Computational cytometer based on magnetically modulated coherent imaging and deep learning.

Detecting rare cells within blood has numerous applications in disease diagnostics. Existing rare cell detection techniques are typically hindered by their high cost and low throughput. Here, we present a computational cytometer based on magnetically modulated lensless speckle imaging, which introduces oscillatory motion to the magnetic-bead-conjugated rare cells of interest through a periodic magnetic force and uses lensless time-resolved holographic speckle imaging to rapidly detect the target cells in three dimensions (3D). In addition to using cell-specific antibodies to magnetically label target cells, detection specificity is further enhanced through a deep-learning-based classifier that is based on a densely connected pseudo-3D convolutional neural network (P3D CNN), which automatically detects rare cells of interest based on their spatio-temporal features under a controlled magnetic force. To demonstrate the performance of this technique, we built a high-throughput, compact and cost-effective prototype for detecting MCF7 cancer cells spiked in whole blood samples. Through serial dilution experiments, we quantified the limit of detection (LoD) as 10 cells per millilitre of whole blood, which could be further improved through multiplexing parallel imaging channels within the same instrument. This compact, cost-effective and high-throughput computational cytometer can potentially be used for rare cell detection and quantification in bodily fluids for a variety of biomedical applications

Development of new intelligent autonomous robotic assistant for hospitals

Continuous technological development in modern societies has increased the quality of life and average life-span of people. This imposes an extra burden on the current healthcare infrastructure, which also creates the opportunity for developing new, autonomous, assistive robots to help alleviate this extra workload. The research question explored the extent to which a prototypical robotic platform can be created and how it may be implemented in a hospital environment with the aim to assist the hospital staff with daily tasks, such as guiding patients and visitors, following patients to ensure safety, and making deliveries to and from rooms and workstations. In terms of major contributions, this thesis outlines five domains of the development of an actual robotic assistant prototype. Firstly, a comprehensive schematic design is presented in which mechanical, electrical, motor control and kinematics solutions have been examined in detail. Next, a new method has been proposed for assessing the intrinsic properties of different flooring-types using machine learning to classify mechanical vibrations. Thirdly, the technical challenge of enabling the robot to simultaneously map and localise itself in a dynamic environment has been addressed, whereby leg detection is introduced to ensure that, whilst mapping, the robot is able to distinguish between people and the background. The fourth contribution is geometric collision prediction into stabilised dynamic navigation methods, thus optimising the navigation ability to update real-time path planning in a dynamic environment. Lastly, the problem of detecting gaze at long distances has been addressed by means of a new eye-tracking hardware solution which combines infra-red eye tracking and depth sensing. The research serves both to provide a template for the development of comprehensive mobile assistive-robot solutions, and to address some of the inherent challenges currently present in introducing autonomous assistive robots in hospital environments.Open Acces

System of System Integration for Hyperspectral Imaging Microscopy

Hyperspectral imaging (HSI) has become a leading tool in the medical field due to its capabilities for providing assessments of tissue pathology and separation of fluorescence signals. Acquisition speeds have been slow due to the need to acquire signal in many spectral bands and the light losses associated with technologies of spectral filtering. Traditional methods resulted in limited signal strength which placed limitations on time sensitive and photosensitive assays. For example, the distribution of cyclic adenosine monophosphate (cAMP) is largely undetermined because current microscope technologies lack the combination of speed, resolution, and spectral ability to accurately measure Forster resonance energy transfer (FRET). The work presented in this dissertation assesses the feasibility of integrating excitation-scanning hyperspectral imaging methods in widefield and confocal microscopy as a potential solution to improving acquisition speeds without compromising sensitivity and specificity. Our laboratory has previously proposed excitation-scanning approaches to improve signal-to-noise ratio (SNR) and showed that by using excitation-scanning, most-to-all emitted light at each excitation wavelength band can be detected which in turn, increases the SNR. This dissertation describes development and early feasibility studies for two novel prototype concepts as an alternative excitation-scanning HSI technology that may xvi increase acquisition speeds without compromising sensitivity or specificity. To achieve this, two new technologies for excitation-scanning HSI were conceptually designed: - LED-based spectral illumination for widefield microscopy - Supercontinuum-laser-based spectral illumination for spinning disk confocal microscopy. Next, design concepts were theoretically evaluated and optimized, leading to prototype testing. To evaluate the performance of each concept, prototype systems were integrated with other systems and subsystems, calibrated and feasibility assays were executed. This dissertation is divided into three main sections: 1) early development feasibility results of an excitation-scanning widefield system of systems prototype utilizing LED-based HSI, 2) Excitation-scanning HSI and image analysis methods used for endmember identification in fluorescence microscopy studies, and 3) early development feasibility of an excitation-scanning confocal SoS prototype utilizing a supercontinuum laser light source. Integration and testing results proved initial feasibility of both LED-based and broadband-based SoSs. The LED-based light source was successfully tested on a widefield microscope, while the broadband light source system was successfully tested on a confocal microscope. Feasibility for the LED-based system showed that further optical transmission optimization is needed to achieve high acquisition rates without compromising sensitivity or specificity. Early feasibility study results for the broadband-based system showed a successful proof of concept. Findings presented in this dissertation are expected to impact the fields of cellular physiology, medical sciences, and clinical diagnostics by providing the ability for high speed, high sensitivity microscopic imaging with spectroscopic discrimination

Human activity recognition for the use in intelligent spaces

The aim of this Graduation Project is to develop a generic biological inspired activity recognition system for the use in intelligent spaces. Intelligent spaces form the context for this project. The goal is to develop a working prototype that can learn and recognize human activities from a limited training set in all kinds of spaces and situations. For testing purposes, the office environment is chosen as subject for the intelligent space. The purpose of the intelligent space, in this case the office, is left out of the scope of the project. The scope is limited to the perceptive system of the intelligent space. The notion is that the prototype should not be bound to a specific space, but it should be a generic perceptive system able to cope in any given space within the build environment. The fact that no space is the same, developing a prototype without any domain knowledge in which it can learn and recognize activities, is the main challenge of this project. In al layers of the prototype, the data processing is kept as abstract and low level as possible to keep it as generic as possible. This is done by using local features, scale invariant descriptors and by using hidden Markov models for pattern recognition. The novel approach of the prototype is that it combines structure as well as motion features in one system making it able to train and recognize a variety of activities in a variety of situations. From rhythmic expressive actions with a simple cyclic pattern to activities where the movement is subtle and complex like typing and reading, can all be trained and recognized. The prototype has been tested on two very different data sets. The first set in which the videos are shot in a controlled environment in which simple actions were performed. The second set in which videos are shot in a normal office where daily office activities are captured and categorized afterwards. The prototype has given some promising results proving it can cope with very different spaces, actions and activities. The aim of this Graduation Project is to develop a generic biological inspired activity recognition system for the use in intelligent spaces. Intelligent spaces form the context for this project. The goal is to develop a working prototype that can learn and recognize human activities from a limited training set in all kinds of spaces and situations. For testing purposes, the office environment is chosen as subject for the intelligent space. The purpose of the intelligent space, in this case the office, is left out of the scope of the project. The scope is limited to the perceptive system of the intelligent space. The notion is that the prototype should not be bound to a specific space, but it should be a generic perceptive system able to cope in any given space within the build environment. The fact that no space is the same, developing a prototype without any domain knowledge in which it can learn and recognize activities, is the main challenge of this project. In al layers of the prototype, the data processing is kept as abstract and low level as possible to keep it as generic as possible. This is done by using local features, scale invariant descriptors and by using hidden Markov models for pattern recognition. The novel approach of the prototype is that it combines structure as well as motion features in one system making it able to train and recognize a variety of activities in a variety of situations. From rhythmic expressive actions with a simple cyclic pattern to activities where the movement is subtle and complex like typing and reading, can all be trained and recognized. The prototype has been tested on two very different data sets. The first set in which the videos are shot in a controlled environment in which simple actions were performed. The second set in which videos are shot in a normal office where daily office activities are captured and categorized afterwards. The prototype has given some promising results proving it can cope with very different spaces, actions and activities

NASA SBIR abstracts of 1991 phase 1 projects

The objectives of 301 projects placed under contract by the Small Business Innovation Research (SBIR) program of the National Aeronautics and Space Administration (NASA) are described. These projects were selected competitively from among proposals submitted to NASA in response to the 1991 SBIR Program Solicitation. The basic document consists of edited, non-proprietary abstracts of the winning proposals submitted by small businesses. The abstracts are presented under the 15 technical topics within which Phase 1 proposals were solicited. Each project was assigned a sequential identifying number from 001 to 301, in order of its appearance in the body of the report. Appendixes to provide additional information about the SBIR program and permit cross-reference of the 1991 Phase 1 projects by company name, location by state, principal investigator, NASA Field Center responsible for management of each project, and NASA contract number are included

Automated Detection and Counting of Pedestrians on an Urban Roadside

This thesis implements an automated system that counts pedestrians with 85% accuracy. Two approaches have been considered and evaluated in terms of count accuracy, cost and ease of deployment. The first approach employs the Autoscope Solo Terra, a traffic camera which is widely used to monitor vehicular traffic. The Solo Terra supports an image processing-based detector that counts the number of objects crossing user-defined areas in the captured image. The count is updated based on the amount of movement across the selected regions. Therefore, a second approach has been considered that uses a histogram of oriented gradients (HoG), an advanced vision based algorithm proposed by Dalal et al. which distinguishes a pedestrian from a non-pedestrian based on an omega shape formed by the head and shoulders of a human being. The implemented detection software processes video frames that are streamed from a low-cost digital camera. The frames are divided into sub-regions which are scanned for an omega shape whenever movement is detected in those regions. It has been found that the HoG-based approach degrades in performance due to occlusion under dense pedestrian traffic conditions whereas the Solo Terra approach appears to be more robust. Undercounts and overcounts were encountered using the Solo Terra approach. To combat the disadvantages of both the approaches, they were integrated to form a single system where count is incremented predominantly using the Solo Terra. The HoG-based approach corrects the obtained count under certain conditions. A preliminary prototype of the integrated system has been verified

An On-chip PVT Resilient Short Time Measurement Technique

As the CMOS technology nodes continue to shrink, the challenges of developing manufacturing tests for integrated circuits become more difficult to address. To detect parametric faults of new generation of integrated circuits such as 3D ICs, on-chip short-time intervals have to be accurately measured. The accuracy of an on-chip time measurement module is heavily affected by Process, supply Voltage, and Temperature (PVT) variations. This work presents a new on-chip time measurement scheme where the undesired effects of PVT variations are attenuated significantly. To overcome the effects of PVT variations on short-time measurement, phase locking methodology is utilized to implement a robust Vernier delay line. A prototype Time-to-Digital Converter (TDC) has been fabricated using TSMC 0.180 µm CMOS technology and experimental measurements have been carried out to verify the performance parameters of the TDC. The measurement results indicate that the proposed solution reduces the effects of PVT variations by more than tenfold compared to a conventional on-chip TDC. A coarse-fine time interval measurement scheme which is resilient to the PVT variations is also proposed. In this approach, two Delay Locked Loops (DLLs) are utilized to minimize the effects of PVT on the measured time intervals. The proposed scheme has been implemented using CMOS 65nm technology. Simulation results using Advanced Design System (ADS) indicate that the measurement resolution varies by less than 0.1ps with ±15% variations of the supply voltage. The proposed method also presents a robust performance against process and temperature variations. The measurement accuracy changes by a maximum of 0.05ps from slow to fast corners. The implemented TDC presents a robust performance against temperature variations too and its measurement accuracy varies a few femto-seconds from -40 ºC to +100 ºC. The principle of robust short-time measurement was used in practice to design and implement a state-of-the-art Coordinate Measuring Machine (CMM) for an industry partner to measure geometrical features of transmission parts with micrometer resolution. The solution developed for the industry partner has resulted in a patent and a product in the market. The on-chip short-time measurement technology has also been utilized to develop a solution to detect Hardware Trojans

Scale Stain: Multi-Resolution Feature Enhancement in Pathology Visualization

Digital whole-slide images of pathological tissue samples have recently become feasible for use within routine diagnostic practice. These gigapixel sized images enable pathologists to perform reviews using computer workstations instead of microscopes. Existing workstations visualize scanned images by providing a zoomable image space that reproduces the capabilities of the microscope. This paper presents a novel visualization approach that enables filtering of the scale-space according to color preference. The visualization method reveals diagnostically important patterns that are otherwise not visible. The paper demonstrates how this approach has been implemented into a fully functional prototype that lets the user navigate the visualization parameter space in real time. The prototype was evaluated for two common clinical tasks with eight pathologists in a within-subjects study. The data reveal that task efficiency increased by 15% using the prototype, with maintained accuracy. By analyzing behavioral strategies, it was possible to conclude that efficiency gain was caused by a reduction of the panning needed to perform systematic search of the images. The prototype system was well received by the pathologists who did not detect any risks that would hinder use in clinical routine

Unsupervised modelling of a transitional boundary layer

A data-driven approach for the identification of local turbulent-flow states and of their dynamics is proposed. After subdividing a flow domain in smaller regions, the K -medoids clustering algorithm is used to learn from the data the different flow states and to identify the dynamics of the transition process. The clustering procedure is carried out on a two-dimensional (2-D) reduced-order space constructed by the multidimensional scaling (MDS) technique. The MDS technique is able to provide meaningful and compact information while reducing the dimensionality of the problem, and therefore the computational cost, without significantly altering the data structure in the state space. The dynamics of the state transitions is then described in terms of a transition probability matrix and a transition trajectory graph. The proposed method is applied to a direct numerical simulation dataset of an incompressible boundary layer flow developing on a flat plate. Streamwise-spanwise velocity fields at a specific wall-normal position are referred to as observations. Reducing the dimensionality of the problem allows us to construct a 2-D map, representative of the local turbulence intensity and of the spanwise skewness of the turbulence intensity in the observations. The clustering process classifies the regions containing streaks, turbulent spots, turbulence amplification and developed turbulence while the transition matrix and the transition trajectories correctly identify the states of the process of bypass transition.This work has been supported by: (i) the Madrid Government (Comunidad de Madrid) under the Multiannual Agreement with UC3M in the line of ‘Fostering Young Doctors Research’ (PITUFLOW-CM-UC3M), and in the context of the V PRICIT (Regional Programme of Research and Technological Innovation); (ii) the COTURB project (Coherent Structures in Wall-bounded Turbulence), funded by the European Research Council (ERC), under grant ERC-2014.AdG-669505