A Multi-Method Approach for the Quantification of Surface Amine Groups on Silica Nanoparticles

Title: A Multi-Method Approach for the Quantification of Surface Amine Groups on Silica Nanoparticles
Authors: Sun, Ying
Date: 2019-07-29
Abstract: As nanomaterials continue to garner interest in a wide range of industries and scientific fields, commercial suppliers have met growing consumer demand by readily offering custom particles with size, shape and surface functionality made-to-order. By circumventing the challenging and complex synthesis of functionalized nanoparticles, these businesses seek to provide greater access for the experimentation and application of these nanoscale platforms. In many cases, amine functional groups are covalently attached as a surface coating on a nanoparticle to provide a starting point for chemical derivatization and commonly, conjugation of biomolecules in medical science applications. Successful conjugation can improve the compatibility, interfacing and activity of therapeutic and diagnostic nanomedicines. Amines are amongst the most popular reactive groups used in bioconjugation pathways owing to the many high-yield alkylation and acylation reaction are involved in. For the design of functionalized nanomaterials with precisely tuned surface chemical properties, it is important to develop techniques and methods which can accurately and reproducibly characterize these materials. Quantification of surface functional groups is crucial, as these groups not only allow for conjugation of chemical species, but they also influence the surface charge and therefore aggregation behavior of nanomaterials. The loss of colloidal stability of functionalized nanomaterials can often correspond to a significant if not complete loss of functionality. Thus, we sought to develop multiple characterization approaches for the quantification of surface amine groups. Silica nanoparticles were selected as a model nanomaterial as they are widely used, commercially available, and their surface chemistry has been investigated and studied for decades. Various commercial batches of silica nanoparticles were procured with sizes ranging from 20 – 120 nm. Two colorimetric assays were developed and adapted for their ease-of-use, sensitivity, and convenience. In addition, a fluorine labelling technique was developed which enabled analysis by quantitative solid-state 19F NMR and X-ray photoelectron spectroscopy (XPS). XPS provided data on surface chemical composition at a depth of ≈ 10 nm, which allowed us to determine coupling efficiencies of the fluorine labelling technique and evaluate the reactivity of the two assays. The ensemble of surface-specific quantification techniques was used to evaluate multiple commercial batches of aminated silica and investigate batch-to-batch variability and the influence of particle size with degree of functionalization. In addition, resulting measurements of surface amine content were compared and validated by an independent method based on quantitative solution 1H NMR, which was developed for total functional group content determination. This allowed for us to assess the role of accessibility and reactivity of the amine groups present in our silica particles. Overall, the objective of this study was to develop a multi-method approach for the quantification of amine functional groups on silica nanoparticles. At the same time, we hoped to set a precedent for the development and application of multiple characterization techniques with an emphasis of comparing them on the basis of reproducibility, sensitivity, and mutual validation.
URL: http://hdl.handle.net/10393/39480
CollectionThèses, 2011 - // Theses, 2011 -