Thesis (doctoral)--Lunds universitet, Malmö, 1990. / Extra t.p. wih thesis statement inserted. Includes bibliographical references (p. 156-170).

Thesis (doctoral)--Lunds universitet, Malmö, 1990. / Extra t.p. wih thesis statement inserted. Bibliography: p. 156-170.

Thesis advisor: Jianmin Gao / Thesis advisor: Eranthie Weerapana / The imminent threat of antibiotic resistant pathogens that have emerged in clinical settings over the past several decades demands novel solutions in the form of both species- and/or strain-specific diagnostic technologies and treatments. Such new developments would aid in the improved management of bacterial infections by accurate diagnosis and targeted bacterial killing, which would mitigate the continued spread of antibiotic resistance as a result of broad-spectrum antibiotic application The cell surface of bacteria presents a unique opportunity towards development of these modalities, as bacterial cell walls possess both universal and unique features that can be targeted by chemical functionalities without the requirement of cell penetration. This work has sought to take advantage of naturally existing and non-natively installed bacterial cell wall chemical functionalities for which we can develop novel chemoselective chemistries and unique peptides that incorporate those chemical functionalities to enable targeted, biocompatible methods of bacterial labeling and targeting. We initially began these endeavors with the goal of improving upon existing readily reversible iminoboronate chemistry with acetylphenyl boronic acid (APBA), which selectively labels bacteria that contain amine-presenting cell wall lipids (e.g. PE and Lys-PG). In our efforts to improve upon the binding potency of this chemical motif, we synthesized a panel of APBA analogues with varying substituents to modulate amine-binding affinity. We additionally characterized these analogues capacity to form thiazolidinoboronates with free and N-terminal cysteine. Furthermore, we applied an APBA dimer presenting phage library towards identification of potent and selective APBA-presenting peptide binders of 1) a cationic antimicrobial peptide (CAMP) implicated in cancer, human beta defensin 3 (hBD3), and 2) colistin-resistant strains of bacteria that attain their resistance through a variety of different mechanisms. This high-throughput technology afforded identification of peptides that are indeed protein or species/strain selective binders, thus enabling targeted labeling of these important biomolecules. In our continued efforts to identify highly potent and selective bacterial targeting chemistries, we also developed an irreversible chemistry that enables the incorporation of chemical motifs, APBA and semicarbazide, into the cell walls of bacteria through cell wall remodeling mechanisms, which then undergo rapid conjugation with fluorescent and turn-on fluorescent reactive partners. While this alternative approach to bacterial detection requires a primary cell-wall incorporation step, the incorporation and subsequent labeling of these chemical motifs are both highly efficient, which enhances the potency of this bacterial labeling approach The chemical approaches to targeted bacterial labeling herein highlight our ability to develop several species- and strain-selective bioorthogonal chemical probes towards the goal of discovering targeted bacteria binding modalities. Beyond identification of such targeted bacterial binding molecules, we hope to translate these findings into effective, narrow-spectrum antibiotics, which is an endeavor currently being pursued in our laboratory. / Thesis (PhD) — Boston College, 2019. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Isoporous membranes with high pore density and sharp pore size distribution in the micro- and nanoscale providing effective separation are necessary to enable advances in different biological and medical technologies for applications such as detection of cancer cells or pathogens, isolation of circulating tumor cells for blood purification or diagnostic analysis purposes, DNA or proteins sensing, controlled drug delivery or microfluidic devices for organ-on-chip, as well as investigations in plant and bioscience. Hereby, we propose two nanotechnology methods, both combined with lithography and dry reactive ion etching processes, to fabricate a series of polyester membranes with isopores of size in microscale (0.7 to 50 µm) and in nanoscale (300 nm), which demonstrated high porosity and surface area. The membranes fabrication methodologies are environmentally friendly from the aspect that they do not require solvents, and, without water waste characteristics. The membranes are flexible, have excellent chemical and thermal resistance as well as biocompatibility characteristic. All membranes have pore density 10-fold higher than track-etched analogues and exhibit much higher permeance for both microporous and nanoporous membranes. The isoporous system in micron and submicron scales was successfully tested for different applications. The first one was the mild fractionation of organelles of Arabidopsis homogenates. The success indicates that the membranes could be potentially extended to other biological fractionations in substitution of more tedious centrifugation steps. The second successfully demonstrated application is air purification. The membranes had a particulate matter capture efficiency as high as 99 %. In this case, they were coated with silver nanoparticles, which provided high antibacterial effect. The nano-isoporous membranes were successfully demonstrated for nanoparticles sieving. Moreover, by extending the methods to the fabrication of polyimide isoporous membranes, we have proved that they can be easily adapted to other homopolymeric materials that can be chosen according to the needed balance of required stability and economic factors. As far as the resolution is concerned, the achievements we report are among the best combinations of isoporosity with small pore sizes, high pore density and large total active filtration area, currently feasible to fabricate.

The thesis showed preliminary evaluation of novel biodegradable and biocompatible agmatine-containing PAA crosslinkers. Hydrogels fabricated by this crosslinker can obtain controllable stiffness and excellent cell adhesion. The PAA contained thermo-sensitive hydrogel reported here is first employed as filler for depressed defects in rats. Results showed that such hydrogel can be injectable and biocompatible, might become a new material in plastic surgery in the clinic. The thesis also demonstrated a novel macro gels with self-healing capability and biocompatibility. The reversible photodimerization and photocleavage reactivity of coumarin has been successfully imparted to the polymer. / February 2015

No description available.

No description available.

Today’s solid phase microextraction (SPME) is a well known technique that combines knowledge from different fields in an attractive, efficient, and economic way. The development of SPME has seen huge growth since its introduction as a new approach to sample preparation in the early 1990s. The applications of SPME are continuously expanding, and one of the most interesting current aspects consists of applying SPME for fast analysis of biological fluids, both in vitro and in vivo. In spite of this great potential, development of new bio-applications is considerably hindered by the lack of suitable SPME products. The goal of this study is to find SPME coatings that can be utilized for in vivo and in vitro extractions, in direct contact with a biological matrix such as blood or tissue. This thesis presents several effective ways of preparing SPME coatings based on biocompatible polymers and silica-based extractive phases, focusing on their biocompatibility as a must. After fabrication, the proposed coatings are tested for biocompatibility and analytical utility. Finally, some practical applications of the new coatings are presented, such as fast drug analysis and determination of drug plasma protein binding. Six test drugs with different physico-chemical properties are chosen for the investigation: diazepam, verapamil, lorazepam, warfarin, nordiazepam, and loperamide. It is shown that the application of these new SPME fibers for biological sample analysis greatly reduces the time required for sample preparation and limits the exposure of the analytical personnel to potentially infectious biofluids.

Today’s solid phase microextraction (SPME) is a well known technique that combines knowledge from different fields in an attractive, efficient, and economic way. The development of SPME has seen huge growth since its introduction as a new approach to sample preparation in the early 1990s. The applications of SPME are continuously expanding, and one of the most interesting current aspects consists of applying SPME for fast analysis of biological fluids, both in vitro and in vivo. In spite of this great potential, development of new bio-applications is considerably hindered by the lack of suitable SPME products. The goal of this study is to find SPME coatings that can be utilized for in vivo and in vitro extractions, in direct contact with a biological matrix such as blood or tissue. This thesis presents several effective ways of preparing SPME coatings based on biocompatible polymers and silica-based extractive phases, focusing on their biocompatibility as a must. After fabrication, the proposed coatings are tested for biocompatibility and analytical utility. Finally, some practical applications of the new coatings are presented, such as fast drug analysis and determination of drug plasma protein binding. Six test drugs with different physico-chemical properties are chosen for the investigation: diazepam, verapamil, lorazepam, warfarin, nordiazepam, and loperamide. It is shown that the application of these new SPME fibers for biological sample analysis greatly reduces the time required for sample preparation and limits the exposure of the analytical personnel to potentially infectious biofluids.

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 232-255).