternative to cooled detectors based on more exotic materials in practical applications." "Platform for advanced 3D-Stacked Image Sensors (3SIS)." "Georges Gielen" "ESAT - MICAS, Microelectronics and Sensors" "The goal of this SBO project is to develop a generic platsorm consisting of both process technology modules as well as design techniques to enable a multitude of future silicon-based image sensor applications." "Effects of radiation on state-of-the-art CMOS image sensors" "Guy Meynants" "Electronic Circuits and Systems (ECS)" "A lot of progress has been made on the understanding of radiation effects on CMOS image sensors (CIS). However, this is limited to pixels operating in a “rolling shutter” mode and with a classic 3-transistor or 4-transistor pixel topology. Meanwhile many new process steps were introduced in CIS technology which have effects on radiation tolerance (like backside illumination or deep trench isolation) and several new pixel architectures have been proposed, like global shutter pixels and pixels for Time-of-Flight (TOF) 3D imaging. Little is known yet on the radiation tolerance of devices using these latest technologies. This project aims to perform the first steps in radiation assessment of these latest generation of pixel architectures and CIS technologies, based upon standard devices. It hopes to trigger follow-on projects in the field of global shutter and time-of-flight imagers." "Photon Counting CMOS Image Sensors" "Guy Meynants" "Electronic Circuits and Systems (ECS)" "CMOS image sensors have reached such low noise levels that photon counting becomes possible, even without avalanche photodiodes. Several groups have published papers and developed products that show histograms at low light levels with discrete peaks at one, two or three detected photo-electrons.  These pixels employ regular 4-transistor active pixels but with a large in-pixel gain, mostly by scaling down the floating diffusion capacitance. However, this comes at the cost of a low full well capacity, which consequently limits the dynamic range of the pixel.Recently, single-photon avalanche photodiodes have also been demonstrated for imaging with virtually zero read noise.  Each pixel contains a SPAD and an 11-bit counter, enabling 11-bit dynamic range and zero read noise. But the SPAD features a dead time during quenching and is difficult to scale further in size.In this research, we will investigate more advanced pixel circuits that allow to detect small charge packets in the pixel without avalanche diode, and without dynamic range limitations." "Platform for Advanced 3D-Stacked Image Sensors (3SIS)" "The goal of this project is to develop a generic platform consisting of both process technology modules as well as design techniques to enable a multitude of future silicon-based image sensor applications." "SPECTRAI - Spectral image Processing with Efficiently Compressed TensoRs and AI" "Wouter Saeys" "Mechatronics, Biostatistics and Sensors (MeBioS), Declarative Languages and Artificial Intelligence (DTAI), Numerical Analysis and Applied Mathematics (NUMA)" "Artificial Intelligence (AI), and especially convolutional neural networks (CNNs), has revolutionized the way images are processed thanks to their unique architecture involving many parameters, and the availability of massive amounts of labelled images for parameter estimation. Spectral imagers provide a fingerprint for each pixel, revealing important quality information that cannot be assessed with RGB cameras. This offers great added potential for quality control in agrofood. Despite their potential, spectral imagers also bring a high complexity and data dimensionality. In combination with the general unavailability of large, labelled datasets this requires strategic basic research into efficient learning strategies that allow to build, maintain and transfer efficient processing pipelines for analyzing these complex data structures with a limited number of labelled images." "NIR-Sensitivity-Enhanced Gated Image Sensor for Fluorescence Lifetime Imaging Microscopy (FLIM)" "Chris Van Hoof" "Quantum Solid State Physics (QSP), Electronic Circuits and Systems (ECS)" "Because of the deep tissue penetration and the lower influence from the autofluorescence background, fluorescence lifetime imaging microscopy (FLIM) in the near-infrared (NIR) range becomes attractive for bioimaging. However, to reconstruct the fluorescence decay profile with the time-resolved technique, repetitive short excitation pulses are required, and a large number of light exposures easily result in the photobleaching of the fluorophores or the damage of the specimen, which normally is an irreversible process. In addition, parasitic light sensitivity (PLS) also has a significant impact on the FLIM signal-to-noise ratio. Therefore, this work is focused on the design and characterization of a silicon-based CMOS image sensor with high photon acquisition efficiency, high light sensitivity, and low PLS in the NIR range for obtaining accurate and precise FLIM data with low specimen damage.In this work, a system performance analysis of wide-field time-gated FLIM using three-tap gated CMOS image sensors is firstly utilized to provide an insight into incident photon conditions and image sensor properties required for achieving good FLIM. The results indicate that the external quantum efficiency (EQE), photo-charge collection speed, dark current, and PLS of the detector are all important for the FLIM measurement quality. For the NIR wavelength detection, the EQE and the PLS can be most problematic due to the low absorption in the silicon, or in other words, the longer silicon penetration depth. Therefore, to comprehensively consider these factors in the design, a backside illumination (BSI) image sensor with 15 µm pixel pitch and three transfer gates was designed on a 30 µm silicon substrate for better NIR light absorption. In addition, a p+ pinning layer is equipped at the photodiode and storage (STO) surfaces to decrease the dark current. A multi-step processing p-well funnel is applied to insulate the STOs for reducing the PLS and accelerating the photoelectron collection. Furthermore, a backside bias and a series of simulations are implemented to obtain optimal photo-charge transfer speed.This work used two phases to study the three-tap gated image sensor design. In the first phase, the structure and the configuration of the pixel were defined. The gating function and the electron transfer capability were simulated and verified with the TCAD. The characterization result of the initial device shows that the photoelectrons can be successfully transferred to the STOs using the gating operation. The characterization results reveal that the three STOs have similar behaviour, and no image lag is observed. The gating function of the transfer gates was also verified. The signal transfer rate with a 3.1 ns gating window presents a comparable result to the continuous mode.In the second phase, a series of DOEs is studied in order to optimize the process conditions and layout design for improving photo-charge collection speed. However, to adapt to the problematic substrate discovered in the initial device, the deepest p-well implantation of the p-well funnel was omitted to mitigate premature punch-through. Additionally, DOE was used to reduce the required backside bias needed for full depletion and monotonous electrostatic profile. The modified conditions were utilized during the processing of the second test vehicle. The back-grid shape is inspected during the process, and a clear pattern is confirmed. According to the measurement and the simulation results, the second device was found to exhibit a thicker n-doping layer than the original device. This may originate from tolerances of the substrate design used for device processing, unbeknownst at the time of development. This implies that the device is fabricated on a substrate with the correct condition so that the -10 V backside bias can be applied. This design shows similar properties in the three STOs with about 4.4 e- read noise and 1.8 e- pixel FPN. No observable image lag is measured, and the PRNU is on average 1.45%. A very good EQE of 67.5% and 52.5% at 780 nm and 905 nm wavelength was confirmed. The device’s PLS exhibits -70 dB at 780 nm and -61 dB at 905 nm. A 17 ns collection time of 90% generated photoelectrons (τp = 7.4 ns) is measured. The slow transport is verified to be dominated by the charge movement around the p-well. A high dark current is observed in the device while the transfer gate is opened. Based on the activation energy histogram and the SRP analysis of the backside surface, the BSI process is assumed to contribute significantly to the device.This developed image sensor performs a remarkable EQE in the NIR range compared to time-gated imaging including the commercial cameras in FLIM applications. It also achieves a comparable performance of 42% EQE at 940 nm to the state-of-the-art of time-resolved image sensors in time-of-flight (ToF) applications. Theoretically, the thick substrate of this device can provide good PLS compared to the devices for the ToF applications, which generally have thinner silicon substrates. The impulse response function of 7.4 ns of this design should be already sufficient for several types of NIR fluorophores, such as quantum dots or doped nanoparticles, fluorescing with a lifetime ranging from tens of nanosecond to microseconds. In future work, the further improved pixel speed should enable a wider lifetime range of NIR FLIM measurement.The second-generation design was utilized to build a FLIM demo setup. The setup was cooled to 2 °C to mitigate dark current. The background dark noise was subtracted for the lifetime reconstruction measurement by use of dark reference frames. A Qdot® 705 quantum dot solution was measured to exhibit a 131.7 ns fluorescence lifetime showing good matching to the expected literature value of 131 ns."