Advances in Raman and Surface-Enhanced Raman Spectroscopy: Instrumentation, Plasmonic Engineering and Biomolecular Sensing

Raman spectroscopy is a powerful technique for label-free molecular sensing and imaging in various fields. High molecular specificity, non-invasive sampling approach and the need for little or no sample preparation make Raman spectroscopy uniquely advantageous compared to other analytical techniques. However, Raman spectroscopy suffers from the intrinsic limitation of weak signal intensity. Therefore, time-sensitive studies such as diagnosis and clinical applications require improving the throughput of Raman instrumentation. Alternatively, surface-enhanced Raman scattering (SERS) improves the sensitivity by 10^6 to 10^14 times, making the weak Raman intensity no longer a limitation. Nevertheless, it is still a big challenge to engineer plasmonic substrates with high SERS enhancement, good uniformity and reproducibility. This thesis presents advances in: (1) Raman instrumentation towards high-throughput, environmental, biological and biomedical analysis; (2) SERS substrates with high enhancement factor (EF), uniformity and reproducibility; (3) biosensing applications including imaging of cell population and detection of biomolecules towards high time efficiency and sensitivity. In Raman instrumentation, we have built a high-throughput line-scan Raman microscope system and a novel parallel Raman microscope based on multiple-point active-illumination and wide-field hyperspectral data collection. Using the line-scan Raman microscope, we have performed chemical imaging of intact biological cells at the cell population level. We have also demonstrated more flexibility and throughput from the active-illumination Raman microscope in rapid chemical identification and screening of micro and nanoparticles and bacterial spores. Both Raman microscopes have been used to evaluate the large-area SERS uniformity of DC-sputtered gold nanoislands, a low-cost means to fabricate plasmonic substrates. In plasmonic engineering, we have introduced patterned nanoporous gold nanoparticles that feature 3-dimensional mesoporous network with pore size on the order of 10 nm throughput the sub-wavelength nanoparticles. We showed that the plasmonic resonance can be tuned by geometrical engineering of either the external nanoparticle size and shape or the nanoporous network. As an example, we have developed disk-shaped entities, also known as nanoporous gold disks (NPGD) with highly uniform and reproducible SERS EF exceeding 10^8. Label-free, multiplexed molecular sensing and imaging has been demonstrated on NPGD substrates. Using the line-scan Raman microscope and the NPGD substrates, we have successfully developed a label-free DNA hybridization sensor at the single-molecule level in microfluidics. We have observed discrete, individual DNA hybridization events by in situ monitoring the hybridization process using SERS. The advances and promising results presented in this thesis demonstrate potential impact in Raman/SERS imaging and sensing in environmental, biological and biomedical applications.Electrical and Computer Engineering, Department o

2018 Faculty Excellence Showcase, AFIT Graduate School of Engineering & Management

Excerpt: As an academic institution, we strive to meet and exceed the expectations for graduate programs and laud our values and contributions to the academic community. At the same time, we must recognize, appreciate, and promote the unique non-academic values and accomplishments that our faculty team brings to the national defense, which is a priority of the Federal Government. In this respect, through our diverse and multi-faceted contributions, our faculty, as a whole, excel, not only along the metrics of civilian academic expectations, but also along the metrics of military requirements, and national priorities

Computation in Complex Networks

Complex networks are one of the most challenging research focuses of disciplines, including physics, mathematics, biology, medicine, engineering, and computer science, among others. The interest in complex networks is increasingly growing, due to their ability to model several daily life systems, such as technology networks, the Internet, and communication, chemical, neural, social, political and financial networks. The Special Issue “Computation in Complex Networks" of Entropy offers a multidisciplinary view on how some complex systems behave, providing a collection of original and high-quality papers within the research fields of: • Community detection • Complex network modelling • Complex network analysis • Node classification • Information spreading and control • Network robustness • Social networks • Network medicin

15th Annual Undergraduate Student Symposium

The Undergraduate Student Symposium, sponsored by the Farquhar Honors College, presents student projects through presentations, papers, films, and poster displays. The event serves as a “showcase” demonstrating the outstanding scholarship of undergraduate students at NSU. The symposium is open to undergraduate students from all disciplines. Projects cover areas of student scholarship ranging from the experimental and the applied to the computational, theoretical, artistic, and literary. They are taken from class assignments and independent projects. Project presentations can represent any stage in a concept’s evolution, from proposal and literature review to fully completed and realized scholarly work. As in past symposia, the definition of scholarship will be sufficiently broad to include work presented in the biological and physical sciences, the social and behavioral sciences, computer science and engineering, mathematics, arts and humanities, nursing and health care, education, and business. This is the fifteenth annual Undergraduate Student Symposium

Digital ecosystems

We view Digital Ecosystems to be the digital counterparts of biological ecosystems, which are considered to be robust, self-organising and scalable architectures that can automatically solve complex, dynamic problems. So, this work is concerned with the creation, investigation, and optimisation of Digital Ecosystems, exploiting the self-organising properties of biological ecosystems. First, we created the Digital Ecosystem, a novel optimisation technique inspired by biological ecosystems, where the optimisation works at two levels: a first optimisation, migration of agents which are distributed in a decentralised peer-to-peer network, operating continuously in time; this process feeds a second optimisation based on evolutionary computing that operates locally on single peers and is aimed at finding solutions to satisfy locally relevant constraints. We then investigated its self-organising aspects, starting with an extension to the definition of Physical Complexity to include the evolving agent populations of our Digital Ecosystem. Next, we established stability of evolving agent populations over time, by extending the Chli-DeWilde definition of agent stability to include evolutionary dynamics. Further, we evaluated the diversity of the software agents within evolving agent populations, relative to the environment provided by the user base. To conclude, we considered alternative augmentations to optimise and accelerate our Digital Ecosystem, by studying the accelerating effect of a clustering catalyst on the evolutionary dynamics of our Digital Ecosystem, through the direct acceleration of the evolutionary processes. We also studied the optimising effect of targeted migration on the ecological dynamics of our Digital Ecosystem, through the indirect and emergent optimisation of the agent migration patterns. Overall, we have advanced the understanding of creating Digital Ecosystems, the self-organisation that occurs within them, and the optimisation of their Ecosystem-Oriented Architecture

Academic Year 2019-2020 Faculty Excellence Showcase, AFIT Graduate School of Engineering & Management

An excerpt from the Dean\u27s Message: There is no place like the Air Force Institute of Technology (AFIT). There is no academic group like AFIT’s Graduate School of Engineering and Management. Although we run an educational institution similar to many other institutions of higher learning, we are different and unique because of our defense-focused graduate-research-based academic programs. Our programs are designed to be relevant and responsive to national defense needs. Our programs are aligned with the prevailing priorities of the US Air Force and the US Department of Defense. Our faculty team has the requisite critical mass of service-tested faculty members. The unique composition of pure civilian faculty, military faculty, and service-retired civilian faculty makes AFIT truly unique, unlike any other academic institution anywhere

MACHINE LEARNING AND BIOINFORMATIC INSIGHTS INTO KEY ENZYMES FOR A BIO-BASED CIRCULAR ECONOMY

The world is presently faced with a sustainability crisis; it is becoming increasingly difficult to meet the energy and material needs of a growing global population without depleting and polluting our planet. Greenhouse gases released from the continuous combustion of fossil fuels engender accelerated climate change, and plastic waste accumulates in the environment. There is need for a circular economy, where energy and materials are renewably derived from waste items, rather than by consuming limited resources. Deconstruction of the recalcitrant linkages in natural and synthetic polymers is crucial for a circular economy, as deconstructed monomers can be used to manufacture new products. In Nature, organisms utilize enzymes for the efficient depolymerization and conversion of macromolecules. Consequently, by employing enzymes industrially, biotechnology holds great promise for energy- and cost-efficient conversion of materials for a circular economy. However, there is need for enhanced molecular-level understanding of enzymes to enable economically viable technologies that can be applied on a global scale. This work is a computational study of key enzymes that catalyze important reactions that can be utilized for a bio-based circular economy. Specifically, bioinformatics and data- mining approaches were employed to study family 7 glycoside hydrolases (GH7s), which are the principal enzymes in Nature for deconstructing cellulose to simple sugars; a cytochrome P450 enzyme (GcoA) that catalyzes the demethylation of lignin subunits; and MHETase, a tannase-family enzyme utilized by the bacterium, Ideonella sakaiensis, in the degradation and assimilation of polyethylene terephthalate (PET). Since enzyme function is fundamentally dependent on the primary amino-acid sequence, we hypothesize that machine-learning algorithms can be trained on an ensemble of functionally related enzymes to reveal functional patterns in the enzyme family, and to map the primary sequence to enzyme function such that functional properties can be predicted for a new enzyme sequence with significant accuracy. We find that supervised machine learning identifies important residues for processivity and accurately predicts functional subtypes and domain architectures in GH7s. Bioinformatic analyses revealed conserved active-site residues in GcoA and informed protein engineering that enabled expanded enzyme specificity and improved activity. Similarly, bioinformatic studies and phylogenetic analysis provided evolutionary context and identified crucial residues for MHET-hydrolase activity in a tannase-family enzyme (MHETase). Lastly, we developed machine-learning models to predict enzyme thermostability, allowing for high-throughput screening of enzymes that can catalyze reactions at elevated temperatures. Altogether, this work provides a solid basis for a computational data-driven approach to understanding, identifying, and engineering enzymes for biotechnological applications towards a more sustainable world