Search

A significant number of pharmaceuticals supplied to Tanzania are falsified or substandard. A majority of these inadequate pharmaceuticals are medications to treat life-threatening conditions. This problem not only causes mistrust in the healthcare system but also prolonged illness and potentially death for the patients. This calls for the need for the development of a cost-affordable testing kit for falsified and substandard pharmaceuticals in Tanzania. Thin-layer chromatography (TLC) was used as the testing method since it is inexpensive and requires a low skill level to complete. Malaria, human immunodeficiency virus, hypertension, tuberculosis, and diabetes are five of the most prevalent diseases in Tanzania and medications to treat these diseases are commonly falsified or substandard. Doxycycline hyclate, tenofovir disoproxil fumarate, lisinopril dihydrate, pyrazinamide, and dapagliflozin are treatments for the diseases listed above that were used for testing in this project. Five rounds of baseline TLC testing were conducted to determine baseline retention factor (Rf) values for each of the pharmaceuticals. Five rounds of humidity and temperature-controlled TLC testing were conducted for each of the pharmaceuticals to determine if extreme environmental conditions would affect the results. A graphical user interface was developed using MATLAB that contains a library of known Rf values that are referenced when a user enters their experimental values to determine the validity of the pharmaceutical. The user interface, alongside the developed TLC-based testing kit, will reduce overall costs while also effectively determining the iii integrity of a drug. User testing will be conducted, and the kit will be taken to Arusha, Tanzania, to test in the target environment and obtain feedback from scientists at Arusha Technical College.

Abstract: Analytical separations are important methods of identifying and quantifying molecular compounds present in complex sample mixtures. These approaches are popular in biochemistry, medical diagnostics, quality control, and numerous other applications. In these techniques, constituent analytes are separated according to their characteristic physical and chemical properties. Planar chromatography analytical separations leverage the effects of these properties on competing interactions between the compounds, moving liquids, and stationary flat porous solids. Engineered solid-liquid interfaces can improve performance since these interactions occur at the nanoscale. Ultrathin-layer chromatography (UTLC) is a miniature form of planar chromatography in which sample analytes are carried by solvents that wick through < 10 um thick solids with extraordinarily fine pores. The technique achieves fast separations (minutes) over short distances (millimetres to centimetres) with high sensitivity. The strong dependence of UTLC performance on layer microstructure motivates pursuit of new chromatographic media. This dissertation studies UTLC layers produced using glancing angle deposition (GLAD). GLAD is an excellent platform for engineering nanostructured thin films of varied material, porosity, and architecture. It can achieve ~ 5 um thick columnar morphologies well-suited for UTLC that are unattainable or impractical using other techniques. Unique anisotropic media exhibited channel features that strongly influenced analyte migration direction and velocity. Further control of chromatographic behaviours was achieved using post-deposition enhancements. Fluorocarbon reactive ion etching (RIE) selectively modifies film microstructure, increases porosity, and decreases the surface area over which analytes may interact. Atomic layer deposition (ALD) applies extremely thin < 10 nm conformal coatings that produce alternative chromatographic surface chemistries over GLAD UTLC film scaffolds. These investigations required invention of new instrumentation and analysis techniques since conventional planar chromatography equipment is unoptimized for miniaturized GLAD UTLC plates. Approaches to fabricating, utilizing, characterizing, and enhancing nanoengineered GLAD UTLC media are considered in this thesis. The intriguing behaviours described within provide insight into the manner in which the microscopic features of GLAD films impact macroscopic development phenomena. These investigations simultaneously advanced both the capabilities of the UTLC planar chromatography technique and the understanding of GLAD nanostructured thin film materials.

Abstract: Biomolecular separation techniques are an enabling technology that indirectly influence many aspects of our lives. Advances have led to faster analyses, reduced costs, higher specificity, and new analytical techniques, impacting areas such as health care, environmental monitoring, polymer sciences, agriculture, and nutrition. Further development of separations technology is anticipated to follow the path of computing technology such that miniaturization through the development of microfluidics technology, lab-on-a-chip systems, and other integrative, multi-component systems will further extend our analysis capabilities. Creation of new and improvement of existing separation technologies is an integral part of the pathway to miniaturized systems. The work of this thesis investigates molecular separations using porous nanostructured films fabricated by the thin film process glancing angle deposition (GLAD). Structural architecture, pore size and shape, and film density can be finely controlled to produce high-surface area thin films with engineered morphology. The characteristic size scales and structural control of GLAD films are well-suited to biomolecules and separation techniques, motivating investigation into the utility and performance of GLAD films for biomolecular separations. This project consisted of three phases. First, chromatographic separation of dye molecules on silica GLAD films was demonstrated by thin layer chromatography. Direct control of film nanostructure altered the separation characteristics; most strikingly, anisotropic structures provided two-dimensional analyte migration. Second, nanostructures made with GLAD were integrated in PDMS microfluidic channels using a sacrificial etching process; DNA molecules (10/48 kbp and 6/10/20 kbp mixtures) were electrophoretically separated on a microfluidic chip using a porous bed of silicon dioxide vertical posts. Third, mass spectrometry of proteins and drugs in the mass range of 100-1300 m/z was performed using laser desorption/ionization (LDI) on silicon GLAD films, and the influence of film thickness, porosity, structure, and substrate on performance was characterized. The application of GLAD nanostructured thin films to biomolecular separations is demonstrated and validated in this thesis. Chromatographic separation of dye molecules, electrophoretic separation of DNA molecules, and mass spectrometric isolation of small proteins and drug molecules by laser desorption ionization were demonstrated using GLAD films. All three methods yielded promising results and establish GLAD as a potential technology for biomolecular separations.