Fluorescence lifetime sensing using time correlated single photon counting (TCSPC) is a key analytical tool for molecular and cell biology research, medical diagnosis and pharmacological development. However, commercially available TCSPC equipment is bulky, expensive and power hungry, typically requiring iterative software post-processing to calculate the fluorescence lifetime. Furthermore, the technique is restrictively slow due to a low photon throughput limit which is necessary to avoid distortions caused by TCSPC pile-up. An investigation into CMOS compatible multimodule architectures to miniaturise the standard TCSPC set up, allow an increase in photon throughput by overcoming the TCSPC pile-up limit, and provide fluorescence lifetime calculations in real-time is presented. The investigation verifies the operation of the architectures and leads to the selection of optimal parameters for the number of detectors and timing channels required to overcome the TCSPC pile-up limit by at least an order of magnitude. The parameters are used to implement a low power miniaturised sensor in a 130 nm CMOS process, combining single photon detection, multiple channel timing and embedded pre-processing of the fluorescence lifetime, all within a silicon area of < 2 mm2. Single photon detection is achieved using an array of single photon avalanche diodes (SPADs) arranged in a digital silicon photomultiplier (SiPM) architecture with a 10 % fill-factor and a compressed 250 ps output pulse, which provides a photon throughput of > 700 MHz. An array of time-interleaved time-to-digital converters (TI-TDCs) with 50 ps resolution and no processing dead-time records up to eight photon events during each excitation period, significantly reducing the effect of TCSPC pile-up. The TCSPC data is then processed using an embedded centre-of-mass method (CMM) pre-calculation to produce single exponential fluorescence lifetime estimations in real-time. The combination of high photon throughput and real-time calculation enables advances in applications such as fluorescence lifetime imaging microscopy (FLIM) and time domain fluorescence lifetime activated cell sorting. To demonstrate this, the device is validated in practical bulk sample fluorescence lifetime, FLIM and simulated flow based experiments. Photon throughputs in excess of the excitation frequency are demonstrated for a range of organic and inorganic fluorophores for minimal error in lifetime calculation by CMM (< 5 %).

Yes / Thermal desolvation of poly(N‐isopropylacrylamide) (PNIPAM) in the presence of a low concentration of gold nanoparticles incorporates the nanoparticles resulting in suspended aggregates. By covalently incorporating <1% acenaphthylene into the polymerization feed this copolymer is enabled to be used as a model to study the segmental mobility of the PNIPAM backbone in response to gold nanoparticles both below and above the desolvation temperature, showing that there is a physical conformational rearrangement of the soluble polymer at ultralow nanoparticle loadings, indicating low affinity interactions with the nanoparticles. Thermal desolvation is capable of extracting >99.9% of the nanoparticles from their solutions and hence demonstrates that poly(N‐isopropylacrylamide) can act as an excellent scrubbing system to remove metallic nanomaterial pollutants from solution. / Science Foundation Ireland's ETS. Grant Number: 11/W.I/12085; MRC. Grant Number: MR/N501888/2

In this thesis, the development and implementation of fluorescence lifetime imaging microscopy that integrates time correlated single photon counting (TCSPC) and a confocal microscope will be described. The TCSPC method has high detection efficiency, with a time resolution limited only by the transit time spread of the detector, and directly delivers the decay functions in the time domain. TCSPC can also be used to obtain images that indicate the fluorescence resonance energy transfer (FRET) effect between critical fluorophores, an important method distinguish the difference between binding and co-localization. Estimation of distances between RET fluorophore pairs can also be established. Additionally, the effects of ion concentration, oxygen concentration, pH value, ..etc. can also be revealed.

Advances in nanofabrication have bolstered the development of new optical devices with potential uses ranging from conventional optoelectronics, such as lasers and solar cells, to novel devices, like single photon or entangled photon sources. Quantum encryption of optical communications, in particular, requires devices that couple efficiently to an optical fiber and emit, on demand, indistinguishable photons. With these goals in mind, ultrafast spectroscopy is used to study the electron dynamics in epitaxially grown InAs/GaAs quantum dots (QDs). Quantifying the behavior of these systems is critical to the development of more efficient devices. Studies of two newly developed InGaAs QD structures, quantum dot clusters (QDCs) and QDs embedded in photonic wires, are presented herein. GaAs photonic wires with diameters in the range of 200 to 250 nm support only the fundamental HE11 guided mode. To fully quantify these new systems, the emission dynamics of QDs contained within wires in a large range of diameters are studied. Time correlated single photon counting measurements of the ground state exciton lifetimes are in very good agreement with predicted theoretical values for the spontaneous emission rates. For diameters smaller than 200 nm, QD emission into the HE11 mode is strongly inhibited and non-radiative processes dominate the decay rate. The best small diameter wires exhibit inhibition factors as high as 16, on par with the current state of the art for photonic crystals. The QDCs are the product of a hybrid growth technique that combines droplet heteroepitaxy with standard Stranski-Krastanov growth to create many different geometries of QDs. The work presented in this dissertation concentrates specifically on hexa-QDCs consisting of six InAs QDs around a GaAs nanomound. The first ever spectral and temporal properties of QDs within individual hexa-QDCs are presented. The QDs exhibit narrow exciton resonances with good temperature stability, indicating that excitons are well confined within individual QDs. A distinct biexponential decay is observed even at the single QD level. This behavior suggests that non-radiative decay mechanisms and exciton occupation of dark states play a significant role in the recombination dynamics in the QDCs. / text

High resolution transient/3D imaging technology is of high interest in both scientific research and commercial application. Nowadays, all of the transient imaging methods suffer from low resolution or time consuming mechanical scanning. We proposed a new method based on TCSPC and Compressive Sensing to achieve a high resolution transient imaging with a several seconds capturing process. Picosecond laser sends a serious of equal interval pulse while synchronized SPAD camera's detecting gate window has a precise phase delay at each cycle. After capturing enough points, we are able to make up a whole signal. By inserting a DMD device into the system, we are able to modulate all the frames of data using binary random patterns to reconstruct a super resolution transient/3D image later. Because the low fill factor of SPAD sensor will make a compressive sensing scenario ill-conditioned, We designed and fabricated a diffractive microlens array. We proposed a new CS reconstruction algorithm which is able to denoise at the same time for the measurements suffering from Poisson noise. Instead of a single SPAD senor, we chose a SPAD array because it can drastically reduce the requirement for the number of measurements and its reconstruction time. Further more, it not easy to reconstruct a high resolution image with only one single sensor while for an array, it just needs to reconstruct small patches and a few measurements. In this thesis, we evaluated the reconstruction methods using both clean measurements and the version corrupted by Poisson noise. The results show how the integration over the layers influence the image quality and our algorithm works well while the measurements suffer from non-trival Poisson noise. It's a breakthrough in the areas of both transient imaging and compressive sensing.

No description available.

Quantum computation has been a rich field of study for decades because it promises possible spectacular advances, some of which may run counter to our classically rooted intuitions. At the same time, quantum computation is still in its infancy in both theoretical and practical areas. Efficient quantum algorithms are very limited in number and scope; no real breakthrough has yet been achieved in physical implementations. Grover's search algorithm can be applied to a wide range of problems; even problems not generally regarded as searching problems can be reformulated to take advantage of quantum parallelism and entanglement leading to algorithms which show a square root speedup over their classical counterparts. This dissertation discusses a systematic way to formulate such problems and gives as an example a quantum scheduling algorithm for an R||C_max problem. This thesis shows that quantum solution to such problems is not only feasible but in some cases advantageous. The complexity of the error correction circuitry forces us to design quantum error correction codes capable of correcting only a single error per error correction cycle. Yet, time-correlated errors are common for physical implementations of quantum systems; an error corrected during a certain cycle may reoccur in a later cycle due to physical processes specific to each physical implementation of the qubits. This dissertation discusses quantum error correction for a restricted class of time-correlated errors in a spin-boson model. The algorithm proposed allows the correction of two errors per error correction cycle, provided that one of them is time-correlated. The algorithm can be applied to any stabilizer code, perfect or non-perfect, and simplified the circuit complexity significantly comparing to the classic quantum error correction codes.

No description available.

Nucleic acids, such as DNA, play an essential role in all known forms of life; however, despite their fundamental importance, there is still a significant lack of understanding surrounding their functional behaviour. This thesis explores the structure and dynamics of DNA by employing methods based on fluorescence and through the use of computational calculations. Time-resolved fluorescence experiments have been performed on dinucleotides containing 2-aminopurine (2AP) in various alcohol-water mixtures. 2AP, a fluorescent analogue of the nucleobase adenine, has been used extensively to investigate nucleic acids because of its ability to be incorporated into their structures with minimal perturbation and its high sensitivity to its local environment. Direct solvent effects on 2AP were established through measurements on the free fluorophore. Analysis of the complex fluorescence decays associated with the dinucleotides was challenging but has provided insight into their conformational dynamics. Solvent polarity was found to play a significant role in determining both photophysical and conformational properties in these systems. The complicated fluorescence decay of 2AP in nucleic acids highlights the need for accurate and unbiased analysis methods. Various time-resolved fluorescence analysis methods, including iterative reconvolution and the exponential series method, have been investigated with real and simulated data to obtain an overview of their benefits and limitations. The main outcome of the evaluation is that no single method is preferred in all situations and there is likely to be value in using a combination when there is ambiguity in the interpretation of the results. Regardless of the analysis technique used, the parameterised description of the observed fluorescence decay is meaningless if the underlying physical model is unrealistic. The advance of computational methods has provided a new means to rigorously test the viability of proposed models. Calculations have been performed at the M06-2X/6-31+G(d) level of theory to investigate the stability of 2AP-containing dinucleotides in conformations similar to those observed in the double-helical structure of DNA. The results help to explain the similarity of the time-resolved fluorescence behaviour of 2AP in dinucleotide and DNA systems but also bring to light subtle differences that could perhaps account for experimental discrepancies. The recent emergence of advanced optical microscopy techniques has offered the prospect of being able to directly visualise nucleic acid structure at the nanoscale but, unfortunately, limitations of existing labelling methods have hindered delivery of this potential. To address this issue, a novel strategy has been used to introduce reversible fluorescence photoswitching into DNA at high label density. Photophysical studies have implicated aggregation and energy-transfer as possible quenching mechanisms in this system, which could be detrimental to its future application. The reliability of fluorescence photoswitching was investigated at ensemble and single-molecule level and by performing optical lock-in detection imaging. These developments lay the foundations for improved and sequence-specific super-resolution microscopy of DNA, which could offer new insights into the 3D nanoscale structure of this remarkable biopolymer. In summary, the work presented in this thesis outlines important observations and developments that have been made in the study of the structure and dynamics of nucleic acids.

The purpose of this work is to present the development and validation of a novel method for reconstructing time-dependent, or 4D, cone-beam CT (4DCBCT) images. 4DCBCT can have a variety of applications in the radiotherapy of moving targets, such as lung tumors, including treatment planning, dose verification, and real time treatment adaptation. However, in its current incarnation it suffers from poor reconstruction quality and limited temporal resolution that may restrict its efficacy. Our algorithm remedies these issues by deforming a previously acquired high quality reference fan-beam CT (FBCT) to match the projection data in the 4DCBCT data-set, essentially creating a 3D animation of the moving patient anatomy. This approach combines the high image quality of the FBCT with the fine temporal resolution of the raw 4DCBCT projection data-set. Deformation of the reference CT is accomplished via a patient specific motion model. The motion model is constrained spatially using eigenvectors generated by a principal component analysis (PCA) of patient motion data, and is regularized in time using parametric functions of a patient breathing surrogate recorded simultaneously with 4DCBCT acquisition. The parametric motion model is constrained using forward iterative projection matching (FIPM), a scheme which iteratively alters model parameters until digitally reconstructed radiographs (DRRs) cast through the deforming CT optimally match the projections in the raw 4DCBCT data-set. We term our method FIPM-PCA 4DCBCT. In developing our algorithm we proceed through three stages of development. In the first, we establish the mathematical groundwork for the algorithm and perform proof of concept testing on simulated data. In the second, we tune the algorithm for real world use; specifically we improve our DRR algorithm to achieve maximal realism by incorporating physical principles of image formation combined with empirical measurements of system properties. In the third stage we test our algorithm on actual patient data and evaluate its performance against gold standard and ground truth data-sets. In this phase we use our method to track the motion of an implanted fiducial marker and observe agreement with our gold standard data that is typically within a millimeter.