Product assurance technology for custom LSI/VLSI electronics

The technology for obtaining custom integrated circuits from CMOS-bulk silicon foundries using a universal set of layout rules is presented. The technical efforts were guided by the requirement to develop a 3 micron CMOS test chip for the Combined Release and Radiation Effects Satellite (CRRES). This chip contains both analog and digital circuits. The development employed all the elements required to obtain custom circuits from silicon foundries, including circuit design, foundry interfacing, circuit test, and circuit qualification

A PCA approach to the object constancy for faces using view-based models of the face

The analysis of object and face recognition by humans attracts a great deal of interest, mainly because of its many applications in various fields, including psychology, security, computer technology, medicine and computer graphics. The aim of this work is to investigate whether a PCA-based mapping approach can offer a new perspective on models of object constancy for faces in human vision. An existing system for facial motion capture and animation developed for performance-driven animation of avatars is adapted, improved and repurposed to study face representation in the context of viewpoint and lighting invariance. The main goal of the thesis is to develop and evaluate a new approach to viewpoint invariance that is view-based and allows mapping of facial variation between different views to construct a multi-view representation of the face. The thesis describes a computer implementation of a model that uses PCA to generate example- based models of the face. The work explores the joint encoding of expression and viewpoint using PCA and the mapping between viewspecific PCA spaces. The simultaneous, synchronised video recording of 6 views of the face was used to construct multi-view representations, which helped to investigate how well multiple views could be recovered from a single view via the content addressable memory property of PCA. A similar approach was taken to lighting invariance. Finally, the possibility of constructing a multi-view representation from asynchronous view-based data was explored. The results of this thesis have implications for a continuing research problem in computer vision – the problem of recognising faces and objects from different perspectives and in different lighting. It also provides a new approach to understanding viewpoint invariance and lighting invariance in human observers

Doctor of Philosophy

dissertationThe importance of lipid bilayers to the structure and function of cellular membranes coupled with their inherent complexity has driven the development of analytical techniques capable of high-throughput investigation of these surfaces. This work describes a continuous flow microspotter (CFM) that was modified to create micropatterned lipid bilayer arrays (MLBAs). This dissertation is divided into four main parts, with the first chapter focusing on the characterization of MLBAs using fluorescence microscopy to ensure bilayer formation and integrity. The individually addressable nature of the CFM was also demonstrated using a multi-ligand array containing ganglioside GM1, dinitrophenyl (DNP) and biotin. A multiple protein-ligand assay was performed using the ligand array to detect three different fluorescently labeled proteins (cholera toxin b (CTb), anti-DNP antibody and NeutrAvidin) from solution simultaneously. The second part of this dissertation concentrates on creating stable MLBAs using a polymerizable lipid, poly(bis-SorbPC) in order to generate a more robust biosensing platform. The poly(lipid) arrays were compared directly to the MLBAs prepared without the polymerizable lipids using fluorescence microscopy to demonstrate their superior stability. A multiple protein-ligand assay was also performed to demonstrate the utility of these arrays and their potential application as a sensor substrate. iv Next, the MLBAs were used to investigate the impact of fifteen different lipid components on small molecule-membrane binding. The lipophilic dye merocyanine 540 (MC540) was used as a model small molecule and its binding was monitored by fluorescence microscopy. These studies demonstrate the potential of using MLBAs to investigate drug membrane interactions while preserving time and cost-effectiveness. Finally, sum-frequency vibrational imaging (SFVI) was developed to provide a surface specific noninvasive, analytical technique capable of monitoring lipid structure and dynamics in a high-throughput manner. The vibrational sensitivity of SFVI was investigated with an asymmetric lipid bilayer patterned by ultraviolet (UV) radiation lithographically. The phase behavior of three different binary mixtures in a MLBA was successfully investigated using SFVI. The SFVI setup had the sensitivity, resolution and field of view required for exploring lipid bilayer properties in an array format. This dissertation presents a new approach for assembling lipid bilayer arrays in combination with a powerful analytical technique to allow exploration of the physical properties of lipid membranes in a high-throughput and noninvasive manner

Entropy is a Simple Measure of the Antibody Profile and is an Indicator of Health Status: A Proof of Concept

abstract: We have previously shown that the diversity of antibodies in an individual can be displayed on chips on which 130,000 peptides chosen from random sequence space have been synthesized. This immunosignature technology is unbiased in displaying antibody diversity relative to natural sequence space, and has been shown to have diagnostic and prognostic potential for a wide variety of diseases and vaccines. Here we show that a global measure such as Shannon’s entropy can be calculated for each immunosignature. The immune entropy was measured across a diverse set of 800 people and in 5 individuals over 3 months. The immune entropy is affected by some population characteristics and varies widely across individuals. We find that people with infections or breast cancer, generally have higher entropy values than non-diseased individuals. We propose that the immune entropy as measured from immunosignatures may be a simple method to monitor health in individuals and populations.The final version of this article, as published in Scientific Reports, can be viewed online at: http://www.nature.com/articles/s41598-017-18469-

RNA Pore Translocation with Static and Periodic Forces: Effect of Secondary and Tertiary Elements on Process Activation and Duration

We use MD simulations to study the pore translocation properties of a pseudoknotted viral RNA. We consider the 71-nucleotide-long xrRNA from the Zika virus and establish how it responds when driven through a narrow pore by static or periodic forces applied to either of the two termini. Unlike the case of fluctuating homopolymers, the onset of translocation is significantly delayed with respect to the application of static driving forces. Because of the peculiar xrRNA architecture, activation times can differ by orders of magnitude at the two ends. Instead, translocation duration is much smaller than activation times and occurs on time scales comparable at the two ends. Periodic forces amplify significantly the differences at the two ends, for both activation times and translocation duration. Finally, we use a waiting-times analysis to examine the systematic slowing downs in xrRNA translocations and associate them to the hindrance of specific secondary and tertiary elements of xrRNA. The findings provide a useful reference to interpret and design future theoretical and experimental studies of RNA translocation

Leveraging Microtechnology to Study Multicellular Microvascular Systems and Macromolecular Interaction

Biological systems are large-scale, complex systems comprised of many hierarchical subsystems interacting physico-chemically in a dynamic and coordinated fashion. The complex interactions of subsystems (in micro-scale) lead to the formation of emergent properties (in macro-scale); these are properties that are not visible if individual subsystems are studied. The inherent high-throughput characteristics of microfabrication technology (microtechnology) along with its ability to manipulate biological species at the micro-scale makes it an ideal tool to elucidate the mechanisms leading to the formation of emergent properties at the macro-scale. In this dissertation, by combining microtechnologies with advanced computational algorithms, we demonstrate system-level analysis of biological systems in development and disease. The abundance of high quality molecular and genetic data along with the drastic increase in computational power resulted in considerable progress in genomics, epigenomics and proteomics, but not for the so-called cellomics as we define it here: high-throughput study of single-cell phenotype and heterotypic cell-cell interaction via micromanipulation and bioinformatics analysis. Lack of high-throughput robust experimental tools is the major roadblock to cellomics. Using microtechnologies, in the context of developmental biology we studied vascular tissue morphogenesis (vasculogenesis). Formation of microvessels is of critical significance in development and for vascularizing newly engineered tissues in regenerative medicine. First, we sought to map the heterogeneous morphodynamic behavior of individual clonal cells in the process of capillary-like structure (CLS) formation (Chapter 2 and 3). Then we looked into deciphering the role of extracellular matrix (ECM) mediated mechanical signals in deriving the process of CLS formation (Chapter 4). In the second half of this thesis, we demonstrated the capabilities of microtechnologies and advanced computational algorithms in tackling the challenging problems in disease: global health diagnostics and cancer drug screening. First, we studied the performance of microfluidic-based diagnostic as a large-scale complex system under real-world constraints (Chapter 5). Then, we present the development of two microfluidic-based platforms to study the heterotypic interaction of cells in both a biomimetic in vitro and a realistic in vivo setting. We developed an implantable construct carrying a densely-packed heterogeneous panel of tumor cells. This platform could ultimately be used to test anti-cancer drug efficacy against a large number of genotypes in an in vivo setting (Appendices A and B). Together, these methods provide a powerful suite of tools for high-throughput analysis of biological species at the micro-scale and could potentially unlock the mysteries behind the emergent properties observed at the macro-scale

Research Experience for Undergraduates Program, 2011

Supported by the National Science Foundation