Carbon Nanotube-based Optical Sensors for Pharmaceutical Applications
Author | : Daniel Parker Salem |
Publisher | : |
Total Pages | : 221 |
Release | : 2019 |
ISBN-10 | : OCLC:1263579425 |
ISBN-13 | : |
Rating | : 4/5 ( Downloads) |
Download or read book Carbon Nanotube-based Optical Sensors for Pharmaceutical Applications written by Daniel Parker Salem and published by . This book was released on 2019 with total page 221 pages. Available in PDF, EPUB and Kindle. Book excerpt: Semiconducting single-walled carbon nanotubes (SWCNTs) are attractive transducers for biosensor applications due to their unique photostability, single molecule sensitivity, and ease of multiplexing. Sensors can be rendered selective via several detection modalities including the use of natural recognition elements (e.g., proteins) as well as the formation of synthetic molecular recognition sites from adsorbed heteropolymers. However, to date, deployment of SWCNT-based biosensors has been limited. The aim of this thesis was to study the design and development of SWCNT-based optical sensors for analytes relevant to the food and pharmaceutical industries including neurotransmitters, proteins, and metal ions. The research described in this thesis spans several levels of nanosensor development including: i) the fundamental study of SWCNT-polymer interactions and their dependence on solution properties; ii) sensor development using existing detection modalities and the use of mathematical modeling to guide sensor design and interpret data; and iii) the invention of a new sensor form factor enabling long-term sensor stability and point-of-use measurements. Our fundamental work on SWCNT-polymer interactions investigates the influence of polymer structure, SWCNT structure, and solution properties on molecular recognition, using single-stranded DNA as a model polymer system. We find that specific ssDNA sequences are able to form distinct corona phases across SWCNT chiralities, resulting in varying response characteristics to a panel of biomolecule probe analytes. In addition, we find that ssDNA-SWCNT fluorescence and wrapping structure is significantly influenced by the solution ionic strength, pH, and dissolved oxygen in a sequence-dependent manner. We are able to model this phenomenon and demonstrate the implications of solution conditions on molecular recognition, modulating the recognition of riboflavin. These results provide insight into the unique molecular interactions between DNA and the SWCNT surface, and have implications for molecular sensing, assembly, and nanoparticle separations. In addition to our experimental work, we used mathematical modeling to guide sensor design for biopharmaceutical characterization. A mathematical formulation for glycoprotein characterization was developed as well as a dynamic kinetic model to describe the data output by a label-free array of non-selective glycan sensors. We use the formulated model to guide microarray design by answering questions regarding the number and type of sensors needed to quantitatively characterize a glycoprotein mixture. As a second example, we report the design of a novel, diffusion-based assay for the characterization of protein aggregation. Specifically, we design hydrogel-encapsulated SWCNT sensors with a tunable hydrogel layer to influence the diffusion of immunoglobulin G protein species of variable size, and we develop a combined model that describes both the diffusion of analyte and analyte-sensor binding. By measuring the sensor response to a series of well-characterized protein standards that have undergone varying levels of UV stress, we demonstrate the ability to detect protein aggregates at a concentration as low as one percent on a molar basis. Finally, we report the development of a new form factor for optical nanosensor deployment involving the immobilization of SWCNT sensors onto paper substrates. We find that SWCNT optical sensors can be immobilized onto many different paper materials without influencing sensor performance. Moreover, we pattern hydrophobic barriers onto the paper substrates to create 1-dimensional sensor arrays, or barcodes, that are used for rapid, multiplexed characterization of several metal ions including Pb(II), Cd(II) and Hg(II). In addition to providing a new form factor for conducting point-of-use sensor measurements, these findings have the potential to significantly enhance the functionality of SWCNT-based optical sensors by interfacing them with existing paper diagnostic technologies including the manipulation of fluid flow, chemical reaction, and separation.